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
