The document provides a comprehensive overview of protein metabolism and the associated biochemical processes, highlighting the significance of amino acids and their pool in the body. It explains transamination and deamination, detailing the roles of enzymes, coenzymes, and the urea cycle, which is crucial for detoxifying ammonia by converting it to urea. Additionally, it outlines the steps involved in the urea cycle, emphasizing its energy requirements and the fate of urea in the body.

1. MEGHA T P
MSc FOOD AND NUTRITION
NUTRITIONAL BIOCHEMISTRY

2. INTRODUCTION
 Proteins are the most abundant organic compounds and
constitute major part of the body dry weight(10-12kg in
adults).
 Proteins are nitrogen containing macromolecules consisting
of L-αamino acids as the repeating units.
 Of the 20 amino acids found in the proteins, half can be
synthesized by the body(non-essential) while the rest have to
be provided in the diet(non-essential).
 The proteins on degradation(proteolysis) release individual
amino acids.
 Protein metabolism is more appropriately learnt as
metabolism of Amino acid.

3. AMINO ACID POOL
 The amount of free amino acids distributed throught
the body is called Amino acid pool.
 An adult has about 100g of free amino acids, which
represent the amino acid pool of the body.
 The concentration of intracellular amino acid is always
higher than extracellular amino acid.
 Amino acid pool of the body is maintained by the
sources that contribute(input) and the metabolic
pathways that utilize(output) the amino acids.

5. METABOLISM OF AMINO ACID
 The amino acids undergo certain common reactions like
transamination followed by deamination for the liberation
of ammonia.
 The amino group of amino acids utilized for the formation
of urea, which is the end product of protein metabolism.

7. TRANSAMINATION
 Transfer of amino(-NH2) group from an amino acid to keto
acid is known as transamination.
 This process involves interconversion of a pair of amino acids
and a pair of keto acids, catalysed by a group of enzymes
called transaminases(recently aminotransferases).
 All transaminases require pyridoxal phosphate(PLP), a
coenzyme derived from vitamin B6.
 Transamination is reversible.
 Transamination is important for the redistribution of amino
groups and production of non-essential amino acids, as per the
requirements of the cells.
 Transamination diverts excess amino acids towards energy
generation.

9. MECHANISM OF TRANSAMINATION
.
 Occurs in 2 stages
1. Transfer of amino group to the coenzyme pyridoxal
phosphate to form pyridoxamine phosphate.
2. Amino group of pyridoxamine phosphate is then
transferred to a keto acid to produce new amino acid and
the enzyme with PLP generated

10. Involvement of pyridoxal phosphate in transfer of amino group

11. DEAMINATION
 The removal of amino group from the amino acids as NH3.
 Deamination results in the liberation of ammonia for urea
synthesis.
 Deamination may be either oxidative or non-oxidative.

12. Oxidative deamination Non oxidative deamination
A form of deamination, which generates α-
keto acids and other oxidised products from
amine-containing compounds.
A form of deamination, which liberate ammonia
without undergoing oxidation.
Only occurs in the liver and kidney. Occurs in other type of organisms
Enzyme: Glutamate dehydrogenase (GDH). Main form of enzymes: Amino acid dehydratases
Primary type of amino acid: Glutamic acid
Hydroxy amino acids including serine,
homoserine, and threonine.
Coenzymes are responsible for the oxidation
reaction.
Non oxidising agents

13. UREA CYCLE
 Urea is the end product of protein metabolism.
 The nitrogen in amino acid, converted to ammonia, is toxic
to the body. It is converted to urea and detoxified.
 Urea is synthesized in liver and transported to kidney for
excretion.
 Urea cycle is the first metabolic cycle that was elucidated by
Hans krebs and Kurt henseleit (1932), hence it is known as
Krebs-Henseleit cycle.
 Urea has 2 amino (-NH2) groups, one derived from NH3
and the other from aspartate.
 Carbon atom is supplied by CO2.

14.  Urea synthesis is a 5 step cyclic process, with 5 distinct enzymes.
 First 2 enzymes are present in mitochondria and others are
located in cytosol.
STEPS OF UREA CYCLE
1. SYNTHESIS OF CARBAMOYL PHOSPHATE
 Carbomoyl phosphate synthase1(CPS1) of mitochondria
catalyses the condensation of NH4
+ ions with CO2 to form
carbamoyl phosphate.
 This step consumes 2ATP and is irreversible.
 CPS1 requires N-acetyl glutamate for its activity.

15. 2. FORMATION OF CITRULLINE
 Citrulline is synthesized from carbamoyl phosphate and
ornithine by Ornithine transcarbamoylase.
 Ornithine is generated and used in urea cycle.
 Ornithine and citrulline are basic amino acids. They never
found in protein structure due to lack of codons.
 Citrulline produced in this reaction is transported to cytosol
by transporter system.
3. SYNTHESIS OF ARGINOSUCCINATE
 Arginosuccinate synthase condenses citrulline with aspartate
to produce arginosuccinate.
 This step requires ATP which is cleaved to AMP and
Pyrophosphate(PPI).

16.  Later it’s immediately broken down into inorganic
phosphate(Pi).
4.CLEAVAGE OF ARGINOSUCCINATE
 Arginosuccinase cleaves arginosuccinate to give arginine and
fumarate.
 Arginine is the immediate precursor of urea.
5.FORMATION OF UREA
 Arginine is the fifth and final enzyme that cleaves arginine to
yield urea and ornithine.
 Ornithine so generated enters mitochondria for its use in
the urea cycle.

18. OVERALL REACTIONS AND ENERGETICS.
 Urea cycle is irreversible and cunsumes 4 ATP
 2 ATPs utilised for synthesis of carbamoyl phosphate.
 1 ATP converted to AMP & PPI to produce arginosuccinate
which equal to 2ATP.
NH4+ CO2+Aspartate+3ATP urea+fumarate+2ATP+2Pi+AMP+Ppi
DISPOSAL OF UREA
 Urea produced in the liver freely diffuses and is
transported in blood to kidneys and excreted.
 Small amount of urea enters the intestine where it is
broken down to CO2 and NH3 by bacterial enzyme urease.

19.  The ammonia is either lost in the faeces or absorbed into the
blood.