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Lipid & Protein Metabolism




                 Submitted To: Raja Tahir
                 Submitted By:
                 Waqas Nawaz       (11-Arid-975)
                 Mujahid Hussain (11-Arid-981)
Lipids are basically the fats in the body which include cholesterol, triglycerides and phospholipids. The main

components of these are fatty acids which are released when the lipids are broken down.


Lipids are metabolized through following steps:


    1) Absorption

    2) Lipolysis

    3) β-Oxidation

    4) Ketgoenesis or Ketone Bodies

    5) Lipogenesis

1. Absorption

Fatty acids are absorbed through the intestine and are taken up via the lymphatic system.Fats can be utilised for

energy or may be stored as adipose tissue




Lipolysis:
           Complete hydorlysis of triglyceride yeild gelycerol and 3 fatty acids

                 Fatty acids are activated before being catabolized (oxidized).

                 Activated fatty acids are then transported from cytosol to the mitochondrial matrix with the help of

                  carnitine transporter.




          CH3
                                                      O                                   CH3
              +                    O
H3C       N       CH2 CH CH2 C                                                                +                  O
                                           +
          CH3          OH
                                 O
                                               CoAS   C     R                      H3C    N       CH2 CH CH2 C
                                                                                                                 O   +   CoASH
                                                                                          CH3
                                                 acyl CoA                                            O
          carnitine

                                                                                                     C    O

                                                                                                     R

                                                                                         acyl carnitine

                 Now it can get transported across inner mitochondrial membrane whre it is oxidized

β-Oxidation:
                 Breakdown of fats into
                      Acetyl coenzyme A  Krebs Cycle
                      FADH2  Oxidative Phosphorylation
                      NADH  Oxidative Phosphorylation
                 Breaks off two carbons at a time to acetyl CoA
                      Remaining goes another round
Reactions of Beta Oxidation:

       In Reaction 1,Oxidation

                    Removes H atoms from α & β carbons of Acyl CoA
                    Forms a trans C=C bond
                    Reduces FAD to FADH2




                                                              FAD             FADH2
                                   O
                                                                                                                                O

R     CHReaction 2,HydrationC
      In 2 CH2      CH2                    S-CoA                                         R         CH       CH        CH2        C        S-CoA
                                                             Acyl-CoA Dehydrogenase
            Adds water across the trans C=C bond
      acyl-CoA                                                                                                beta-enoyl CoA
            Forms a hydroxyl group (-OH) on the β-carbon
            Forms β-hydroxy product
                                                                    H2O
                                    O                                                                        OH                  O


R     CH         CH         CH2     C       S-CoA                                              R     CH2     CH          CH2     C        S-CoA
                                                                enoy l-CoA hy dratase
    beta-enoyl CoA                                                                                      beta-hydroxyacyl CoA




       In Reaction 3,Second Oxidation

                    Oxidizes the hydroxyl group
                    Forms a keto group on β-carbon
                    Produces NADH
             OH                   O                        NAD+            NADH                                                   O
                                                                                                             O

R     CH2    CH            CH2    C       S-CoA                                                R     CH2     C           CH2      C       S-CoA
                                                         beta-hydroxyacyl-CoA
                                                             dehydrogena se                                      beta-ketoacyl CoA
        beta-hydroxyacyl CoA



       In Reaction 4,Acetyl CoA is cleaved

                    By splitting the bond between α & β carbon
                    To form a shortend fatty acyl CoA that repeats steps 1-4 of β-oxidation
                                                                                                        O
                                                                                                                               acetyl CoA
                                   O                                                           CH3      C        S-CoA
                 O
                                                                  HSCoA
R      CH2       C          CH2    C      S-CoA                                                                                       O

                 beta-ketoacyl CoA
                                                                                                                 R        CH2         C     S-CoA
                                                                          thiola se
                                                                                                                         acyl CoA
Overview Of β-Oxidation Reactions:




Per β-Oxidation cycle:

    1 FADH2…………………………1.5 ATP
    1 NADH………………………….2.5 ATP
    1 Acetyl CoA to Krebs
              3 NADH X 2.5 ATP / NADH………7.5 ATP
              1 FADH2…………………………….1.5 ATP
              1 GTP………………………………..1.0 ATP

-----------------------------------------------------------------------

                       Total = 14.0 ATP




Cycles Of β-Oxidation:

         Determines the number of oxidations & the total number of Acetyl CoA groups
Ketogenesis or Ketone Bodies:
Ketogenesis occurs when there is a high rate of fatty acid oxidation in the Liver

In ketogenesis

        Body fat breaks down to meet energy needs
        Keto compounds called ketone bodies form
        Starvation causes accumulation of acetyl CoA
        Not enough carbohydrates to keep Kreb’s Cycle going
        Acetyl CoA forms acetoacetate, β-hydroxybutyrate & acetone
        Ketone bodies are formed in uncontrolled diabetes mellitus & starvation
Comparison of Fat Metabolism per gram and CHO per gram
    Fats provide about 9 kilocalories per gram and carbohydrates provide about 4 kilocalories per gram.

