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physiological roles of Vitamins

          Prepared by;
         Dr. Siham Gritly



              Dr. Siham Gritly    1
glossary
• Vitamin (water soluble vitamin, fat soluble
  vitamin): an organic substance needed in small
  amounts for normal body functions that the body
  cannot synthesize in adequate amounts
• enzyme: a protein that is a catalyst
• cofactor: a small, inorganic or organic substance
  that facilitates enzyme action; includes bothorganic
  coenzymes made from vitamins and inorganic
  substances such as minerals
• Coenzymes are non-protein organic molecules that
  are mostly derivatives of vitamins soluble in water by
  phosphorylation; they bind apoenzyme to proteins to
  produce an active holoenzyme
                         Dr. Siham Gritly               2
• prosthetic group: a cofactor permanently
  associated with the protein, often covalently bound
• holoenzyme: catalytically active enzyme-cofactor
  complex.
• apoenzyme: an enzyme without its cofactor
  enzymatically inactive protein

• FADH2 flavin adenine dinucleotide (reduced form); a
  molecule, central to metabolism, which carries a pair
  of electrons only slightly less energetic than those of
  NADH
• NADH nicotinamide adenine dinucleotide (reduced
  form); a molecule, central to metabolism, which
  carries a pair of high-energy electrons
                         Dr. Siham Gritly                   3
• free radicals: unstable and highly reactive atoms or
  molecules that have one or more unpaired electrons in the
  outer orbital
• 1,25-dihydroxyvitamin D: vitamin D that is made from the
  hydroxylation of calcidiol in the kidneys; the biologically
  active hormone; also called calcitriol or active vitamin D.
• 25-hydroxyvitamin D: vitamin D found in the
• blood that is made from the hydroxylation of cholecalciferol
  in the liver; also called calcidiol
• acetyl CoA; a 2-carbon compound (acetate, or acetic acid)
  to which a molecule of CoA is attached.
• antioxidant: a substance that signifi cantly decreases the
  adverse effects of free radicals on normal physiological
  functions


                           Dr. Siham Gritly                  4
Vitamins
• Vitamins are organic molecules needed for variety of
  biological function within the body.
• The most important role of the vitamins is to serve as
  cofactors (co-enzymes) for enzymatic reactions.
• protein + coenzyme (vitamin)= enzyme
• protein + cofactor (metal ion)= enzyme

• the vitamins cannot be synthesized by mammalian cells
  and, therefore, must be supplied in the diet in small
  quantities (microgram or milligram per day).


                         Dr. Siham Gritly                  5
Coenzyme and vitamins
• Most of the B vitamins are coenzymes and are
  essential in facilitating the transfer of atoms or
  groups of atoms between molecules in the
  formation of carbohydrates, fats, and proteins
• coenzymes: complex organic molecules that
  work with enzymes to facilitate the enzymes’
  activity. Many coenzymes have B vitamins as
  part of their structures.



                       Dr. Siham Gritly                6
• coenzymes is to act as transporters of chemical
  groups from one reactant to another.

• Examples include;
• - nicotinamide adenine dinucleotide
  (NAD), which accepts hydrogen (and gives it
  up in another reaction),
• -ATP, which gives up phosphate groups while
  transferring chemical energy
                     Dr. Siham Gritly           7
The vitamins are of two distinct types, water
            soluble and fat soluble.
Water Soluble Vitamins                        Fat Soluble Vitamins

Thiamin (B1)                        Vitamin A
Riboflavin (B2)
Niacin (B3)                         Vitamin D
Pantothenic Acid (B5)
Pyridoxal, Pyridoxamine,            Vitamin E
Pyridoxine (B6)
Biotin                              Vitamin K
Cobalamin (B12)
Folic Acid

Ascorbic Acid
                           Dr. Siham Gritly                          8
Water soluble vitamins

• -soluble in water, consist of carbon, hydrogen,
  oxygen nitrogen, sulfur, cobalt,

• -deficiency usually occur more than fat soluble
  vitamins

• -Water-soluble vitamins that body cannot store


                      Dr. Siham Gritly              9
• -enter in energy production and in essential
  enzyme system. They help with release of energy
  from carbohydrates, proteins, and fats

• -activate chemical reaction inside the body and
  act as coenzymes

• -excretion in urine through urination

• -the most important water soluble vitamins are B
  complex and vitamin C

                       Dr. Siham Gritly              10
Thiamine or vitamin B1
• thiamine-sulfur containing water soluble
  vitamin of B complex, exist in tissues in the
  active form of Thiamine Pyrophosphate
  (TPP)
• - Thiamine Pyrophosphate (TPP) is essential
  co-enzyme involve in energy extraction and
  cellular process in catabolism of sugar and
  amino acid
• -human and other animal obtain it through diet

                     Dr. Siham Gritly          11
• The majority of thiamine in serum is bound to
  proteins, mainly albumin.
• Approximately 90% of total thiamine in blood
  is in erythrocytes (red blood cell).




                    Dr. Siham Gritly          12
• Thiamin is rapidly converted to its active form,
  thiamin pyrophosphate, TPP, in the brain and liver
  by a specific enzyme;-
• thiamin diphosphotransferase.
• TPP is necessary as a cofactor for the;-
• 1-pyruvate dehydrogenase (PDH) and
• 2-α-ketoglutarate dehydrogenase catalyzed
  reactions associated with the TCA cycle

• 3-transketolase catalyzed reactions of the pentose
  phosphate pathway
                       Dr. Siham Gritly            13
Thiamin functions
• -the main function of thiamine is its role in
  metabolic reaction acting as co-enzyme for
  energy and carbohydrate metabolism

• -its deficiency in tissues affect energy
  metabolism and thus affect nerve and cardiac
  functions


                      Dr. Siham Gritly            14
TPP is necessary as a cofactor for the important
      enzyme pyruvate dehydrogenase (PDH),
   α-ketoglutarate dehydrogenase and transketolase
• 1-Pyruvate dehydrogenase is the key enzyme
  in CHO metabolism to complete oxidation (via
  the TCA cycle)
• TPP participate in catalyzing oxidative
  decarboxylation of pyruvate, to form acetyl-
  CoA in citric acid cycle, where a carboxyl group
  is removed from a compound and released as
  CO2.
                       Dr. Siham Gritly               15
An example is the conversion of pyruvate to acetyl-
 CoA, which is irreversible, during CHO metabolism

• Oxidative decarboxylation reactions are
  oxidation reactions in which a carboxylic
  group is removed, forming CO2




                       Dr. Siham Gritly                16
• 2-α-ketoglutarate dehydrogenase -thiamine
  involved in decarboxylation of alph
  ketoglutrate to succinate in krebs cycle by the
  emzyme α-ketoglutarate dehydrogenase
• -deficiency of thiamine lead to accumulation
  of pyruvate in the blood thus affect peripheral
  nervous system and heart


                      Dr. Siham Gritly              17
• 3-transketolase; catalyzed reactions of the
  pentose phosphate pathway
• oxidative phase, NADPH is generated when
  glucose 6-phosphate is oxidized to ribose 5-
  phosphate.




                     Dr. Siham Gritly            18
deficiency of thiamin

• -two different diseases may result as
  deficiency of thiamin
• 1-Beri Beri (wet and dry beri beri) Usually beri
  beri diseases result due to long term deficiency
  and high intake of carbohydrates

• -Korsakoff syndrome (psychosis)


                      Dr. Siham Gritly           19
• Wernicke-Korsakoff syndrome; This disease
  is most commonly found in chronic alcoholics
  due to their poor dietetic lifestyles.
• Wernicke-Korsakoff syndrome is
  characterized by acute encephalopathy (brain
  dysfunction) followed by chronic impairment
  of short-term memory




                    Dr. Siham Gritly         20
• - Wet beriberi is associated with mental
  confusion, muscular atrophy, edema, tachycardia,
  caridomegaly and congestive heart failure in
  addition to peripheral neuropathy (is damage to
  nerves of the peripheral nervous system
• - Dry beriberi is characterized principally by
  peripheral neuropathy. Muscle become waste and
  week, difficult walking, patient become bedridden
  and may die.

                      Dr. Siham Gritly            21
Beriberi is a disease caused by a deficiency of thiamine
     (vitamin B1) that affects many systems of the
body, including the muscles, heart, nerves, and digestive
                         system




                         Dr. Siham Gritly              22
Riboflavin, vitamin B2
• Active form of riboflavin is Riboflavin Phosphate
• It is the central component of the cofactor FAD and
  FMN, and therefore required for energy metabolism

• vitamin B2 is required for a wide variety of cellular
  processes transferring oxygen from plasma to the
  tissues.

• It plays a key role in energy metabolism, and for the
  metabolism of fats, ketone bodies, carbohydrates and
  proteins.

                         Dr. Siham Gritly                 23
• Vitamin B2, or riboflavin is an intermediary
  the transfer of electrons in the cellular
  oxidation-reduction reactions which generate
  energy from protein, carbohydrate and fat FAD
  and FMN.
• The riboflavin coenzymes are also important
  for the transformation of vitamin B6 and folic
  acid into their respective active forms, and for
  the conversion of tryptophan into niacin.

                      Dr. Siham Gritly           24
• Synthesis of these two cofactors occurs in a
  two step process.
• 1-FMN is synthesized from riboflavin via the
  ATP-dependent enzyme riboflavin kinase
  (RFK).
• RFK introduces a phosphate group onto the
  terminal hydroxyl of riboflavin.



