This document discusses protein metabolism and the metabolism of amino acids. It notes that proteins are the most abundant organic compounds in the body, making up 10-12kg of dry weight, and perform many structural and functional roles. Amino acids are the building blocks of proteins and there are 20 naturally occurring amino acids, with 10 being non-essential and needing to be synthesized by the body. The amino acid pool is maintained through intake from dietary proteins and synthesis of non-essential amino acids, and is utilized for protein synthesis and other metabolic processes. Protein metabolism involves the constant breakdown and resynthesis of body proteins.

1. M.Prasad Naidu
MSc Medical Biochemistry, Ph.D,.

2.  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.  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.  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.  1. Turnover of body protein
 2. intake of dietary protein
 3. synthesis of non- EAAs

6.  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.  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.  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.  10 out of 20 naturally occurring AAs can be
synthesized by the body which contributes to AA
pool.

10.  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.  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.  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.  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.  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.  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

16.  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.  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.

18.  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.  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

20.  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.

21.  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

22.  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

23.  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.

24.  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