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Metabolism
By
Shahzad Bashir
RN, BScN
(NMC ION)
Objectives
Metabolism
By the end of this presentation, you will be able
to:
Define metabolism, catabolism and anabolism. The sum total of the chemical processes that
Define ATP and its relationship with catabolism occur in living organisms, resulting in growth,
and anabolism. production of energy, elimination of waste
material, etc.
Discuss gluconeogenesis,glycogenesis,
glucogenolysis,transamination, deamination and
ketosis. Anabolism- build up of complex molecules
Discuss the following metabolic pathways for Catabolism- break down of complex
carbohydrate, proteins and fats in terms of molecules
glycolysis, kreb’s cycle and electron transport
chain.
Adenosine triphosphate
• An important carrier of energy in cells in the
body and a compound that is important in the
synthesis (the making) of RNA. Adenosine
triphosphate (ATP) is a nucleotide (a building
block of a nucleic acid such as RNA). The body
produces ATP from food and then ATP
produces energy as needed by the body.
•
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Oxidation-Reduction Reactions
Reduction
Oxidation is the removal of electron from an
atom or molecule, the result is decreases in Reduction is the opposite of oxidation,it is the
potential energy of atom or molecule. addition of electrons to a molecule.
Most of biological oxidation reactions involve Example: conversion of pyruvic acid into lactic
the loss of hydrogen atoms, they are called acid.
dehydrogenation reaction. Oxidation and reduction reactions are always
Example conversion of lactic acid into pyruvic coupled ;each time one substance and another is
acid. simultaneously reduced.such paired reactions are
called oxidation-reduction or redox reactions.
Mechanisms of ATP Formation Carbohydrate Metabolism
Substrate-level phosphorylation Primarily glucose
Substrate transfers a phosphate group directly Fructose and galactose enter the pathways at various
Requires enzymes points
Phosphocreatine + ADP Creatine + ATP All cells can utilize glucose for energy production
Oxidative phosphorylation Glucose uptake from blood to cells usually mediated
by insulin and transporters
Method by which most ATP formed
Liver is central site for carbohydrate metabolism
Small carbon chains transfer hydrogens to
transporter (NAD or FADH) which enters the Glucose uptake independent of insulin
electron transport chain The only exporter of glucose
Blood Glucose Homeostasis Fates of Glucose
Several cell types prefer glucose as energy Fed state
source Storage as glycogen
80-100 mg/dl is normal range of blood glucose in Liver
non-ruminant animals Skeletal muscle
Uses of glucose: Storage as lipids
Energy source for cells Adipose tissue
Muscle glycogen Fasted state
Fat synthesis if in excess of Metabolized for energy
needs New glucose synthesized
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High Blood Glucose
Glucose Metabolism
Pancreas
Four major metabolic pathways:
Muscle
Insulin Glycogen Immediate source of energy
Pentophosphate pathway
Glucose absorbed Glucose absorbed Glycogen synthesis in liver/muscle
Adipose Precursor for triacylglycerol synthesis
Cells Energy status (ATP) of
body regulates which
Glucose absorbed pathway gets energy
Same in ruminants and
non-ruminants
Fate of Absorbed Glucose Glucose storage: Glycogenesis
If glucose is not needed immediately for ATP
1st Priority: glycogen storage production, it combines with many other molecules
Stored in muscle and liver of glucose to form glycogen, a polysaccrides that is
the only stored form the CHO in our bodies.
2nd Priority: provide energy
The harmone insuline stimulates the hepatocytes
Oxidized to ATP and skeletal muscle cells to carry out glycogenesis,
3rd Priority: stored as fat the synthesis of glycogen.
Only excess glucose The body can store about 500g(about 1.1 lb) of
glycogen, roughly 75% in skeletal muscle fibres and
Stored as triglycerides in adipose the rest in liver cells.
The body can store about 500 g(1.1 lb)of glycogen.
Contd. Glucose release: Glycogenolysis
During the glycogenesis, glucose is first When body activities require ATP, glycogen
phosphorylated to glucose 6- phosphate by stored in hepatocytes is broken down into
hexokinase. glucose and released into the blood to be
Glucose 6-phosphate is converted to glucose transported to cells, where it will be
1-phosphate, then to uridine diphosphate catabolized by the processes of cellular
glucose and finally to glycogen. respiration.