    Using nutritional units, that is 9 Calories/gram for fats and 4 Calories/gram for carbohydrates.

    CHO provide energy more quickly

    Fats are good fuel for endurance events, but not sprint

                      Overview / Summary Of Lipid Metabolism
1)  Lipids are digested and absorbed with the help of bile salts
2)  Products of lipid digestion aggregate to form mixed micelles and are absorbed into the small intestine
3)  Lipids are transported in the form of lipoproteins
4)  Fatty acids are activated, transported across mitochondrial membrane with the help of carnitine transporter
5)  β -oxidation of saturated fatty acids takes place in the mitochondrial matrix. Similarly oxidation of
    unsaturated and odd chain fatty acids also take place with additional reactions
6) Ketone bodies are formed in the liver but they are utilized by extra hepatic tissues. In uncontrolled diabetes
    mellitus and starvation, excessive ketone bodies are formed, leading to ketosis
  7) Fatty acid biosynthesis takes place in the cytosol of cells. Fat gets deposited in the adipose tissue. Acetyl
               Coenzyme A is the precursor of fatty acid synthesis as well as cholesterol biosynthesis.
The body consists of a large variety of proteins with various structures and functions. The main
component of proteins is amino acids. Approximately 20 different amino acids make up the
building blocks of all proteins. Amino acids are classified as essential (meaning they are required
in the diet as the body can't synthesise them) and non-essential (meaning the body can generate
them if needed).

The correct balance of amino acids is needed so that all important proteins can be synthesized.
When proteins are digested, the bonds between amino acids are broken and they are released.
Normally the amino acids will be recycled and used to produce new proteins. However if energy
sources are limited, the amino acids may be used to generate energy.

Protein metabolism occurs in following steps:
   1) Transamination
   2) Oxidative Deamination

Transamination:
      Mechanism for conversion of non-essential amino acids into keto acids

      Enzymes are aminotransferases or transaminases

      Transfer of amino group from one amino acid into keto acid
Oxidative Deamination:
       Removes the amino group as an ammonium ion from glutamate
       Provides α-ketoglutarate for transamination




       General Reaction Is:




               Ammonia is converted to urea and excreted through urea cycle
Fate Of The Carbon Skeleton:

Carbon skeletons are used for energy

Glucogenic: TCA cycle intermediates or pyruvate (gluconeogensis)

Ketogenic: Acetyl CoA, Acetoacetyl CoA, or Acetoacetate
Overview Of Protein Metabolism
   Proteins are hydrolyzed to form peptides
   Peptides are converted to amino acids by hydrolysis
   Amino acids are converted into ammonia & keto acid
   Ammonia is excreted through body by urea cycle




           Summary: Lipid and Protein Metabolic Reactions
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Lipid & protein metabolism

