brief overview of metabolism of all the essential & non essential amino acids along with their metabolic defects and special proteins synthesized from them

1. PROTEIN
METABOLISM
PRESENTED BY
DR KRITIKA AGARWAL
BDS

2. Topic Overview
 Introduction
 Amino acid pool
 Overview of amino acid metabolism
 Metabolism of ammonia
 Metabolism of individual amino acids
 One carbon metabolism

3. Introduction
 Metabolism of proteins is the metabolism of amino acids
 Metabolism of amino acids is a part of the nitrogen metabolism
in body
 Nitrogen enters the body in the form of dietary protein
 Dietary proteins cant be stored as such but used for formation
of tissue proteins
 For the formation of a new tissue protein all the essential amino
acids that cant be synthesized by the body(provided by dietary
protein) must be present at the same time with non essential
amino acids

4. Protein metabolism

5. Protein metabolism

6. Metabolism of Amonia(NH3)
 Ammonia is liberated in the metabolism of AA & other
nitrogenous compounds and is toxic to the body
 Mammals including man convert ammonia to non-toxic urea
for easy excretion
 Urea is synthesized in liver (Urea cycle/Kreb’s-Henseleit cycle)
and transported to kidneys for excretion
 Urea synthesis is a 5-step cyclic process with 5 distinct
enzymes( first 2 enzymes in mitochondria & rest in cytosol)

7. Ammonia metabolism

8.  All enzymes invariably lead to a build-up in blood ammonia along with other
metabolites depending on the enzyme defect
 The clinical symptoms associated with all the defects are more or less the same which
includes vomiting, lethargy, irritability, ataxia, and mental retardation
Ammonia metabolism

9. Blood urea – Clinical Importance
 Normal blood urea concentration is 10-40 mg/dl
 Elevation in blood urea maybe classified into:-
1. Pre-renal : increased protein breakdown leading to negative
nitrogen balance in conditions like prolonged fever, diabetic coma,
thyrotoxicosis, leukemias
2. Renal : disorders like acute glomerulonephritis, chromic nephritis
& nephrosclerosis
3. Post-renal : due to obstruction of urinary tract in conditions like
tumours, stones & enlargement of prostate gland
Ammonia metabolism

10. Metabolism of individual amino acids
Protein metabolism

11. Metabolism of glycine
Protein metabolism

13. Glycine metabolism

14.  Estimation of serum creatinine(along with blood urea)is
used as a diagnostic test for assessing kidney function
 Normal concentration of serum creatinine in man is 0.6-1.0
mg/dl
Glycine metabolism

15. Metabolism of
phenylalanine & tyrosine
Protein metabolism

17.  NNNNNnnjbhjuyyfhgy
4-Malylacetoacetate
Neonatal
tyrosinemia
Metabolism of aromatic amino acids
4-fumarylacetoacetate

18. Phenylketonuria
 Accumulation of phe in tissues and blood ,results in increased
excretion in urine
 Phe is diverted to alternate pathways resulting in excessive
production of phenylpyruvate, phenylacetate &
phenylglutamine
 Clinically manifest as mental retardation, failure of growth,
seizures & tremors
 T/t by maintaining normal plasma range(1-2 mg/dl) by intake
of food with low phe content
Metabolism of aromatic amino acids

19. Alkaptonuria(black urine)
 Caused by defect of enzyme homogentisate oxidase
 Homogentisate accumulates in tissues,blood & excreted in
urine
 Homogenisate gets oxidized to quinones which produce
black/brown pigment alkapton(responsible for black urine)
 Alkapton deposits in tissues,bone,organs resulting in
ochronosis
 T/t by low phe content in diet
Metabolism of aromatic amino acids

20. Metabolism of aromatic amino acids

21. Functions of catecholamines
 Norepinephrine & epinephrine regulate carbohydrate & lipid
metabolism by stimulating the degradation of
triacylglycerol & glycogen
 Increase in blood pressure
 Dopamine & norepinephrine serve as neurotransmitters in
brain & autonomic nervous system

22. Parkinson’s disease
 Characterised by muscular rigidity , tremors, expressionless
face, lethargy & involuntary movements
 Caused due to decreased production of dopamine
Metabolism of aromatic amino acids