The process of splitting glycogen to glucose
subunits is called glycogenolysis.
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During digestion, proteins are broken down into
amino acids.
Unlike CHO and TGL, which are stored.
Proteins are not warehoused for future use.
Protein Metabolism Instead, amino acids are either oxidized to
produce ATP or used to synthesized new
proteins for body repair and growth.
Excess dietary amino acids are not excreted in
the urine and feces but instead are converted
into glucose (gluconeogenesis) or TGL
(lipogenesis).
The fate of proteins
Amino acid pool
The active transport of amino acids into body cells is
stimulated by insulinlike growth factors(IGFs) and No storage facility for amino acids
insulin. Amino acids incorporated into functional proteins
Almost immediately after digestion, amino acids are Amino acids in blood and extracellular fluid represent
reassembled into proteins.
an ‘amino acid pool’
Many proteins function as enzymes; others are
involved in transportation(hemoglobin) or serve as Amino acids move through this pool
antibodies, clotting chemicals(fibrinogen), harmones Average 60 kg woman
(insulin) or contractile elementsin muscle fibers(actin 10 kg protein
170 g free amino acids in pool
or myosin).
Fate of amino acids Amino acid metabolism
Protein content of adult body remains
Metabolism of amino acids differs, but 3 common
remarkably constant.
Protein constitutes 10-15% of diet.
10- reactions:
Equivalent amount of amino acids must be lost
each day. Transamination
Proteins synthesis in all body cells and is
Deamination
stimulated by insulin,thyroid harmones and
insulinlike growth factors Formation of urea
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Transamination reactions Deamination reactions
Amino group removed from one amino acid and Amino group (and H) removed
transferred to another Forms ammonia (NH3)
Catalysed by aminotransferase enzymes Carbon skeleton left can be
Nearly all transaminations transfer amino group to α- Oxidised
ketoglutarate used for gluconeogenesis
Forms new ketoacid and glutamate (amino acid) converted to fatty acid
18 amino acids glucogenic/ketogenic
Leucine and lysine purely ketogenic
Urea cycle
Ammonia is toxic
Readily ionises to ammonium ion NH4+
Lipid Metabolism
NH4+ converted to urea in liver (urea cycle)
Urea contains 2 x NH2
One from NH4+
One from aspartate
Urea excreted in urine
Lipid Metabolism
Fats are not water soluble Chylomicron Carriers
Made into bile salts that are
Absorbed as micelles in small intestines. Proteins that carry fats
The lipid and protein combination is lipoproteins stored in adipose tissue
There are four major classes of lipoproteins: It forms in mucosal epithelial cells of the small
intestine, transport dietry (ingested)
Chylomicrons
lipids to adipose tissue for storage.
Very low density lipoproteins(VLDLs) They contain about 1-2% proteins,85%TGL,7%
Low density lipoproteinsI(LDL) phospholipids and 6-7% cholesterol.
High density lipoproteins(HDL)
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Very low density
Low density lipoproteinsI(LDL)
lipoproteins(VLDLs)
Contains 25% proteins, 5% TGL, 20%
Which form in hepatocytes, contain mainly phospholipids and 50% cholesterol.
endogenous lipids (made in the body).
They carry about 75% of the total cholesterol in
VLDLs contain about 10% proteins, 50% TGL, 20 blood and deliver it to cells throughout the body for
% phospholipids and 20% cholesterol. use in repair of cell membranes and synthesis of
steroid harmones and bile salts.
High density lipoproteins(HDL) Lipid catabolism: Lipolysis
Which contain 40-45% proteins,5-10% In order for muscle, liver and adipose tissue to
triglycerides ,30% phospholipids ,and 20% oxidize the fatty acids derived from triglycerides to
cholesterol, remove excess cholesterol from body produce ATP, the triglycerides must first be split into
cells and the blood and transport it to the liver for glycerol and fatty acids, a process called lipolysis.
elimination.Because HDLs prevent accumulation of Lipolysis is catalyzed by enzyme called lipases.
cholesterol in the blood,a high HDL level is Epinephrine and norepinephrine enhance TGL
associated with decreased risk of coronary artery breakdown into fatty acids and glycerol.
disease.for this reason,HDL-cholesterol is known as
“good cholesterol”
As a part of normal fatty acid catabolism, Lipid Anabolism: Lipogenesis
hepatocytes can take two acetyl molecules at a
time and condense them to form acetoacetic acid. Liver cells and adipose cells can synthesize lipids
from glucose or amino acids through lipogenesis,
This reaction liberates the bulky CoA portion, which is stimulated by insulin.
which cannot diffuse out of cells
some acetoacetic acid is converted into beta-
Lipogenesis occurs when individuals consume
hydroxybutyric acid and acetone.
more calories than are needed to satisfy their ATP
The formation of these three substances
needs.
collectively known as ketone bodies, is called
ketogenesis.