                    Dr. Siham Gritly             25
• 2-FMN is then converted to FAD via the
  attachment of AMP (derived from ATP) though
  the action of FAD pyrophosphorylase




                   Dr. Siham Gritly         26
Deficiency of riboflavin

• In humans, signs and symptoms of riboflavin
  deficiency
• -include cracked and red lips, inflammation of the
  lining of mouth and tongue, mouth ulcers, cracks
  at the corners of the mouth (Angular
  cheilitis), and a sore throat.
• -A deficiency may also cause dry and scaling
  skin, fluid in the mucous membranes, and iron-
  deficiency anemia. The eyes may also become
  bloodshot, itchy, watery and sensitive to bright
  light.

                       Dr. Siham Gritly            27
Riboflavin Deficiency




Riboflavin Deficiency                        Riboflavin Deficiency
(Cheilosis)                                  (Glossitis
                          Dr. Siham Gritly                           28
Niacin Vitamin B3
nicotinic acid, nicotinamide, niacinamide
• Niacin (nicotinic acid and nicotinamide) is also
  known as vitamin B3.
• Both nicotinic acid and nicotinamide can
  serve as the dietary source of vitamin B3.
• Niacin is required for the synthesis of the
  active forms of vitamin B3, nicotinamide
  adenine dinucleotide (NAD+) and nicotinamide
  adenine dinucleotide phosphate (NADP+).

                      Dr. Siham Gritly           29
• NADH, NAD+, NADP+ and NADPH which are
  coenzymes found in all living cells.
• NAD+ and NADP+ are oxidizing agents.(loss of
  electron)
• NADH and NADPH are reducing agents.(gain of
  electron)
reactions involved dehydrogenase enzymes
electron transport and hydrogen carrier involved
  in fats, carbohydrates and protein metabolism

                     Dr. Siham Gritly          30
Niacin functions
 Role of NAD+ in oxidation-reduction reactions

1-reaction of transport hydrogen atom from one
  part to another, occur in mitochondria and
  cytoplasm of the cells –oxidative reactions of
  NAD------NADH
*glycolysis -------glyceraldehyde 3P to 1,3
  diphosphglycerate
*oxidative decarboxylation of pyruvate to lactate


                     Dr. Siham Gritly            31
oxydation of acetyl Co A in TCA cycle
-malate to oxaloacetate
-glutamate to α ketoglutrate
*β oxidation of fatty acid

2-NAD----dehydrogenase for catabolism of
  vitamin B6 pyridoxal to its excretory product
  (pyridoxin acid)
                     Dr. Siham Gritly             32
3-NADPH (reduced form) involved in;
Fatty acid synthesis
Cholesterol synthesis
Deoxy-ribonucleotide molecules (DNA)

4-NADPH--- convert folate to dihydrofolate
  (DHF) and synthesis of 5 methyl-
  tetrahydrofolate the active form of folic acid
                      Dr. Siham Gritly             33
niacin deficiency

• Severe deficiency of niacin in the diet causes the
  disease pellagra characterized by three Ds;
Diarrhea, loss of fluids

Dermatitis, hyperpigmentation, thickening of the
  skin, inflammation of the mouth and
  tongue, digestive disturbances,

Dementia, (mental symptoms) such as irritability, poor
  concentration, anxiety, fatigue, restlessness, apathy, a
  nd depression          Dr. Siham Gritly                 34
Pellagra
niacin deficiency




     Dr. Siham Gritly   35
Pellagra
niacin deficiency




     Dr. Siham Gritly   36
Pyridoxine
                  vitamin B6
• Pyridoxal,
•  pyridoxamine
• Pyridoxine
•  are collectively known as vitamin B6.
• The three forms equal vital activities in their
  active forms
• found in different types of food such as; Wheat
  germ, Sunflower seeds, Dry
  Soybeans, Walnuts, Soybean flour Lentils Brown
  rice peas Bananas, Chicken, white fish, Potatoes

                      Dr. Siham Gritly               37
• All three compounds are efficiently converted
  to the biologically active form of vitamin
  B6, pyridoxal phosphate (PLP).
• -pyridoxal phosphate
• -pyridoxine phosphate
• -pyridoxamine phosphate
• This conversion is catalyzed by the ATP
  requiring enzyme, pyridoxal kinase.
• Pyridoxal kinase requires zinc for full activity
  thus making it a metaloenzyme.
                      Dr. Siham Gritly           38
• Pyridoxal phosphate functions as a cofactor in
  enzymes involved in transamination reactions
  required for the synthesis and catabolism of
  the amino acids
• Act as co-enzyme needed in amino acid
  metabolism such as conversion of essential
  amino acid tryptophan to vitamin niacin


                     Dr. Siham Gritly              39
• Also it function in glycogenolysis as a cofactor for
  glycogen phosphorylase

• Vitamin B6 is involved in over 100 metabolic reactions
  in the body, including the production of energy and
  hemoglobin, a protein in red blood cells. Intakes below
  the DRI can hurt performance.

• Deficiencies of vitamin B6 are rare and usually are
  related to an overall deficiency of all the B-complex
  vitamins
                          Dr. Siham Gritly                40
• Factors which reduce Vitamin B6 absorption
• Exposure of Vitamin B6 containing foods to
  ultraviolet light
• Cooking
• Exposure to alkaline pH
• Food processing destroys up to 90% of
  Vitamin B6 content in food


                    Dr. Siham Gritly           41
• Factors which increase Vitamin B6 excretion
• Smoking
• Excess alcohol
• Excessive tea /coffee caffeinated drinks
  consumption
• Use of hormonal contraception
• Use of drugs such as diuretics,
• Excessive protein consumption

                    Dr. Siham Gritly            42
Pantothenic acid

• Pantothenic acid is used in the synthesis of co-
  enzyme A (CoA).
• This coenzyme is formed when the vitamin
  combines with a derivative of ADP and the amino
  acid cysteine.

• Coenzyme A may act as an acyl group carrier to
  form acetyl-CoA and other related compounds;
  this is a way to transport carbon atoms within the
  cell.
                       Dr. Siham Gritly                43
• CoA is also important in the biosynthesis of
  many important compounds such as fatty
  acids, cholesterol.
• CoA is important in energy metabolism for
  pyruvate to enter the Kerbs cycle or
  tricarboxylic acid cycle (TCA cycle) as acetyl-
  CoA,
• and for α-ketoglutarate to be transformed to
  succinyl-CoA in the cycle.

                     Dr. Siham Gritly           44
Deficiency of Pantothenic Acid

• deficiency of pantothenic acid in rats leads to
  elevated serum concentrations of triglycerides
  and non-esterified fatty acids, reflecting
  impaired β- oxidation.
• with B-oxidation would have an effect on fat
  use. Co-A is also necessary in CHO
  metabolism, as it is a part of acetyl-CoA



                      Dr. Siham Gritly              45
Folic acid
                (pteroylglutamic acid)
• The folates are a group of heterocyclic compounds
  consisting of a pteridine ring structure linked to para-
  aminobenzoic acid (PABA) that forms pteroic acid.

• Pteridine is a group of organic compounds having
  two fused six-member rings each containing two
  nitrogen atoms and four carbon atoms.
• One of the rings is a pyrimidine, the other a pyrazine.




                         Dr. Siham Gritly                46
Folic acid (pteroylglutamic acid) is composed of three large sub-
components. 1-pteridine ring,2- para-amino benzoic acid, and 3-
glutamic acid. Glutamic acid is an amino acid that the body can
actually synthesize by itself and is found in proteins. Folic acid
gets its name from the Latin word folium meaning "leaf", since
it's found in many leafy plants.




                             Dr. Siham Gritly                    47
• The number of glutamate molecules affects the
  absorption and metabolism of folate or folic
  acid in the body.




                    Dr. Siham Gritly          48
active form of folic acid is tetrahydrofolate
Chemical structure of THF. The N5 and N10-nitrogen
 atoms that can carry one-carbon functional groups




                     Dr. Siham Gritly            49
Pteroylglutamate (folic acid)
Polyglutamate is the storage form of folic acid in the
                        liver
• Folic acid is reduced within cells (principally
  the liver where it is stored) to;
  tetrahydrofolate (THF also H4folate) through
  the action of dihydrofolate reductase
  (DHFR), an NADPH-requiring enzyme.

• When stored in the liver or ingested folic acid
  exists in a polyglutamate form

                       Dr. Siham Gritly              50
• Deficiency causes megaloblastic anemia as for
  vitamin B12 deficiency.
• The inability to synthesize DNA during
  erythrocyte maturation leads to abnormally large
  erythrocytes termed macrocytic anemia

• Folic acid is important in preventing neuraltube
  defects (NTDs) in the developing human fetus.

                       Dr. Siham Gritly              51
megaloblastic macrocytic anemia




            Dr. Siham Gritly      52
Vitamin B12 cyanocobalamin
• Vitamin B12 is the name for a class of related
  compounds that have the vitamin activity. These
  compounds contain the rare element cobalt.
• Humans can not synthesis B12 and must obtain it from
  diet. Enzymes that catalyze certain rearrangement
  reaction required B12 or its derivatives.
• Vitamin B12 is synthesized exclusively by
  microorganisms and is found in the liver of animals
  bound to protein as methycobalamin or
  5'-deoxyadenosylcobalamin.