  • 1. Lipid & Protein Metabolism Submitted To: Raja Tahir Submitted By: Waqas Nawaz (11-Arid-975) Mujahid Hussain (11-Arid-981)
  • 2. Lipids are basically the fats in the body which include cholesterol, triglycerides and phospholipids. The main components of these are fatty acids which are released when the lipids are broken down. Lipids are metabolized through following steps: 1) Absorption 2) Lipolysis 3) β-Oxidation 4) Ketgoenesis or Ketone Bodies 5) Lipogenesis 1. Absorption Fatty acids are absorbed through the intestine and are taken up via the lymphatic system.Fats can be utilised for energy or may be stored as adipose tissue Lipolysis:
  • 3. Complete hydorlysis of triglyceride yeild gelycerol and 3 fatty acids  Fatty acids are activated before being catabolized (oxidized).  Activated fatty acids are then transported from cytosol to the mitochondrial matrix with the help of carnitine transporter. CH3 O CH3 + O H3C N CH2 CH CH2 C + O + CH3 OH O CoAS C R H3C N CH2 CH CH2 C O + CoASH CH3 acyl CoA O carnitine C O R acyl carnitine  Now it can get transported across inner mitochondrial membrane whre it is oxidized β-Oxidation:  Breakdown of fats into Acetyl coenzyme A  Krebs Cycle FADH2  Oxidative Phosphorylation NADH  Oxidative Phosphorylation  Breaks off two carbons at a time to acetyl CoA Remaining goes another round
  • 4. Reactions of Beta Oxidation: In Reaction 1,Oxidation  Removes H atoms from α & β carbons of Acyl CoA  Forms a trans C=C bond  Reduces FAD to FADH2 FAD FADH2 O O R CHReaction 2,HydrationC In 2 CH2 CH2 S-CoA R CH CH CH2 C S-CoA Acyl-CoA Dehydrogenase  Adds water across the trans C=C bond acyl-CoA beta-enoyl CoA  Forms a hydroxyl group (-OH) on the β-carbon  Forms β-hydroxy product H2O O OH O R CH CH CH2 C S-CoA R CH2 CH CH2 C S-CoA enoy l-CoA hy dratase beta-enoyl CoA beta-hydroxyacyl CoA In Reaction 3,Second Oxidation  Oxidizes the hydroxyl group  Forms a keto group on β-carbon  Produces NADH OH O NAD+ NADH O O R CH2 CH CH2 C S-CoA R CH2 C CH2 C S-CoA beta-hydroxyacyl-CoA dehydrogena se beta-ketoacyl CoA beta-hydroxyacyl CoA In Reaction 4,Acetyl CoA is cleaved  By splitting the bond between α & β carbon  To form a shortend fatty acyl CoA that repeats steps 1-4 of β-oxidation O acetyl CoA O CH3 C S-CoA O HSCoA R CH2 C CH2 C S-CoA O beta-ketoacyl CoA R CH2 C S-CoA thiola se acyl CoA
  • 5. Overview Of β-Oxidation Reactions: Per β-Oxidation cycle:  1 FADH2…………………………1.5 ATP  1 NADH………………………….2.5 ATP  1 Acetyl CoA to Krebs 3 NADH X 2.5 ATP / NADH………7.5 ATP 1 FADH2…………………………….1.5 ATP 1 GTP………………………………..1.0 ATP ----------------------------------------------------------------------- Total = 14.0 ATP Cycles Of β-Oxidation:  Determines the number of oxidations & the total number of Acetyl CoA groups
  • 6. Ketogenesis or Ketone Bodies: Ketogenesis occurs when there is a high rate of fatty acid oxidation in the Liver In ketogenesis  Body fat breaks down to meet energy needs  Keto compounds called ketone bodies form  Starvation causes accumulation of acetyl CoA  Not enough carbohydrates to keep Kreb’s Cycle going  Acetyl CoA forms acetoacetate, β-hydroxybutyrate & acetone  Ketone bodies are formed in uncontrolled diabetes mellitus & starvation
  • 7. Comparison of Fat Metabolism per gram and CHO per gram  Fats provide about 9 kilocalories per gram and carbohydrates provide about 4 kilocalories per gram.  Using nutritional units, that is 9 Calories/gram for fats and 4 Calories/gram for carbohydrates.  CHO provide energy more quickly  Fats are good fuel for endurance events, but not sprint Overview / Summary Of Lipid Metabolism 1) Lipids are digested and absorbed with the help of bile salts 2) Products of lipid digestion aggregate to form mixed micelles and are absorbed into the small intestine 3) Lipids are transported in the form of lipoproteins 4) Fatty acids are activated, transported across mitochondrial membrane with the help of carnitine transporter 5) β -oxidation of saturated fatty acids takes place in the mitochondrial matrix. Similarly oxidation of unsaturated and odd chain fatty acids also take place with additional reactions 6) Ketone bodies are formed in the liver but they are utilized by extra hepatic tissues. In uncontrolled diabetes mellitus and starvation, excessive ketone bodies are formed, leading to ketosis 7) Fatty acid biosynthesis takes place in the cytosol of cells. Fat gets deposited in the adipose tissue. Acetyl Coenzyme A is the precursor of fatty acid synthesis as well as cholesterol biosynthesis.
  • 8.
  • 9. The body consists of a large variety of proteins with various structures and functions. The main component of proteins is amino acids. Approximately 20 different amino acids make up the building blocks of all proteins. Amino acids are classified as essential (meaning they are required in the diet as the body can't synthesise them) and non-essential (meaning the body can generate them if needed). The correct balance of amino acids is needed so that all important proteins can be synthesized. When proteins are digested, the bonds between amino acids are broken and they are released. Normally the amino acids will be recycled and used to produce new proteins. However if energy sources are limited, the amino acids may be used to generate energy. Protein metabolism occurs in following steps: 1) Transamination 2) Oxidative Deamination Transamination:  Mechanism for conversion of non-essential amino acids into keto acids  Enzymes are aminotransferases or transaminases  Transfer of amino group from one amino acid into keto acid
  • 10. Oxidative Deamination:  Removes the amino group as an ammonium ion from glutamate  Provides α-ketoglutarate for transamination  General Reaction Is:  Ammonia is converted to urea and excreted through urea cycle
  • 11. Fate Of The Carbon Skeleton: Carbon skeletons are used for energy Glucogenic: TCA cycle intermediates or pyruvate (gluconeogensis) Ketogenic: Acetyl CoA, Acetoacetyl CoA, or Acetoacetate
  • 12. Overview Of Protein Metabolism  Proteins are hydrolyzed to form peptides  Peptides are converted to amino acids by hydrolysis  Amino acids are converted into ammonia & keto acid  Ammonia is excreted through body by urea cycle Summary: Lipid and Protein Metabolic Reactions
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