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COUPLING OF CATABOLISM AND
ANABOLISM BY ATP Cont.
The chemical reactions of living systems depend when the terminal phosphate group is split off
on the effecient transfer of manageable amounts ATP,adenosine diphosphate [ADP] and a
of energy from one molecule to another. phosphate group[symbolized as (P) are
The molecule that most often performs this task formed .
is ATP. some of the energy released is used to drive
A typical cell cell has about a billion molecules of anabolic reactions such as the formation of
ATP. glycogen from glucose.
Molecule of ATP consists of an adenine molecule
,a ribose molecule,and three phosphate groups
bonded to one another.
Energy Transfer kreb’s cycle
Oxidation is the removal of electrons from a The Krebs cycle named after the person who
substance.
discovered it in 1937, Hans Krebs is known by
Reduction is the addition of electrons to substance.
several other names including:
Two coenzymes that carry hydrogen atoms during
coupled oxidation-reductions are nicotinamide The citric acid cycle
adenine dinucleotide (NAD) and flavin adenine Tricarboxylaic acid cycle(TCA)
dinucleotide (NAD).
ATP can generated via substrate-level
phosphorylation, oxidative phosphorylation and
photophosphorylation.
Contd. Contd.
The purpose of Krebs cycle is to link the In order to apply these concepts to the Krebs
aerobic and anaerobic phases of metabolism cycle, one must understand redox reactions
in order to maximize ATP resynthesis. and the process of ATP resynthesis.
This is accomplished through the oxidation of
high energy organic compounds in the
mitochondrial matrix.
Since free electrons are unable to exist, the
electrons released in an oxidation must be
transferred to a carrier molecule.
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Understanding of redox reactions
Within a cell oxidation and reduction
reactions are always coupled.
In other words, when one substance oxidized
another is simultaneously reduced.
Such coupled reactions are referred to as
redox reactions.
The eight reactions of the Krebs
cycle
1)Entry of the acetyl group.the chemical bond 2)Isomerization.citric acid undergoes
that attaches the acetyl group to coenzyme isomerization to isocitric acid, which has the
a(coA)breaks,and the two- carbon acetyl same molecular formula as
group attaches to a four –carbon molecule of citrate.notice,however, that the hydroxel
oxaloacetic acid to form a six-carbonmolecule group (_oh)is attached to a different carbon.
called citric acid.
CoA is free to combine with another acetyl
group from pyruvic acid and repeat the
process.
3)Oxidative decarboxylation.isocitric acid is 4)Oxidative decarboxylation.alpha-
oxidized and loses a molecule of co2, forming ketoglutaric acid is oxidized ,loses a molecule
alpha-ketoglutaric acid.the h- from the of co2,and picks up coA to form succinyl coa.
oxidation is passed on to nad+,which is
reduced to Nadh+h+.
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5)Substrate-level phosphorylation.coa is 6)Dehydrogenation.succinic acid is oxidized to
displaced by a phosphate group,which is then fumaric acid as two of its hydrogen atoms are
transferred to guanosine diphosphate (gdp) to transferred to the coenzyme flavin adenine
form guanosine triphosphate (gtp).gtp can dinucleutide (fad),which is reduced to fadh2.
donate a phosphate group to adp to form ATP.
7)Hydration.fumaric acid is converted to malic 8)Dehydrogenation.in the final step in the
acid by the addition of a molecule of water. cycle,malic acid is oxidized to re-form
oxaloacetic acid.two hydrogen atoms are
removed are removed and one is transferred
to nad+,which is reduced to nadh+h+.the
regenerated oxaloacetic acid can combine
with another molecule of acetyl coa,beginning
a new cycle.
References
• Tortora 2006.Principles of Anatomy and
Physiology.
• Rose and Wilson,Anatimy and Physiology.
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