                       Dr. Siham Gritly              53
• The vitamin must be hydrolyzed from protein
  in order to be active.
• Hydrolysis occurs in the stomach by gastric acids
  or the intestines by trypsin following consumption
  of animal meat.
• The vitamin is then bound by intrinsic factor, a
  protein secreted by parietal cells of the
  stomach, and carried to the ileum where it is
  absorbed.
• Following absorption the vitamin is transported
  to the liver in the blood bound to transcobalamin
  II.
                      Dr. Siham Gritly             54
• Vitamin B12 is involved in a number of body
  processes, but is mainly;
• formation to red blood cell production,
• nervous system function,
• sperm production,
• normal growth
• the proper function of the immune system.

                    Dr. Siham Gritly            55
There are only two clinically significant reactions in
   the body that require vitamin B12 as a cofactor.
• 1- During the catabolism of fatty acids with an
  odd number of carbon atoms and the amino acids
  valine, isoleucine and threonine the resultant
  propionyl-CoA is converted to succinyl-CoA for
  oxidation in the TCA cycle.
• One of the enzymes in this
  pathway, methylmalonyl-CoA mutase, requires
  vitamin B12 as a cofactor in the conversion of
  methylmalonyl-CoA to succinyl-CoA.
• The 5'-deoxyadenosine derivative of cobalamin is
  required for this reaction.

                        Dr. Siham Gritly                  56
• 2-The second reaction requiring vitamin B12
  catalyzes the conversion of homocysteine to
  methionine and is catalyzed by methionine
  synthase.
• This reaction results in the transfer of the
  methyl group from N5-methyltetrahydrofolate
  to hydroxycobalamin generating
  tetrahydrofolate (THF) and methylcobalamin
  during the process of the conversion

                    Dr. Siham Gritly             57
Deficiencies of B12
     Pernicious anemia is a megaloblastic anemia
        resulting from vitamin B12 deficiency
• The liver can store up to six years vitamin
  B12, therefore deficiencies in this vitamin are
  rare.

• Pernicious anemia is a megaloblastic anemia
  resulting from vitamin B12 deficiency that
  develops as a result a lack of intrinsic factor in
  the stomach leading to malabsorption of the
  vitamin.
                       Dr. Siham Gritly             58
• Pernicious anemia characterized by
  abnormally large and immature red blood
  cells.
• Other symptoms include muscle weakness and
  irreversible neurological damage

• The anemia results from impaired DNA
  synthesis due to a block in purines and
  thymidine biothynthesis.
                     Dr. Siham Gritly       59
Biotin
• Biotin, one of the water soluble B-
  vitamins, occurs in 8 different forms but only
  one of these, D-biotin, is found in nature and
  has full vitamin activity

• It is water soluble and important in the
  metabolism of fatty acids and the amino acid
  Leucine

                     Dr. Siham Gritly              60
• Biotin in its coenzyme form participates in
  numerous reactions involved in the metabolism
  of fat and CHO
• involved in carboxylation reactions, e.g. acetyl-
  CoA carboxylase and pyruvate carboxylase.

• participates in the entry of certain carbon
  skeletons from amino acids into the energy-
  yielding pathways, as well as in DNA synthesis.
                       Dr. Siham Gritly               61
• Biotin is found in numerous foods and also is
  synthesized by intestinal bacteria and as such
  deficiencies of the vitamin are rare.
• Deficiencies are generally seen only after long
  antibiotic therapies which deplete the intestinal
  fauna or following excessive consumption of raw
  eggs.
• The latter is due to the affinity of the egg white
  protein, avidin, for biotin preventing intestinal
  absorption of the biotin.
                       Dr. Siham Gritly                62
Deficiency is rare, but can result in:Anorexia Nausea
Vomiting Dermatitis

• Symptoms that may appear if biotin is deficient
  are extreme exhaustion, drowsiness, muscle
  pain, loss of appetite, depression, and grayish skin
  color.
• Some of the richest sources of biotin are
  tomatoes, romaine lettuce, and carrots. Additional
  sources include
  onions, cabbage, cucumber, cauliflower, mushroo
  ms, peanuts, almonds, walnuts, oat
  meal, bananas, raspberries, strawberries, soy, egg
  yolk, and cow and goat milk.

                       Dr. Siham Gritly              63
Vitamin C Ascorbic Acid
     Main physiological roles of vitamin C
• Vital component of all body cells
• Essential for manufacture of collagen, needed
  for healthy connective tissue, skin, bones and
  vascular system
• Powerful Antioxidant
• Stimulates white blood cells and antibody
  production
• Required for proper wound healing and tissue
  regeneration
                     Dr. Siham Gritly              64
• Assists iron absorption
• powerful effects on the production of
  important chemicals for the control of
  hormones and brain function.
• plays a vital role in the immune system
• It is a key component of collagen
• Vitamin C also helps to benefit the skin, teeth,
  and bones.
                      Dr. Siham Gritly               65
• Deficiency leads to a disease called Scurvy.
• Scurvy is a disease that affects the blood
  vessels, skin, and the body’s healing
  process, resulting in anemia, hemorrhaging of
  the skin, and gum disease (gingivitis).
• Vitamin C is found in most plants and animals



                     Dr. Siham Gritly             66
• People requiring additional Vitamin C.
• some specific groups who are likely to benefit
  more ;
• People with heart disease (angina, heart
  attack, "hardened arteries", coronary artery
  disease, other vascular disease, high blood
  pressure)
• Diabetics
• Those with poorly healing wounds (such as leg
  ulcers)
• People with skin problems
                      Dr. Siham Gritly             67
Examples of Coenzymes and Vitamins
     reference; Cooper GM; The Central Role of Enzymes as
BiologicalCatalysts The Cell: A Molecular Approach. 2nd edition

Coenzyme            Related vitamin             Chemical reaction
NAD+, NADP+         Niacin                      Oxidation-reduction
FAD                 Riboflavin (B2)             Oxidation-reduction
Thiamine            Thiamine (B1)               Aldehyde group
pyrophosphate                                   transfer
Coenzyme A          Pantothenate                Acyl group transfer
Tetrahydrofolate    Folate                      Transfer of one-
                                                carbon groups
Biotin              Biotin                      Carboxylation
Pyridoxal           Pyridoxal (B6)              Transamination
phosphate                    Dr. Siham Gritly                      68
Fat soluble vitamins
• Fat soluble vitamins dissolve within the body’s fat
  cells and are usually found in fats and fatty foods.

• If they are not needed immediately, the body will
  store fat soluble vitamins for later use in the liver
  and fatty tissues

• fat soluble vitamins do not need to be consumed
  as frequently as water soluble vitamins to ensure
  proper functioning of the body’s cells.

                        Dr. Siham Gritly              69
Vitamin A
• Vitamin A consists of three biologically active
  molecules,
• 1-retinol, (hydroxyl) involved in vision
• 2- retinal (aldehyde) involved in vision
• 3-retinoic acid. (carboxyl)

• Importance for cellular differentiation (regulate gene
  expression)

• Each of these compounds are derived from the plant
  precursor molecule, β-carotene (a member of a family
  of molecules known as carotenoids).

                          Dr. Siham Gritly                 70
• Beta-carotene, which consists of two molecules of
  retinal linked at their aldehyde ends, is also
  referred to as the provitamin form of vitamin A.
• Vitamin A is found in dark green and yellow
  vegetables and yellow fruits, such as
  broccoli, spinach, turnip
  greens, carrots, squash, sweet
  potatoes, pumpkin, cantaloupe, and
  apricots, and in animal sources such as
  liver, milk, butter, cheese, and whole eggs.
                      Dr. Siham Gritly            71
Absorption, transport and storage
• Ingested β-carotene is cleaved in the lumen of the
  intestine by β-carotene dioxygenase to yield
  retinal.
• Retinal is reduced to retinol by retinaldehyde
  reductase, an NADPH requiring enzyme within
  the intestines.
• Retinol is esterified to palmitic acid and delivered
  to the blood via chylomicrons. The uptake of
  chylomicron by the liver results in delivery of
  retinol to this organ for storage as a lipid ester
  within lipocytes (adipose tissues).
                        Dr. Siham Gritly             72
• Transport of retinol from the liver to extrahepatic
  tissues occurs by binding of hydrolyzed retinol to
  aporetinol binding protein (RBP).
• the retinol-RBP complex is then transported to the
  cell surface within the Golgi and secreted. Within
  extrahepatic tissues retinol is bound to cellular
  retinol binding protein (CRBP).
• Plasma transport of retinoic acid is
  accomplished by binding to albumin
                       Dr. Siham Gritly             73
Vitamin A functioning as vitamin and hormone

• retinol and retinoic acid with in the cell bind to
  specific receptor present in the nucleolus of
  tissues
• This receptor-vitamin complex interact with
  several genes that involved in growth and cell
  differentiation thus affect expression of genes
• cell differentiation is the process by which
  immature cells develop specific functions
  different from those of the original that are
  characteristic of their mature cell type.
                        Dr. Siham Gritly               74
Vision and Vitamin A
• the process of vitamin A in vision known as
  Rhodopsin cycle or Ward’s visual cycle the
• Photoreception in the eye is the function of
  two specialized cell types located in the retina;
• Rods
• Cones
• Both rod and cone cells located in the retina
  contain a photoreceptor pigment in their
  membranes and vitamin A is a component of
  these pigments
                      Dr. Siham Gritly            75
• the rod;- The opsin of rod cells is called
  Rhodopsin (visual purple) consist of 11-cis retinal
  bound to protein opsin (vision in dim light)
• Rhodopsin absorbs light, 11-cis retinal is
  converted to all trans retinal
• The isomerization act on the conformation change
  in the protein opsin
• This process lead to generate nerve impulse that
  transmitted to brain through the optic nerve
                       Dr. Siham Gritly             76
• This is followed by dissociation of the trans
  retinal from opsin
• The trans retinal is immediately isomerised by
  the enzyme isomerase to 11-cis retinal
• 11-cis retinal combines with opsin to
  regenerate rhodopsin and complete the vision
  cycle


