Protein turnover, Amino acid pool, Protein metabolism

1. Protein Metabolism
Dr. Ifat Ara Begum
Associate Professor
Dept of Biochemistry
Dhaka Medical College, Dhaka

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6. Protein Turnover
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 Protein turnover is the rate at which body proteins are
constantly being degraded and again resynthesized.
 It is 150-300 gm/day in adult
i.e.
1-2% of total body protein in adult.
[Total body protein in 70kg adult male is 12-14 kg]

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Catabolized portion
(20%) must be
replaced by dietary
protein to maintain
normal body protein
content & nitrogen
balance

9. Nitrogen Balance

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 Nitrogen balance is the difference between nitrogen
intake & nitrogen loss in an individual.
 Three types:
i) Nitrogen Equilibrium: In normal adults
ii) Positive Nitrogen Balance : During growth,
pregnancy
iii) Negative Nitrogen Balance : DM, malignancy, TB,
Trauma, Surgery etc
If loss exceeds 30% of total protein: Fatal

12. Amino Acid Pool

13. What is Amino Acid Pool?
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 It is the free amino acid content distributed throughout
the extracellular fluid
 Quantitatively, it is about 100 gm in an adult individual.
 50% : Glutamate & Glutamine
 10% : Essential Amino Acids
 40% : Other Amino Acids

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15. Intermediary
metabolism of
Amino acid

16. What is Amino Acid?
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Amino group containing carboxylic acid

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Anabolism Catabolism
 Synthesis of:
 NEAA
 Protein
NPN subs
Urea from NH3 via urea cycle
 Glucose, glycogen
 FA, fat, steroid, ketone bodies
 Transamination
 Deamination & removal of NH2 group
as NH3
 Catabolism of amino acid carbon -
skeleton to :
- Pyruvate
- Acetyl CoA
- Intermediates of TCA cycle
 Oxidation of Catabolic end products of
amino acid carbon skeleton via TCA
cycle

19. Transamination

20. Site of transamination :
Cytoplasm of:
 Liver
 Kidney
 Heart
 Sk. Muscle
 Brain.
Rate limiting enzyme:
Aminotransferase
Coenzyme needed:
Pyridoxal phosphate which acts as
an intermediate carrier of an NH2
group.
Nature: Amphibolic & reversible
Substrate: One amino acid & one
keto acid
Product: One keto acid & one amino
acid
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21. What is Transamination?
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 It is the transfer of NH2 group from an amino acid to a
keto acid with simultaneous production of corresponding
keto acid & amino acid respectively.
Remember,
No free NH3 is produced here
Only transfer of NH2 group occurs

22. Amino acid participating
in transamination :
All Amino acids except:
 Lys (Lysine)
 Thr (Threonine)
 Pro (Proline)
Keto acid participating in
transamination:
Three keto acids mostly
participates:
 α- ketoglutarate (ketoacid
of glutamate)
Oxaloacetate (keto acid of
aspartate)
 Pyruvate (ketoacid of
alanine)

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24. Example of Aminotransferase / Transaminase
Alanine transaminase
Aspartate transaminase
Glutamate transaminase.
Clinical importance of these enzymes:
Role as hepatic marker / cardiac marker

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26. Provides a link b/w
carbohydrate, protein &
fat metabolism
Biosynthesis of
NEAA
Importance of
Transamination
Funneling of NH2 group of different
amino acids ultimately to α-KG. α-KG
will form Glutamate
(The major amino acid that undergoes
oxidative deamination)
Formation of C
skeleton / keto acid of
an amino acid:
which can be
catabolized & oxidized to
generate energy

27. Oxidative deamination

28. Site of oxidative deamination:
Mitochondria of:
 Liver
 Kidney
 Heart
 Sk. Muscle
Rate limiting enzyme: Glutamate
dehydrogenase
Coenzyme needed:
NAD.
Nature: Catabolic
Substrate: Glutamate
Product: NH3 & α-KG
Types: Oxidative & Nonoxidative
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29. What is Oxidative Deamination?
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 Removal of –NH2 group from an amino acid in the form of
free NH3 with simultaneous formation of its corresponding
keto acid (C-skeleton)
 Amino acid unique in the process of deamination: Glutamate
Because,
it is the only amino acid that undergoes rapid oxidative
deamination catalyzed by glutamate dehydrogenase
(an active dehydrogenase)

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32. Channel nitrogen of AA
as ammonia to urea cycle
Generate C-
skeleton of AA for
catabolic purpose
Importance of
Deamination

33. Metabolism of ammonia

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35. Sources of
Ammonia
Bacterial degradation of urea into NH3
(by bacterial urease in intestinal lumen)
Catabolism of amino acids
( via Transamination &
deamination)
Catabolism of purine &
pyrimidine nitrogenous
bases
Catabolism of Glutamine
(& Glutamate)

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Glutamine :
The temporary non-toxic storage & transport form
of NH3.

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38. Disposal /
Metabolic fates
of Ammonia
Excretion of NH3 with urine as NH4+ salt
Formation of urea in urea
cycle & its excretion in
urine
Formation of Glutamate & Glutamine
in liver, kidney, muscle, brain

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40. Toxicity which results
from hyperammonemia
(Normal level : 5-
50μmol/L
Brain tissue is mostly
affected & there is
depression in cerebral
activity
Ammonia
Intoxication
Causes of hyperammonemia:
 Hepatic dysfunction (Cirrhosis of liver, hepatic failure)
 Deficiency of enzyme of the urea cycle

41. Biochemical basis of ammonia intoxication / Hepatic
encephalopathy
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 When excessive amounts of ammonia enter the central
nervous system, the brain's defences are severely challenged

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45. Urea cycle

46. Site of Urea cycle :
Mitochondria & cytoplasm of liver
Rate limiting enzyme:
Carbamoylphosphate synthase I
Nature: Anabolic
Substrate: NH3
(Two NH3 participates , one directly
and another from aspartate)
Product: Urea (NH2 – CO – NH2)
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50. Interaction with TCA
cycle
Disposal of NH3
& CO2
Functions /
Importance of urea
cycle
Conversion of toxic
ammonia into nontoxic
urea
Synthesis of NEAA:
 Arginine
 Proline From ornithine

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53. Inborn error of protein metabolism
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 Alkaptonuria
 Homocystinuria
 Phenylketonuria
 Albinism
 Maple syrup urine disease

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