Amino Acids metabolism
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Amino Acids metabolism

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    Amino Acids metabolism Amino Acids metabolism Presentation Transcript

    • M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.
    •  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.
    •  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.
    •  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.
    •  1. Turnover of body protein  2. intake of dietary protein  3. synthesis of non- EAAs
    •  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.
    •  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.
    •  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
    •  10 out of 20 naturally occurring AAs can be synthesized by the body which contributes to AA 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.
    •  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
    •  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
    •  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
    •  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
    •  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 α-group only. (eg: δ-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
    •  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.
    •  All the transaminases require PLP , a derivative of Vit B6  The – CHO group of PLP is linked with έ-NH2 group of Lys, at the active site of the enzyme forming a Schiff’s 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.
    •  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)
    •  Liberation of free NH3 from the AAs coupled with oxidation  Liver & kidney  Purpose of OD: to provide NH3 for urea synthesis & α-ketoacids for a variety of reactions, including Energy generation
    •  In the process of Transamination, the NH3 groups of most of the AAs are transferred to α-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 α-KG occurs through the formation of α- iminoglutarate  GDH catalyzed reaction is imp as it reversibly links up glutamate metabolism with TCA cycle through α-KG  GDH is involved in both catabolic & anabolic reactions.
    •  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 α-KG with liberation of NH3  Further , when cellular E levels are ↓low, the degradation of glutamate is ↑ to provide α-KG which enters TCA cycle to liberate Energy
    •  L- AAoxidase & D-AAoxidase are flavo proteins, possessing FMN and FAD respectively.  They act on corresponding AAs to produce α-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 n’t act on Gly & dicarboxylicacids
    •  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 α-ketoacids by od.  The α-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.
    •  Some of the AAs can be deaminated to liberate NH3 without undergoing oxidation  A) Aminoacid dehydrases:  Ser,Thr,Homoserine α-ketoacids  Catalyzed by PLP dependent dehydrases (dehydratases)  B)Aminoacid desulfhydrases:  Cys, homocysteine  pyruvate  Deamination coupled with desulfhydration  C) Deamination of histidine:  Histidine  urocanate  histidase