                     Dr. Siham Gritly              77
• cone cells, contain colour
  pigments, *porphyropsin (red)
• *Iodopsin (green)
• *Cyanopsin (blue)
• The pigments are converted to trans retinal and
  the protein opsin is released
• The reaction stimulate the nerve impulse thus
  the brain red the colour

                     Dr. Siham Gritly           78
Dr. Siham Gritly   79
Vitamin A Deficiency
• Vitamin A is stored in the liver and deficiency of
  the vitamin occurs only after prolonged lack of
  dietary intake.
• The earliest symptoms of vitamin A deficiency
  are night blindness.
• Additional early symptoms include follicular
  hyperkeratinosis, increased susceptibility to
  infection and cancer and anemia equivalent to
  iron deficient anemia.
• Prolonged lack of vitamin A leads to
  deterioration of the eye tissue through progressive
  keratinization of the cornea, a condition known as
  xerophthalmia.
                       Dr. Siham Gritly             80
The earliest symptoms of vitamin A deficiency ;-
*impaired dark adaptation –night blindness (nyctalopia)
*poor vision in dim light
*xerophthalmia
The first stage of xerophthalmia is conjunctival xerosis
Later Bitot’s spots form (keratinization of epithelial
  cells)
A deficiency progresses degenerative changes of retina
  occurs (keratomalcia)

                        Dr. Siham Gritly               81
keratomalcia
Softening and drying and ulceration of the cornea resulting from
    vitamin A deficiency developed in the cornea that lead to
                           blindness




                            Dr. Siham Gritly                   82
Xerophthalmia
Xerophthalmia is a severe drying of the eye surface caused by
                a malfunction of the tear glands.
  it occurs most commonly because of decreased intake or
absorption of vitamin A. Symptoms include night blindness
and eye irritationthe eyes being very dry, there is a loss of luster on
                             their surface
                                      .




Ulceration and necrosis
developed in the cornea
that lead to blindness
                               Dr. Siham Gritly                       83
Vitamin D cholecalciferol

• Vitamin D is known as the sunshine vitamin
  because exposure to sunlight prompt the
  body’s cells to start producing it.
• Vitamin D2 functions as a steroid hormone and
  vitamin
• regulate calcium and phosphorous homeostasis
• dairy products (such as eggs, milk and
  butter), fatty fish and fish oils are all good
  sources of vitamin D.
                     Dr. Siham Gritly          84
Vitamin D comes in many forms, but the two
most important in the diet arel
• 1-plant sterol ergosterol which isolated from
  plant and by commercial irradiation light UV
  converted to vitamin D2 or ergocalciferol not
  found in human tissues

• 2-animal sources or naturally produced called
  vitamin D3 or cholecalciferol.


                     Dr. Siham Gritly             85
Formation of vitamin D3 in the skin

• The naturally found vitamin D3 cholecalciferol is
  the form obtained either from animal sources or
  made in the skin by the action of ultraviolet light
  from the sun on 7-dehydrocholesterol
• 7-dehydrocholesterol found in animal tissues
  synthesized in the sebaceous glands of the skin
  and secreted into the skin surface
• During exposure to sunlight 7-dehydrocholesterol
  forming pre-cholecalcefirol (previtamin D3)
                       Dr. Siham Gritly             86
activation of vitamin D must be achieved
through;
• 1-Liver
• 2-kidneys
• In the Liver;- cholecalciferol fuses into the blood
  carried by D-binding protein (DBP) known as
  transcalciferin to the liver
• By the action of liver enzyme 25-hydroxylase
  hydroxylate cholecaciferol at carbon 25 to form 25-
  OH cholecalciferol/D3
• The activity of this enzyme related to the
  concentration of vitamin D
• 25-hydroxylase also found in lungs, intestine and
                           Dr. Siham Gritly             87
  kidneys
• In the kidneys;-a second hydroxylation of 25-OH D3
  (25-hydroxylcalcefirol) occur at position 1
• by the action of enzyme;-
• 1-hydroxylase, 25-cholecalsiferol hydrolyized to
  1,25-(OH)2 cholecalecalciferol or known as
  (calcitriol ) the active form of vitamin D
• By the transporter DBP which is the major protein
  in the blood transported the active form calcitriol
  (1,25-(OH)2 cholecalciferol) to the target tissues

                       Dr. Siham Gritly                88
• Active form of the hormone
  The biologically active form of the hormone is;
  1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also
  called 1,25-dihydroxycholecalciferol or
  calcitriol).




                     Dr. Siham Gritly           89
• The activity of 1-hydroxylase is influenced by
• -parathyroid hormone
• -low plasma concentration
• -The concentration of 1,25
  hydoxycholecaciferol- high concentration
  inhibit the enzyme activity,- low concentration
  stimulate it
• Low intake of phosphours
                     Dr. Siham Gritly           90
• 25-(OH)D3 can also be hydroxylated at the 24
  position by a specific D3-24-hydroxylase in the
  kidneys, intestine, placenta and cartilage




                     Dr. Siham Gritly           91
1,25-dihydroxcholecaliciferol D3 formation
                  Tissue cholesterol
                                    ↓
                                 Sun
                                      ↓
                 7-dehydrocholesterol
                             Plasma
                 Cholecaliciferol D3
                                     ↓
                                liver
              25-hydroxycholecaliciferol
                                   ↓
                           kidneys
     1,25-dihydroxycholecaliciferol → target tissue
                       Dr. Siham Gritly               92
deficiency results in harmful changes in bone, a condition
  known as rickets in children and osteomalacia in adults.
Vitamin D–Deficiency Symptoms—Bowed Legs and Beaded
                        Ribs of Rickets




                         Dr. Siham Gritly                 93
• Osteoporosis; Any failure to synthesize
  adequate vitamin D or obtain enough from
  foods sets the stage for a loss of calcium from
  the bones, which can result in fractures.
  reduced bone density.




                      Dr. Siham Gritly              94
Dr. Siham Gritly   95
Vitamin E tocopherol
          protect against oxidative damage.

• Vitamin E is an antioxidant a substance that that
  stops chain reactions caused by free radicals that
  can damage cells and affect its normal
  physiological function .
• free radicals: is an unstable and highly reactive
  atoms or molecules that have one or more
  unpaired electrons in the outer orbital
• Vitamin E acts primarily in lipid-rich areas of the
  body, where free radicals can initiate a chain of
  reactions known as peroxidation.

                       Dr. Siham Gritly             96
• peroxidation is a type of reaction in which
  oxygen atoms are formed leading to the
  production of peroxides.
• It is stimulated in the body by certain toxins
  and infections
• Lipid peroxidation reactions break apart fatty
  acids and create free radicals called lipid
  peroxyl radicals (also called reactive oxygen
  species because they contain oxygen radicals).

                     Dr. Siham Gritly          97
• The most concern free radicals in biological
  systems are derived from oxygen, Example of
  free radicals;- Superoxide radical (O2.- ),
  Hydrogen peroxide (H2O2), Hydroxyl radical
  (.OH) and others such as Nitric oxide (.NO)
  and others
• Read more about free radicals


                    Dr. Siham Gritly             98
Dr. Siham Gritly   99
Vitamin K
                  phylloquinone
• The K vitamins exist naturally as;-
•  K1 (phylloquinone) in green vegetables
•  K2 (menaquinone) produced by intestinal bacteria
•  K3 is synthetic menadione.
• Vitamin K can be synthesized by bacteria in the
  intestines.
• Vitamin K is needed for the process of clotting of blood
  and Ca2+ binding.
• Vitamin K is needed for catalyzing the carboxylation of
  the γ-carbon of the glutamate side chain in proteins.

                         Dr. Siham Gritly               100
• Vitamin K’s main function is to help the blood
  clot but it also assists with calcium retention in
  the body.

• Vitamin K contributes to the body’s blood-
  clotting ability by facilitating the conversion of
  precursor proteins, such as prothrombin, to
  active clotting factors thrombin that promote
  blood coagulation.

                       Dr. Siham Gritly           101
• Green leafy vegetables (such as spinach, broccoli
  and cabbage) are rich in vitamin K but eggs and
  milk also contain lower levels of the vitamin.

• Deficiency can be very serious and cause
  heavy, uncontrolled bleeding in multiple areas of
  the body.
• consuming too much vitamin K can damage both
  blood cells and liver.
                      Dr. Siham Gritly            102
Dr. Siham Gritly   103
References

•   Murry K. Robert, Granner K. daryl, Mayes A. peter, Rodwell W. Victor (1999). Harpers Biochemistry. Appleton and
    Lange , twent fifth edition

•   Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts:
    Pearson Prentice Hall

•   A. Burtis, Edward R. Ashwood, Norbert W. Tietz (2000), Tietz fundamentals of clinical chemistry

•   Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David
    LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. pp.
    52–59
•   Maitland, Jr Jones (1998). Organic Chemistry. W W Norton & Co Inc (Np). p. 139. ISBN 0-393-97378-6.

•   Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York: W. H.
    Freeman and Company.



