hvt

1. Protein Metabolism
transamination
Deamination
urea cycle
Miss Hira Zahid

2.  Proteins are the most abundant organic
compounds & constitute a major part of the
body dry weight (10-12kg in adults).
 Perform a wide variety of structural & dynamic
(enzymes, hormones, clotting factors,
receptors) functions.
 Proteins are nitrogen containing
macromolecules consisting of amino acids as
the repeating units.

4.  Of the 20amino acids found in proteins, half
can be synthesized by the body (non-
essential) & half are supplied through diet
(essential).
 The proteins on degradation release
individual amino acids.
 Each amino acid undergoes its own
metabolism & performs specific functions.

5.  Some amino acids serve as precursors for
the synthesis of many biologically important
compounds.
 Certain amino acids may directly act as
neurotransmitters (e.g glycine, aspartate,
glutamate)

6.  Transamination
 Oxidative Deamination
 Ammonia Transport
 Urea Cycle

7.  The transfer of an amino (-NH2) group from an
amino acid to a ketoacid, with the formation
of a new amino acid & a new keto acid.
 Catalysed by a group of enzymes
called transaminases
(aminotransferases)
 Pyridoxalphosphate (PLP)– Co-factor.
 Liver, Kidney, Heart, Brain - adequate amount
of these enzymes.

9.  All transaminases require PLP
.
 No free NH3 liberated, only the transfer of
amino group.
 Transamination is reversible.
 There are multiple transaminase enzymes
which vary in substrate specificity.
 AST& ALT make a significant contribution for
transamination.

10.  Transamination is important for
redistribution of amino groups & production
of non-essential amino acids.
 It diverts excess amino acids towards the
energy generation.
 Amino acids undergo transamination to
finally concentrate nitrogen in glutamate.

11.  Glutamate undergoes oxidative
deamination to liberate free NH3 for urea
synthesis.
 All amino acids except, lysine, threonine,
proline & hydroxyproline participate in
transamination.
 It involves both anabolism & catabolism,
since – reversible.

12. AA1 + α- KG ketoacid1 + Glutamate
Alanine + α- KG
Aspartate + α-
KG
Pyruvate + Glutamate
Oxaloacetetae +Glutamate

15.  Step:1
 Transfer of amino group from AA1 to the
coenzyme PLP to form pyridoxamine
phosphate.
 Amino acid1 is converted to Keto acid2.
 Step:2
 Amino group of pyridoxamine phosphate is
then transferred to a keto acid1 to produce a
new AA 2 & enzyme with PLP is

16.  Enzymes, present within cell, released in
cellular damage into blood.
 ↑ AST - Myocardial Infarction (MI).
 ↑ AST, ALT – Hepatitis, alcoholic cirrhosis.
 Muscular Dystrophy.

17.  The removal of amino group from the amino
acids as NH3 is deamination.
 Deamination results in the liberation of
ammonia for urea synthesis.
 Deamination may be either oxidative or
non-oxidative

18.  Only liver mitochondria contain glutamate
dehydrogenase (GDH) which deaminates
glutamate to α-ketoglutarate & ammonia.
 It needs NAD+ as co-enzyme.
 It is an allosteric enzyme.
 It is activated by ADP & inhibited by GTP.

19.  Oxidative deamination is the liberation of
free ammonia from the amino group of
amino acids coupled with oxidation.
 Site: Mostly in liver & kidney.
 Oxidative deamination is to provide NH3
for urea synthesis & α-keto acids for a
variety of reactions, including energy
generation.

20.  Glutamate is a 'collection centre' for amino
groups.
 Glutamate rapidly undergoes oxidative
deamination.
 Catalysed by GDH to liberate ammonia.
 It can utilize either NAD+ or NADP+.
 This conversion occurs through the
formation of an α-iminoglutarate

22.  The cycle is known as Krebs–Henseleit urea
cycle.
 Ornithine is the first member of the reaction,
it is also called as Ornithine cycle.
 Urea is synthesized in liver & transported to
kidneys for excretion in urine.

23.  The two nitrogen atoms of urea are
derived from two different sources, one
from ammonia & the other directly from
the a- amino group of aspartic acid.
 Urea is the end product of protein metabolism
(amino acid metabolism).

24.  Urea accounts for 80-90%of the nitrogen
containing substances excreted in urine.
 Urea synthesis is a five-step cyclic
process, with five distinct enzymes.
 The first two enzymes are present in
mitochondria while the rest are localized in
cytosol.

25. O

26.  Carbamoyl phosphate synthase I (CPS I) of
mitochondria catalyses the condensation of
NH4
+ ions with CO2to form carbamoyl
phosphate.
 This step consumes two ATP & is
irreversible.
 It is a rate-limiting.

27. CO2+ NH3 + 2 ATP Carbamoyl Phosphate
+ 2ADP + Pi
Carbamoyl phosphate
synthetase-I

28.  The second reaction is also
mitochondrial.
 Citrulline is synthesized from carbamoyl
phosphate & ornithine by ornithine
transcarbamoylase.
 Ornithine is regenerated & used in urea
cycle.

29.  Ornithine & citrulline are basic amino acids.
(Never found in protein structure due to lack
of codons).
 Citrulline is transported to cytosol by a
transporter system.
 Citrulline is neither present in tissue proteins
nor in blood; but it is present in milk.

30. Ornithine + Carbamoyl phosphate Citrulline +
Pi
Ornithine
Transcarbomylas
e

31.  Citrulline condenses with aspartate to form
arginosuccinate by the enzyme
Arginosuccinate synthetase.
 Second amino group of urea is
incorporated.
 It requires ATP
, it is cleaved to AMP & PPi
 2High energy bonds are required.
 Immediately broken down to inorganic
phosphate (Pi).

32.  The enzyme Argininosuccinase or
argininosuccinate lyase cleaves
arginosuccinate to arginine & fumarate (an
intermediate in TCA cycle)
 Fumarate provides connecting link with TCA
cycle or gluconeogenesis.

33. 
 Aspartate is regenerated in this
reaction.
Fumarate Malate
Fumarase MDH
Oxaloacetate Aspartate
Aminotransferase
NAD+ NADH+H+

34.  Arginase is the 5thand final enzyme that
cleaves arginine to yield urea &
ornithine.
 Ornithine is regenerated, enters
mitochondria for its reuse in the urea
cycle.
 Arginase is activated by Co2+& Mn2+
 Ornithine & lysine compete with arginine

35.  Arginase is mostly found in the liver, while the
rest of the enzymes (four) of urea cycle are
also present in other tissues.
 Arginine synthesis may occur to varying
degrees in many tissues.
 But only the liver can ultimately
produce urea.

36.  Toxic ammonia is converted into non-toxic urea.
 Synthesis of semi-essential amino acid-arginine.
 Ornithine is precursor of Proline, Polyamines.
 Polyamines include putrescine, spermidine,
spermine.
 Polyamines have diverse roles in cell growth &
proliferation.

37.  Urea produced in the liver freely diffuses & is
transported in blood to kidneys & excreted.
 A small amount of urea enters the intestine
where it is broken down to CO2 & NH3 by
the bacterial enzyme urease.