Amino acid metabolism - PowerPoint PPT Presentation

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Amino acid metabolism

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Title: Amino acid metabolism


1
Metabolism of Amino Acids
  • M.Prasad Naidu
  • MSc Medical Biochemistry, Ph.D,.

2
introduction
  • Proteins ? most abundant org.compound
  • Major part of the body dry wt (10-12Kg)
  • Perform wide variety of functions. Viz
  • 1. Static functions ( Structural functions)
  • 2. Dynamic functions( Enzy, hor, receptors)
  • Half of the body protein is (Collagen) is present
    in supportive tissue (skeletan connective)
    while the other half is intracellur.

3
introduction
  • Proteins are the N- containing macro molecules
  • Consists of L- AAs as repeating units
  • Of the 20 AAs half can be synthesized
  • Essential and non-essential AAs
  • Proteins on degradation release AAs
  • Each AA undergoes its own metabolism
  • Proteins metabolism is more appropriately learnt
    as metabolism of amino acids.

4
Amino Acid Pool
  • An adult has about 100 gm of Free AA which
    represent the AA pool of the body.
  • Glutamate and Glutamine together constitute about
    50 and EAA 10 of the body pool.
  • The conc of intracellular AA is always higher
    than the Extracellular AA
  • AAs enter the cells againt Active transport
  • The AA pool is maintained by the sources that
    contribute ( input) and the metabolic pathways
    that utilize (out put) the amino acids.

5
Sources of AA Pool
  • 1. Turnover of body protein
  • 2. intake of dietary protein
  • 3. synthesis of non- EAAs

6
Protein turnover
  • The protein present in the body is in a dynamic
    state.
  • About 300-400 gm of protein per day is constantly
    degraded and synthesized which represent the body
    protein turnover.
  • There is wide variation the turnover of
    individual proteins.
  • Eg plasma proteins digestive enzymes are
    rapidly degraded ( half life is hrs/days)
  • Structural proteins have long half lives often
    months and years.

7
Control of protein turnover
  • many factors
  • 1. Ubiquitin small PP 8,500 tags with the
    proteins and facilitates degradation.
  • 2. PEST Sequences - Certain proteins with Pro,
    Gln, Ser, Thr sequence are rapidly degraded.

8
Dietary Protein
  • Regular loss of protein due to degradation of
    AAs.
  • About 30-50 gm protein is lost every day from the
    body.
  • This amount must be supplied daily in the diet to
    maintain N Balance.
  • There is no storage form of AAs unlike the
    Carbohydrates and lipids (TG)
  • The excess AAs metabolised oxidized Energy
    or glucose or fat.
  • The daily protein intake by adults is 40-100gm

9
Synthesis of AAs
  • 10 out of 20 naturally occurring AAs can be
    synthesized by the body which contributes to AA
    pool.

10
Utilization of AAs from body pool
  • 1. most of the body proteins (300-400g/D)
    degraded are synthesized from the AA pool. (
    enzymes, hormones, immuno proteins, contractile
    proteins)
  • Many imp N compounds ( porphyrins, purines
    pyrimidines) are produced from AA . About 30g of
    protein is daily utilized for this purpose.
  • Generally, about 10-15 of body energy
    requirements are met from the AAs
  • The AAs are converted to Car, fats. This becomes
    predominant when the protein consumption is in
    excess of the body requirements.

11
Metabolism of amino acidsgeneral aspects
  • AAs undergo common reactions
  • Transamination followed by
  • Deamination for the liberation of NH3
  • The NH2 group of AAs is utilized for the
    formation of urea (excretory end product of
    protein metabolism)
  • The C-skeleton of the AAs is first converted to
    keto acids (by transamination) which meet one or
    more of the following fates

12
Fate of keto acids
  • Utilized to generate energy
  • Used for the synthesis of glucose
  • Derived for the formation of fat / ketone bodies
  • Involved in the production of non-EAAs

13
Transamination
  • Transfer of an amino group from an AA to a keto
    acid
  • This process involves the interconversion of a
    pair of AAs and a pair of keto acids
  • Transaminases / aminotransferases

14
Salient features of Transamination
  • All transaminases require PALP
  • Specific transaminases exist for each pair of
    amino and keto acids
  • However, only two namely Asp. transaminase Ala.
    transaminase make a significant contribution for
    transamination
  • There is no free NH3 liberated, only the transfer
    of NH3 group occurs
  • Reversible
  • Production of non-EAAs as per the requirement of
    the cell
  • Diverts the excess of AAs towards Energy
    generation

15
Salient features of Transamination
  • AAs undergo TAN to finally concentrate N in
    glutamate
  • Glutamate is the only AA that undergoes OD to
    liberate free NH3 for urea synthesis
  • All AAs except Lys, Thr, Pro Hy.pro participate
    in TAN
  • TAN is not restricted to a-group only. (eg
    d-amino group of Ornithine is transaminated.
  • Serum transaminases are important for diagnostic
    and prognostic purposes
  • SGPT or ALT is elevated in all liver diseases
  • SGOT or AST is increased in myocardial infarction

16
Mechanism of Transamination
  • Occurs in 2 stages.
  • 1. Transfer of the NH2 group to the coenzyme PLP
    ( bound to the coenzyme) to form Pyridoxamine
    Phosphate.
  • 2. The NH2 group of Pyridoxamine PO4 is then
    transferred to a keto acid to produce a new AA
    and the enzyme with PLP is regenerated.