•   Matthews, C. E.; K. E. Van Holde; K. G. Ahern (1999) Biochemistry. 3rd edition. Benjamin Cummings.
•   http://wiki.answers.com/Q/What_is_dehydration_synthesis#ixzz2BuiK645




                                                   Dr. Siham Gritly                                               104
•   D. Voet, J. G. Voet, Biochemistry, second edition ed., John Wiley &
•   Sons, New York, 1995

•   Sareen Gropper, Jack Smith and James Groff, Advanced Nutrition and Human Metabolism, fifth ed.
    WADSWORTH

•   Melvin H Williams 2010; Nutrition for Health, Fitness and Sport. 9th ed, McGraw Hill
•
•   Heymsfield, SB.; Baumgartner N.; Richard and Sheau-Fang P. 1999. Modern Nutrition in Health and Disease;
    Shils E Maurice, Olson A. James, Shike Moshe and Ross A. Catharine eds. 9th edition

•   Guyton, C. Arthur. 1985. Textbook of Medical Physiology. 6th edition, W.B. Company
•   Lehninger. Principles of bochemistry. by Nelson and Cox, 5th Edition; W.H. Freeman and Company

•   Emsley, John (2011). Nature's Building Blocks: An A-Z Guide to the Elements (New ed.). New York, NY: Oxford
    University Press. ISBN 978-0-19-960563-7.

•   Koppenol, W. H. (2002). "Naming of New Elements (IUPAC Recommendations 2002)" (PDF). Pure and Applied
    Chemistry 74 (5): 787–791. doi:10.1351/pac200274050787.
    http://media.iupac.org/publications/pac/2002/pdf/7405x0787.pdf.

•
    http://www.differencebetween.com/difference-between-acyl-and-vs-acetyl/#ixzz2HmrSvksL



                                                    Dr. Siham Gritly                                           105

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Physiological roles of vitamins

  • 1. physiological roles of Vitamins Prepared by; Dr. Siham Gritly Dr. Siham Gritly 1
  • 2. glossary • Vitamin (water soluble vitamin, fat soluble vitamin): an organic substance needed in small amounts for normal body functions that the body cannot synthesize in adequate amounts • enzyme: a protein that is a catalyst • cofactor: a small, inorganic or organic substance that facilitates enzyme action; includes bothorganic coenzymes made from vitamins and inorganic substances such as minerals • Coenzymes are non-protein organic molecules that are mostly derivatives of vitamins soluble in water by phosphorylation; they bind apoenzyme to proteins to produce an active holoenzyme Dr. Siham Gritly 2
  • 3. • prosthetic group: a cofactor permanently associated with the protein, often covalently bound • holoenzyme: catalytically active enzyme-cofactor complex. • apoenzyme: an enzyme without its cofactor enzymatically inactive protein • FADH2 flavin adenine dinucleotide (reduced form); a molecule, central to metabolism, which carries a pair of electrons only slightly less energetic than those of NADH • NADH nicotinamide adenine dinucleotide (reduced form); a molecule, central to metabolism, which carries a pair of high-energy electrons Dr. Siham Gritly 3
  • 4. • free radicals: unstable and highly reactive atoms or molecules that have one or more unpaired electrons in the outer orbital • 1,25-dihydroxyvitamin D: vitamin D that is made from the hydroxylation of calcidiol in the kidneys; the biologically active hormone; also called calcitriol or active vitamin D. • 25-hydroxyvitamin D: vitamin D found in the • blood that is made from the hydroxylation of cholecalciferol in the liver; also called calcidiol • acetyl CoA; a 2-carbon compound (acetate, or acetic acid) to which a molecule of CoA is attached. • antioxidant: a substance that signifi cantly decreases the adverse effects of free radicals on normal physiological functions Dr. Siham Gritly 4
  • 5. Vitamins • Vitamins are organic molecules needed for variety of biological function within the body. • The most important role of the vitamins is to serve as cofactors (co-enzymes) for enzymatic reactions. • protein + coenzyme (vitamin)= enzyme • protein + cofactor (metal ion)= enzyme • the vitamins cannot be synthesized by mammalian cells and, therefore, must be supplied in the diet in small quantities (microgram or milligram per day). Dr. Siham Gritly 5
  • 6. Coenzyme and vitamins • Most of the B vitamins are coenzymes and are essential in facilitating the transfer of atoms or groups of atoms between molecules in the formation of carbohydrates, fats, and proteins • coenzymes: complex organic molecules that work with enzymes to facilitate the enzymes’ activity. Many coenzymes have B vitamins as part of their structures. Dr. Siham Gritly 6
  • 7. • coenzymes is to act as transporters of chemical groups from one reactant to another. • Examples include; • - nicotinamide adenine dinucleotide (NAD), which accepts hydrogen (and gives it up in another reaction), • -ATP, which gives up phosphate groups while transferring chemical energy Dr. Siham Gritly 7
  • 8. The vitamins are of two distinct types, water soluble and fat soluble. Water Soluble Vitamins Fat Soluble Vitamins Thiamin (B1) Vitamin A Riboflavin (B2) Niacin (B3) Vitamin D Pantothenic Acid (B5) Pyridoxal, Pyridoxamine, Vitamin E Pyridoxine (B6) Biotin Vitamin K Cobalamin (B12) Folic Acid Ascorbic Acid Dr. Siham Gritly 8
  • 9. Water soluble vitamins • -soluble in water, consist of carbon, hydrogen, oxygen nitrogen, sulfur, cobalt, • -deficiency usually occur more than fat soluble vitamins • -Water-soluble vitamins that body cannot store Dr. Siham Gritly 9
  • 10. • -enter in energy production and in essential enzyme system. They help with release of energy from carbohydrates, proteins, and fats • -activate chemical reaction inside the body and act as coenzymes • -excretion in urine through urination • -the most important water soluble vitamins are B complex and vitamin C Dr. Siham Gritly 10
  • 11. Thiamine or vitamin B1 • thiamine-sulfur containing water soluble vitamin of B complex, exist in tissues in the active form of Thiamine Pyrophosphate (TPP) • - Thiamine Pyrophosphate (TPP) is essential co-enzyme involve in energy extraction and cellular process in catabolism of sugar and amino acid • -human and other animal obtain it through diet Dr. Siham Gritly 11
  • 12. • The majority of thiamine in serum is bound to proteins, mainly albumin. • Approximately 90% of total thiamine in blood is in erythrocytes (red blood cell). Dr. Siham Gritly 12
  • 13. • Thiamin is rapidly converted to its active form, thiamin pyrophosphate, TPP, in the brain and liver by a specific enzyme;- • thiamin diphosphotransferase. • TPP is necessary as a cofactor for the;- • 1-pyruvate dehydrogenase (PDH) and • 2-α-ketoglutarate dehydrogenase catalyzed reactions associated with the TCA cycle • 3-transketolase catalyzed reactions of the pentose phosphate pathway Dr. Siham Gritly 13
  • 14. Thiamin functions • -the main function of thiamine is its role in metabolic reaction acting as co-enzyme for energy and carbohydrate metabolism • -its deficiency in tissues affect energy metabolism and thus affect nerve and cardiac functions Dr. Siham Gritly 14
  • 15. TPP is necessary as a cofactor for the important enzyme pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase and transketolase • 1-Pyruvate dehydrogenase is the key enzyme in CHO metabolism to complete oxidation (via the TCA cycle) • TPP participate in catalyzing oxidative decarboxylation of pyruvate, to form acetyl- CoA in citric acid cycle, where a carboxyl group is removed from a compound and released as CO2. Dr. Siham Gritly 15
  • 16. An example is the conversion of pyruvate to acetyl- CoA, which is irreversible, during CHO metabolism • Oxidative decarboxylation reactions are oxidation reactions in which a carboxylic group is removed, forming CO2 Dr. Siham Gritly 16
  • 17. • 2-α-ketoglutarate dehydrogenase -thiamine involved in decarboxylation of alph ketoglutrate to succinate in krebs cycle by the emzyme α-ketoglutarate dehydrogenase • -deficiency of thiamine lead to accumulation of pyruvate in the blood thus affect peripheral nervous system and heart Dr. Siham Gritly 17
  • 18. • 3-transketolase; catalyzed reactions of the pentose phosphate pathway • oxidative phase, NADPH is generated when glucose 6-phosphate is oxidized to ribose 5- phosphate. Dr. Siham Gritly 18
  • 19. deficiency of thiamin • -two different diseases may result as deficiency of thiamin • 1-Beri Beri (wet and dry beri beri) Usually beri beri diseases result due to long term deficiency and high intake of carbohydrates • -Korsakoff syndrome (psychosis) Dr. Siham Gritly 19
  • 20. • Wernicke-Korsakoff syndrome; This disease is most commonly found in chronic alcoholics due to their poor dietetic lifestyles. • Wernicke-Korsakoff syndrome is characterized by acute encephalopathy (brain dysfunction) followed by chronic impairment of short-term memory Dr. Siham Gritly 20
  • 21. • - Wet beriberi is associated with mental confusion, muscular atrophy, edema, tachycardia, caridomegaly and congestive heart failure in addition to peripheral neuropathy (is damage to nerves of the peripheral nervous system • - Dry beriberi is characterized principally by peripheral neuropathy. Muscle become waste and week, difficult walking, patient become bedridden and may die. Dr. Siham Gritly 21
  • 22. Beriberi is a disease caused by a deficiency of thiamine (vitamin B1) that affects many systems of the body, including the muscles, heart, nerves, and digestive system Dr. Siham Gritly 22
  • 23. Riboflavin, vitamin B2 • Active form of riboflavin is Riboflavin Phosphate • It is the central component of the cofactor FAD and FMN, and therefore required for energy metabolism • vitamin B2 is required for a wide variety of cellular processes transferring oxygen from plasma to the tissues. • It plays a key role in energy metabolism, and for the metabolism of fats, ketone bodies, carbohydrates and proteins. Dr. Siham Gritly 23
  • 24. • Vitamin B2, or riboflavin is an intermediary the transfer of electrons in the cellular oxidation-reduction reactions which generate energy from protein, carbohydrate and fat FAD and FMN. • The riboflavin coenzymes are also important for the transformation of vitamin B6 and folic acid into their respective active forms, and for the conversion of tryptophan into niacin. Dr. Siham Gritly 24
  • 25. • Synthesis of these two cofactors occurs in a two step process. • 1-FMN is synthesized from riboflavin via the ATP-dependent enzyme riboflavin kinase (RFK). • RFK introduces a phosphate group onto the terminal hydroxyl of riboflavin. Dr. Siham Gritly 25
  • 26. • 2-FMN is then converted to FAD via the attachment of AMP (derived from ATP) though the action of FAD pyrophosphorylase Dr. Siham Gritly 26
  • 27. Deficiency of riboflavin • In humans, signs and symptoms of riboflavin deficiency • -include cracked and red lips, inflammation of the lining of mouth and tongue, mouth ulcers, cracks at the corners of the mouth (Angular cheilitis), and a sore throat. • -A deficiency may also cause dry and scaling skin, fluid in the mucous membranes, and iron- deficiency anemia. The eyes may also become bloodshot, itchy, watery and sensitive to bright light. Dr. Siham Gritly 27
  • 28. Riboflavin Deficiency Riboflavin Deficiency Riboflavin Deficiency (Cheilosis) (Glossitis Dr. Siham Gritly 28
  • 29. Niacin Vitamin B3 nicotinic acid, nicotinamide, niacinamide • Niacin (nicotinic acid and nicotinamide) is also known as vitamin B3. • Both nicotinic acid and nicotinamide can serve as the dietary source of vitamin B3. • Niacin is required for the synthesis of the active forms of vitamin B3, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Dr. Siham Gritly 29
  • 30. • NADH, NAD+, NADP+ and NADPH which are coenzymes found in all living cells. • NAD+ and NADP+ are oxidizing agents.(loss of electron) • NADH and NADPH are reducing agents.(gain of electron) reactions involved dehydrogenase enzymes electron transport and hydrogen carrier involved in fats, carbohydrates and protein metabolism Dr. Siham Gritly 30
  • 31. Niacin functions Role of NAD+ in oxidation-reduction reactions 1-reaction of transport hydrogen atom from one part to another, occur in mitochondria and cytoplasm of the cells –oxidative reactions of NAD------NADH *glycolysis -------glyceraldehyde 3P to 1,3 diphosphglycerate *oxidative decarboxylation of pyruvate to lactate Dr. Siham Gritly 31
  • 32. oxydation of acetyl Co A in TCA cycle -malate to oxaloacetate -glutamate to α ketoglutrate *β oxidation of fatty acid 2-NAD----dehydrogenase for catabolism of vitamin B6 pyridoxal to its excretory product (pyridoxin acid) Dr. Siham Gritly 32
  • 33. 3-NADPH (reduced form) involved in; Fatty acid synthesis Cholesterol synthesis Deoxy-ribonucleotide molecules (DNA) 4-NADPH--- convert folate to dihydrofolate (DHF) and synthesis of 5 methyl- tetrahydrofolate the active form of folic acid Dr. Siham Gritly 33
  • 34. niacin deficiency • Severe deficiency of niacin in the diet causes the disease pellagra characterized by three Ds; Diarrhea, loss of fluids Dermatitis, hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances, Dementia, (mental symptoms) such as irritability, poor concentration, anxiety, fatigue, restlessness, apathy, a nd depression Dr. Siham Gritly 34
  • 35. Pellagra niacin deficiency Dr. Siham Gritly 35
  • 36. Pellagra niacin deficiency Dr. Siham Gritly 36
  • 37. Pyridoxine vitamin B6 • Pyridoxal, • pyridoxamine • Pyridoxine • are collectively known as vitamin B6. • The three forms equal vital activities in their active forms • found in different types of food such as; Wheat germ, Sunflower seeds, Dry Soybeans, Walnuts, Soybean flour Lentils Brown rice peas Bananas, Chicken, white fish, Potatoes Dr. Siham Gritly 37