17
Mechanism of Transamination
  • All the transaminases require PLP , a derivative
    of Vit B6
  • The CHO group of PLP is linked with ?-NH2 group
    of Lys, at the active site of the enzyme forming
    a Schiffs base (imine linkage)
  • When an AA comes in contact with the enzyme, it
    displaces lys and a new Schiff base linkage is
    formed.
  • The AA-PLP-Schiff base tightly binds with the
    enzyme by non covalent forces.
  • Snell Braustein proposed Ping-Pong Bi Bi
    mechanism involving a series of intermediates (
    aldimines ketimines) in transamination reaction.

18
Deamination
  • The removal of amino group from the AAs as NH3
  • Transamination involves only shuffling of NH3
    groups among the AAs
  • Deamination results in the liberation of NH3 for
    urea synthesis
  • Simultaneously, the C-skeleton of AAs is
    converted to keto acids
  • 2 types (Oxidative Non oxidative)
  • Transamination Deamination occurs
    simultaneously, often involving glutamate as the
    central molecule (Transdeamination)

19
Oxidative deamination
  • Liberation of free NH3 from the AAs coupled with
    oxidation
  • Liver kidney
  • Purpose of OD to provide NH3 for urea synthesis
    a-ketoacids for a variety of reactions,
    including Energy generation

20
Role of GDH
  • In the process of Transamination, the NH3 groups
    of most of the AAs are transferred to a-KG to
    produce glutamate
  • Thus , glutamate serves as a collection centre
    for amino groups in the biological system
  • Glutamate rapidly undergoes oxi.deamination by
    GDH to liberate NH3
  • GDH is unique in that it can use utilize either
    NAD or NADP
  • Conversion of glutamate to a-KG occurs through
    the formation of a-iminoglutarate
  • GDH catalyzed reaction is imp as it reversibly
    links up glutamate metabolism with TCA cycle
    through a-KG
  • GDH is involved in both catabolic anabolic
    reactions.

21
Regulation of GDH activity
  • Zn containing mitochondrial enzyme
  • Complex enzyme containing 6 identical units with
    a mol.wt of 56000 each.
  • GDH is controlled by allosteric regulation
  • GTP , ATP, steroid Thyroid hormones are
    inhibitors of GDH
  • GDP and ADP are activators
  • After ingestion of protein meal, liver glutamate
    level is ?.
  • It is converted to a-KG with liberation of NH3
  • Further , when cellular E levels are ?low, the
    degradation of glutamate is ? to provide a-KG
    which enters TCA cycle to liberate Energy

22
Oxidative deamination by AAoxidases
  • L- AAoxidase D-AAoxidase are flavo proteins,
    possessing FMN and FAD respectively.
  • They act on corresponding AAs to produce
    a-Ketoacids NH3
  • In this reaction, O2 is reduced to H2O2, which is
    later decomposed by catalase
  • The activity of L-AAoxidase is much low while
    D-AAoxidase is high in tissues (liver kidneys)
  • L-AAoxidase does nt act on Gly
    dicarboxylicacids

23
Fate of D-aminoacids
  • D-AAs are found in plants mos
  • Absent in mammalian proteins
  • But D-AAs are regularly taken in diet and are
    metabolized
  • D-AAoxidase converts them into a-ketoacids by od.
  • The a-ketoacids so produced undergo TAN to be
    converted to L-AAs
  • Ketoacids may be oxidized to generate energy or
    serve as precursor for glucose fat synthesis
  • Thus D-AAoxidase is imp as it initiates the first
    step for the conversion of unnatural D-AAs to
    L-AAs in the body.

24
Non oxidative deamination
  • Some of the AAs can be deaminated to liberate NH3
    without undergoing oxidation
  • A) Aminoacid dehydrases
  • Ser,Thr,Homoserine? a-ketoacids
  • Catalyzed by PLP dependent dehydrases
    (dehydratases)
  • B)Aminoacid desulfhydrases
  • Cys, homocysteine ? pyruvate
  • Deamination coupled with desulfhydration
  • C) Deamination of histidine
  • Histidine ? urocanate
  • histidase
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