  • 38. • All three compounds are efficiently converted to the biologically active form of vitamin B6, pyridoxal phosphate (PLP). • -pyridoxal phosphate • -pyridoxine phosphate • -pyridoxamine phosphate • This conversion is catalyzed by the ATP requiring enzyme, pyridoxal kinase. • Pyridoxal kinase requires zinc for full activity thus making it a metaloenzyme. Dr. Siham Gritly 38
  • 39. • Pyridoxal phosphate functions as a cofactor in enzymes involved in transamination reactions required for the synthesis and catabolism of the amino acids • Act as co-enzyme needed in amino acid metabolism such as conversion of essential amino acid tryptophan to vitamin niacin Dr. Siham Gritly 39
  • 40. • Also it function in glycogenolysis as a cofactor for glycogen phosphorylase • Vitamin B6 is involved in over 100 metabolic reactions in the body, including the production of energy and hemoglobin, a protein in red blood cells. Intakes below the DRI can hurt performance. • Deficiencies of vitamin B6 are rare and usually are related to an overall deficiency of all the B-complex vitamins Dr. Siham Gritly 40
  • 41. • Factors which reduce Vitamin B6 absorption • Exposure of Vitamin B6 containing foods to ultraviolet light • Cooking • Exposure to alkaline pH • Food processing destroys up to 90% of Vitamin B6 content in food Dr. Siham Gritly 41
  • 42. • Factors which increase Vitamin B6 excretion • Smoking • Excess alcohol • Excessive tea /coffee caffeinated drinks consumption • Use of hormonal contraception • Use of drugs such as diuretics, • Excessive protein consumption Dr. Siham Gritly 42
  • 43. Pantothenic acid • Pantothenic acid is used in the synthesis of co- enzyme A (CoA). • This coenzyme is formed when the vitamin combines with a derivative of ADP and the amino acid cysteine. • Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. Dr. Siham Gritly 43
  • 44. • CoA is also important in the biosynthesis of many important compounds such as fatty acids, cholesterol. • CoA is important in energy metabolism for pyruvate to enter the Kerbs cycle or tricarboxylic acid cycle (TCA cycle) as acetyl- CoA, • and for α-ketoglutarate to be transformed to succinyl-CoA in the cycle. Dr. Siham Gritly 44
  • 45. Deficiency of Pantothenic Acid • deficiency of pantothenic acid in rats leads to elevated serum concentrations of triglycerides and non-esterified fatty acids, reflecting impaired β- oxidation. • with B-oxidation would have an effect on fat use. Co-A is also necessary in CHO metabolism, as it is a part of acetyl-CoA Dr. Siham Gritly 45
  • 46. Folic acid (pteroylglutamic acid) • The folates are a group of heterocyclic compounds consisting of a pteridine ring structure linked to para- aminobenzoic acid (PABA) that forms pteroic acid. • Pteridine is a group of organic compounds having two fused six-member rings each containing two nitrogen atoms and four carbon atoms. • One of the rings is a pyrimidine, the other a pyrazine. Dr. Siham Gritly 46
  • 47. Folic acid (pteroylglutamic acid) is composed of three large sub- components. 1-pteridine ring,2- para-amino benzoic acid, and 3- glutamic acid. Glutamic acid is an amino acid that the body can actually synthesize by itself and is found in proteins. Folic acid gets its name from the Latin word folium meaning "leaf", since it's found in many leafy plants. Dr. Siham Gritly 47
  • 48. • The number of glutamate molecules affects the absorption and metabolism of folate or folic acid in the body. Dr. Siham Gritly 48
  • 49. active form of folic acid is tetrahydrofolate Chemical structure of THF. The N5 and N10-nitrogen atoms that can carry one-carbon functional groups Dr. Siham Gritly 49
  • 50. Pteroylglutamate (folic acid) Polyglutamate is the storage form of folic acid in the liver • Folic acid is reduced within cells (principally the liver where it is stored) to; tetrahydrofolate (THF also H4folate) through the action of dihydrofolate reductase (DHFR), an NADPH-requiring enzyme. • When stored in the liver or ingested folic acid exists in a polyglutamate form Dr. Siham Gritly 50
  • 51. • Deficiency causes megaloblastic anemia as for vitamin B12 deficiency. • The inability to synthesize DNA during erythrocyte maturation leads to abnormally large erythrocytes termed macrocytic anemia • Folic acid is important in preventing neuraltube defects (NTDs) in the developing human fetus. Dr. Siham Gritly 51
  • 52. megaloblastic macrocytic anemia Dr. Siham Gritly 52
  • 53. Vitamin B12 cyanocobalamin • Vitamin B12 is the name for a class of related compounds that have the vitamin activity. These compounds contain the rare element cobalt. • Humans can not synthesis B12 and must obtain it from diet. Enzymes that catalyze certain rearrangement reaction required B12 or its derivatives. • Vitamin B12 is synthesized exclusively by microorganisms and is found in the liver of animals bound to protein as methycobalamin or 5'-deoxyadenosylcobalamin. Dr. Siham Gritly 53
  • 54. • The vitamin must be hydrolyzed from protein in order to be active. • Hydrolysis occurs in the stomach by gastric acids or the intestines by trypsin following consumption of animal meat. • The vitamin is then bound by intrinsic factor, a protein secreted by parietal cells of the stomach, and carried to the ileum where it is absorbed. • Following absorption the vitamin is transported to the liver in the blood bound to transcobalamin II. Dr. Siham Gritly 54
  • 55. • Vitamin B12 is involved in a number of body processes, but is mainly; • formation to red blood cell production, • nervous system function, • sperm production, • normal growth • the proper function of the immune system. Dr. Siham Gritly 55
  • 56. There are only two clinically significant reactions in the body that require vitamin B12 as a cofactor. • 1- During the catabolism of fatty acids with an odd number of carbon atoms and the amino acids valine, isoleucine and threonine the resultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCA cycle. • One of the enzymes in this pathway, methylmalonyl-CoA mutase, requires vitamin B12 as a cofactor in the conversion of methylmalonyl-CoA to succinyl-CoA. • The 5'-deoxyadenosine derivative of cobalamin is required for this reaction. Dr. Siham Gritly 56
  • 57. • 2-The second reaction requiring vitamin B12 catalyzes the conversion of homocysteine to methionine and is catalyzed by methionine synthase. • This reaction results in the transfer of the methyl group from N5-methyltetrahydrofolate to hydroxycobalamin generating tetrahydrofolate (THF) and methylcobalamin during the process of the conversion Dr. Siham Gritly 57
  • 58. Deficiencies of B12 Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency • The liver can store up to six years vitamin B12, therefore deficiencies in this vitamin are rare. • Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result a lack of intrinsic factor in the stomach leading to malabsorption of the vitamin. Dr. Siham Gritly 58
  • 59. • Pernicious anemia characterized by abnormally large and immature red blood cells. • Other symptoms include muscle weakness and irreversible neurological damage • The anemia results from impaired DNA synthesis due to a block in purines and thymidine biothynthesis. Dr. Siham Gritly 59
  • 60. Biotin • Biotin, one of the water soluble B- vitamins, occurs in 8 different forms but only one of these, D-biotin, is found in nature and has full vitamin activity • It is water soluble and important in the metabolism of fatty acids and the amino acid Leucine Dr. Siham Gritly 60
  • 61. • Biotin in its coenzyme form participates in numerous reactions involved in the metabolism of fat and CHO • involved in carboxylation reactions, e.g. acetyl- CoA carboxylase and pyruvate carboxylase. • participates in the entry of certain carbon skeletons from amino acids into the energy- yielding pathways, as well as in DNA synthesis. Dr. Siham Gritly 61
  • 62. • Biotin is found in numerous foods and also is synthesized by intestinal bacteria and as such deficiencies of the vitamin are rare. • Deficiencies are generally seen only after long antibiotic therapies which deplete the intestinal fauna or following excessive consumption of raw eggs. • The latter is due to the affinity of the egg white protein, avidin, for biotin preventing intestinal absorption of the biotin. Dr. Siham Gritly 62
  • 63. Deficiency is rare, but can result in:Anorexia Nausea Vomiting Dermatitis • Symptoms that may appear if biotin is deficient are extreme exhaustion, drowsiness, muscle pain, loss of appetite, depression, and grayish skin color. • Some of the richest sources of biotin are tomatoes, romaine lettuce, and carrots. Additional sources include onions, cabbage, cucumber, cauliflower, mushroo ms, peanuts, almonds, walnuts, oat meal, bananas, raspberries, strawberries, soy, egg yolk, and cow and goat milk. Dr. Siham Gritly 63
  • 64. Vitamin C Ascorbic Acid Main physiological roles of vitamin C • Vital component of all body cells • Essential for manufacture of collagen, needed for healthy connective tissue, skin, bones and vascular system • Powerful Antioxidant • Stimulates white blood cells and antibody production • Required for proper wound healing and tissue regeneration Dr. Siham Gritly 64
  • 65. • Assists iron absorption • powerful effects on the production of important chemicals for the control of hormones and brain function. • plays a vital role in the immune system • It is a key component of collagen • Vitamin C also helps to benefit the skin, teeth, and bones. Dr. Siham Gritly 65
  • 66. • Deficiency leads to a disease called Scurvy. • Scurvy is a disease that affects the blood vessels, skin, and the body’s healing process, resulting in anemia, hemorrhaging of the skin, and gum disease (gingivitis). • Vitamin C is found in most plants and animals Dr. Siham Gritly 66
  • 67. • People requiring additional Vitamin C. • some specific groups who are likely to benefit more ; • People with heart disease (angina, heart attack, "hardened arteries", coronary artery disease, other vascular disease, high blood pressure) • Diabetics • Those with poorly healing wounds (such as leg ulcers) • People with skin problems Dr. Siham Gritly 67
  • 68. Examples of Coenzymes and Vitamins reference; Cooper GM; The Central Role of Enzymes as BiologicalCatalysts The Cell: A Molecular Approach. 2nd edition Coenzyme Related vitamin Chemical reaction NAD+, NADP+ Niacin Oxidation-reduction FAD Riboflavin (B2) Oxidation-reduction Thiamine Thiamine (B1) Aldehyde group pyrophosphate transfer Coenzyme A Pantothenate Acyl group transfer Tetrahydrofolate Folate Transfer of one- carbon groups Biotin Biotin Carboxylation Pyridoxal Pyridoxal (B6) Transamination phosphate Dr. Siham Gritly 68
  • 69. Fat soluble vitamins • Fat soluble vitamins dissolve within the body’s fat cells and are usually found in fats and fatty foods. • If they are not needed immediately, the body will store fat soluble vitamins for later use in the liver and fatty tissues • fat soluble vitamins do not need to be consumed as frequently as water soluble vitamins to ensure proper functioning of the body’s cells. Dr. Siham Gritly 69
  • 70. Vitamin A • Vitamin A consists of three biologically active molecules, • 1-retinol, (hydroxyl) involved in vision • 2- retinal (aldehyde) involved in vision • 3-retinoic acid. (carboxyl) • Importance for cellular differentiation (regulate gene expression) • Each of these compounds are derived from the plant precursor molecule, β-carotene (a member of a family of molecules known as carotenoids). Dr. Siham Gritly 70
  • 71. • Beta-carotene, which consists of two molecules of retinal linked at their aldehyde ends, is also referred to as the provitamin form of vitamin A. • Vitamin A is found in dark green and yellow vegetables and yellow fruits, such as broccoli, spinach, turnip greens, carrots, squash, sweet potatoes, pumpkin, cantaloupe, and apricots, and in animal sources such as liver, milk, butter, cheese, and whole eggs. Dr. Siham Gritly 71
  • 72. Absorption, transport and storage • Ingested β-carotene is cleaved in the lumen of the intestine by β-carotene dioxygenase to yield retinal. • Retinal is reduced to retinol by retinaldehyde reductase, an NADPH requiring enzyme within the intestines. • Retinol is esterified to palmitic acid and delivered to the blood via chylomicrons. The uptake of chylomicron by the liver results in delivery of retinol to this organ for storage as a lipid ester within lipocytes (adipose tissues). Dr. Siham Gritly 72
  • 73. • Transport of retinol from the liver to extrahepatic tissues occurs by binding of hydrolyzed retinol to aporetinol binding protein (RBP). • the retinol-RBP complex is then transported to the cell surface within the Golgi and secreted. Within extrahepatic tissues retinol is bound to cellular retinol binding protein (CRBP). • Plasma transport of retinoic acid is accomplished by binding to albumin Dr. Siham Gritly 73
  • 74. Vitamin A functioning as vitamin and hormone • retinol and retinoic acid with in the cell bind to specific receptor present in the nucleolus of tissues • This receptor-vitamin complex interact with several genes that involved in growth and cell differentiation thus affect expression of genes • cell differentiation is the process by which immature cells develop specific functions different from those of the original that are characteristic of their mature cell type. Dr. Siham Gritly 74
  • 75. Vision and Vitamin A • the process of vitamin A in vision known as Rhodopsin cycle or Ward’s visual cycle the • Photoreception in the eye is the function of two specialized cell types located in the retina; • Rods • Cones • Both rod and cone cells located in the retina contain a photoreceptor pigment in their membranes and vitamin A is a component of these pigments Dr. Siham Gritly 75
  • 76. • the rod;- The opsin of rod cells is called Rhodopsin (visual purple) consist of 11-cis retinal bound to protein opsin (vision in dim light) • Rhodopsin absorbs light, 11-cis retinal is converted to all trans retinal • The isomerization act on the conformation change in the protein opsin • This process lead to generate nerve impulse that transmitted to brain through the optic nerve Dr. Siham Gritly 76
  • 77. • This is followed by dissociation of the trans retinal from opsin • The trans retinal is immediately isomerised by the enzyme isomerase to 11-cis retinal • 11-cis retinal combines with opsin to regenerate rhodopsin and complete the vision cycle Dr. Siham Gritly 77
  • 78. • cone cells, contain colour pigments, *porphyropsin (red) • *Iodopsin (green) • *Cyanopsin (blue) • The pigments are converted to trans retinal and the protein opsin is released • The reaction stimulate the nerve impulse thus the brain red the colour Dr. Siham Gritly 78
  • 80. Vitamin A Deficiency • Vitamin A is stored in the liver and deficiency of the vitamin occurs only after prolonged lack of dietary intake. • The earliest symptoms of vitamin A deficiency are night blindness. • Additional early symptoms include follicular hyperkeratinosis, increased susceptibility to infection and cancer and anemia equivalent to iron deficient anemia. • Prolonged lack of vitamin A leads to deterioration of the eye tissue through progressive keratinization of the cornea, a condition known as xerophthalmia. Dr. Siham Gritly 80
  • 81. The earliest symptoms of vitamin A deficiency ;- *impaired dark adaptation –night blindness (nyctalopia) *poor vision in dim light *xerophthalmia The first stage of xerophthalmia is conjunctival xerosis Later Bitot’s spots form (keratinization of epithelial cells) A deficiency progresses degenerative changes of retina occurs (keratomalcia) Dr. Siham Gritly 81
  • 82. keratomalcia Softening and drying and ulceration of the cornea resulting from vitamin A deficiency developed in the cornea that lead to blindness Dr. Siham Gritly 82
  • 83. Xerophthalmia Xerophthalmia is a severe drying of the eye surface caused by a malfunction of the tear glands. it occurs most commonly because of decreased intake or absorption of vitamin A. Symptoms include night blindness and eye irritationthe eyes being very dry, there is a loss of luster on their surface . Ulceration and necrosis developed in the cornea that lead to blindness Dr. Siham Gritly 83
  • 84. Vitamin D cholecalciferol • Vitamin D is known as the sunshine vitamin because exposure to sunlight prompt the body’s cells to start producing it. • Vitamin D2 functions as a steroid hormone and vitamin • regulate calcium and phosphorous homeostasis • dairy products (such as eggs, milk and butter), fatty fish and fish oils are all good sources of vitamin D. Dr. Siham Gritly 84
  • 85. Vitamin D comes in many forms, but the two most important in the diet arel • 1-plant sterol ergosterol which isolated from plant and by commercial irradiation light UV converted to vitamin D2 or ergocalciferol not found in human tissues • 2-animal sources or naturally produced called vitamin D3 or cholecalciferol. Dr. Siham Gritly 85
  • 86. Formation of vitamin D3 in the skin • The naturally found vitamin D3 cholecalciferol is the form obtained either from animal sources or made in the skin by the action of ultraviolet light from the sun on 7-dehydrocholesterol • 7-dehydrocholesterol found in animal tissues synthesized in the sebaceous glands of the skin and secreted into the skin surface • During exposure to sunlight 7-dehydrocholesterol forming pre-cholecalcefirol (previtamin D3) Dr. Siham Gritly 86
  • 87. activation of vitamin D must be achieved through; • 1-Liver • 2-kidneys • In the Liver;- cholecalciferol fuses into the blood carried by D-binding protein (DBP) known as transcalciferin to the liver • By the action of liver enzyme 25-hydroxylase hydroxylate cholecaciferol at carbon 25 to form 25- OH cholecalciferol/D3 • The activity of this enzyme related to the concentration of vitamin D • 25-hydroxylase also found in lungs, intestine and Dr. Siham Gritly 87 kidneys
  • 88. • In the kidneys;-a second hydroxylation of 25-OH D3 (25-hydroxylcalcefirol) occur at position 1 • by the action of enzyme;- • 1-hydroxylase, 25-cholecalsiferol hydrolyized to 1,25-(OH)2 cholecalecalciferol or known as (calcitriol ) the active form of vitamin D • By the transporter DBP which is the major protein in the blood transported the active form calcitriol (1,25-(OH)2 cholecalciferol) to the target tissues Dr. Siham Gritly 88
  • 89. • Active form of the hormone The biologically active form of the hormone is; 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also called 1,25-dihydroxycholecalciferol or calcitriol). Dr. Siham Gritly 89
  • 90. • The activity of 1-hydroxylase is influenced by • -parathyroid hormone • -low plasma concentration • -The concentration of 1,25 hydoxycholecaciferol- high concentration inhibit the enzyme activity,- low concentration stimulate it • Low intake of phosphours Dr. Siham Gritly 90
  • 91. • 25-(OH)D3 can also be hydroxylated at the 24 position by a specific D3-24-hydroxylase in the kidneys, intestine, placenta and cartilage Dr. Siham Gritly 91
  • 92. 1,25-dihydroxcholecaliciferol D3 formation Tissue cholesterol ↓ Sun ↓ 7-dehydrocholesterol Plasma Cholecaliciferol D3 ↓ liver 25-hydroxycholecaliciferol ↓ kidneys 1,25-dihydroxycholecaliciferol → target tissue Dr. Siham Gritly 92
  • 93. deficiency results in harmful changes in bone, a condition known as rickets in children and osteomalacia in adults. Vitamin D–Deficiency Symptoms—Bowed Legs and Beaded Ribs of Rickets Dr. Siham Gritly 93
  • 94. • Osteoporosis; Any failure to synthesize adequate vitamin D or obtain enough from foods sets the stage for a loss of calcium from the bones, which can result in fractures. reduced bone density. Dr. Siham Gritly 94
  • 96. Vitamin E tocopherol protect against oxidative damage. • Vitamin E is an antioxidant a substance that that stops chain reactions caused by free radicals that can damage cells and affect its normal physiological function . • free radicals: is an unstable and highly reactive atoms or molecules that have one or more unpaired electrons in the outer orbital • Vitamin E acts primarily in lipid-rich areas of the body, where free radicals can initiate a chain of reactions known as peroxidation. Dr. Siham Gritly 96
  • 97. • peroxidation is a type of reaction in which oxygen atoms are formed leading to the production of peroxides. • It is stimulated in the body by certain toxins and infections • Lipid peroxidation reactions break apart fatty acids and create free radicals called lipid peroxyl radicals (also called reactive oxygen species because they contain oxygen radicals). Dr. Siham Gritly 97
  • 98. • The most concern free radicals in biological systems are derived from oxygen, Example of free radicals;- Superoxide radical (O2.- ), Hydrogen peroxide (H2O2), Hydroxyl radical (.OH) and others such as Nitric oxide (.NO) and others • Read more about free radicals Dr. Siham Gritly 98
  • 100. Vitamin K phylloquinone • The K vitamins exist naturally as;- • K1 (phylloquinone) in green vegetables • K2 (menaquinone) produced by intestinal bacteria • K3 is synthetic menadione. • Vitamin K can be synthesized by bacteria in the intestines. • Vitamin K is needed for the process of clotting of blood and Ca2+ binding. • Vitamin K is needed for catalyzing the carboxylation of the γ-carbon of the glutamate side chain in proteins. Dr. Siham Gritly 100
  • 101. • Vitamin K’s main function is to help the blood clot but it also assists with calcium retention in the body. • Vitamin K contributes to the body’s blood- clotting ability by facilitating the conversion of precursor proteins, such as prothrombin, to active clotting factors thrombin that promote blood coagulation. Dr. Siham Gritly 101
  • 102. • Green leafy vegetables (such as spinach, broccoli and cabbage) are rich in vitamin K but eggs and milk also contain lower levels of the vitamin. • Deficiency can be very serious and cause heavy, uncontrolled bleeding in multiple areas of the body. • consuming too much vitamin K can damage both blood cells and liver. Dr. Siham Gritly 102
  • 104. References • Murry K. Robert, Granner K. daryl, Mayes A. peter, Rodwell W. Victor (1999). Harpers Biochemistry. Appleton and Lange , twent fifth edition • Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts: Pearson Prentice Hall • A. Burtis, Edward R. Ashwood, Norbert W. Tietz (2000), Tietz fundamentals of clinical chemistry • Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. pp. 52–59 • Maitland, Jr Jones (1998). Organic Chemistry. W W Norton & Co Inc (Np). p. 139. ISBN 0-393-97378-6. • Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York: W. H. Freeman and Company. • Matthews, C. E.; K. E. Van Holde; K. G. Ahern (1999) Biochemistry. 3rd edition. Benjamin Cummings. • http://wiki.answers.com/Q/What_is_dehydration_synthesis#ixzz2BuiK645 Dr. Siham Gritly 104
  • 105. D. Voet, J. G. Voet, Biochemistry, second edition ed., John Wiley & • Sons, New York, 1995 • Sareen Gropper, Jack Smith and James Groff, Advanced Nutrition and Human Metabolism, fifth ed. WADSWORTH • Melvin H Williams 2010; Nutrition for Health, Fitness and Sport. 9th ed, McGraw Hill • • Heymsfield, SB.; Baumgartner N.; Richard and Sheau-Fang P. 1999. Modern Nutrition in Health and Disease; Shils E Maurice, Olson A. James, Shike Moshe and Ross A. Catharine eds. 9th edition • Guyton, C. Arthur. 1985. Textbook of Medical Physiology. 6th edition, W.B. Company • Lehninger. Principles of bochemistry. by Nelson and Cox, 5th Edition; W.H. Freeman and Company • Emsley, John (2011). Nature's Building Blocks: An A-Z Guide to the Elements (New ed.). New York, NY: Oxford University Press. ISBN 978-0-19-960563-7. • Koppenol, W. H. (2002). "Naming of New Elements (IUPAC Recommendations 2002)" (PDF). Pure and Applied Chemistry 74 (5): 787–791. doi:10.1351/pac200274050787. http://media.iupac.org/publications/pac/2002/pdf/7405x0787.pdf. • http://www.differencebetween.com/difference-between-acyl-and-vs-acetyl/#ixzz2HmrSvksL Dr. Siham Gritly 105