23. Melanin synthesis
• Albinism is an inborn error
which manifests as
generalised
hypopigmentation due to
lack of synthesis of
melanin pigment
• Most common cause of
albinism is a defect in the
enzyme tyrosinase
Metabolism of aromatic amino acids

24. Metabolism of aromatic amino acids

25. Metabolism of tryptophan
Protein metabolism

26. Trp metabolism

27. Trp metabolism

28. Trp metabolism

29. Functions of serotonin
 Regulates regulation of cerebral activity(excitation) as a
neurotransmitter
 Results in smooth muscle contraction in bronchioles &
arterioles as a vasoconstrictor
 Controls behavioural patterns, sleep, blood pressure, and
body temperature
Trp metabolism

30. Functions of melatonin
 Melatonin is a hormone synthesized in the pineal gland
 It also acts as a neurotransmitter
 It is basically involved in circadian rhythms or diurnal
variations (24 hour cyclic process) of the body and thus plays
a significant role in sleep and wake process
Trp metabolism

31. Disorders
 Hartnup’s disease : defective intestinal absorption of
tryptophan leading to pellagra like symptoms(since trp is
responsible for niacin synthesis)
 Argentaffinoma/Malignant carcinoid syndrome :
uncontrolled growth of serotonin secreting cells in GIT
(almost 60% of trp is utilized for serotonin synthesis unlike
normal 1%) which manifest in the form of respiratory distress,
sweating, hypertension,etc. The estimation of 5- HIA in urine
is used in its diagnosis
Trp metabolism

32. Metabolism of sulphur amino
acids
(methionine,cysteine,cystine)
Protein metabolism

33. Metabolism of sulphur amino acids

34. Metabolism of sulphur amino acids

35. Disorders
 Cystinuria : Defective reabsorption of cysteine, ornithine,
arginine, lysine(COAL) in the renal tubules
 Cystinosis : Impaired cystine utilization due to defect in the
lysosomal function
 Homocystinuria : Deficiency of cystathione β synthase
which leads to elevation of homocysteine in blood(normal
<15 µ mol/l) and predisposes the individual to coronary
artery diseases(aggregation of LDL ,interference with
collagen cross-links), thrombosis, osteoporosis & very
often mental retardation
Metabolism of sulphur amino acids

36. Metabolism of branched
chain amino acids
(valine,isoleucine &
leucine)
Protein metabolism

37. Metabolism of branched chain amino acids
Acetyl Co-A Dehydrogenase
Branched chain amino acid transaminase
Alpha keto-acid dehydrogenase enzyme complex

38. Metabolic defects
 Maple syrup urine disease/branched chain ketonuria : Urine
smells like maple syrup or burnt sugar-hence the name
 Enzyme defect : defect of α-keto acid dehydrogenase blocks
conversion of keto acids to respective thioesters
 Complications: impairment in transport & function of other AAs
,reduced protein biosynthesis ,competitive inhibition of
glutamate dehydrogenase
 Symptoms: acidosis, lethargy, convulsions, mental retardation,
coma & finally death within one year of birth
 Diagnosis & treatment: Diagnosed by enzyme analysis or
presence of branched amino & keto acids in urine. Treatment
is to feed a diet with low or no content of branched AAs along
constant monitoring of plasma levels
Metabolism of branched chain amino acids

39. Metabolism of histidine,
proline, arginine,
glutamate & glutamine
Protein metabolism

40.  Histidine , arginine & proline all three are metabolized to give the same
end product i.e., glutamate
 Glutamate-besides being converted to glutamine-is involved in synthesis
of GLUCOSE, AMMONIA & certain special products
GLUTAMATE
GLUTAMINE
GABA
CARBOXY
GLUTAMATE
Metabolism of glycogenic amino acids
Purine
pyrimidine
Proteins NH3 Urea
Detoxification
Amino sugars

41. Metabolism of glycogenic amino acids
Histidine, on decarboxylation, gives the corresponding amine-Histamine
Hydrolase

42. Arginine & Proline degradation
The following enzymes are
involved:-
1 – Arginase
2 – Ornithine aminotransferase
3 – Pyrroline 5 carboxylate
reductase
4 – Proline oxidase
5 – Glutamate semi-aldehyde
dehydrogenase
6 - Glutaminase
7– Glutamate dehydrogenase
GLUTAMINE
6
Metabolism of glycogenic amino acids

43. Disorders associated with
proline & arginine
 Hyperprolinemia type 1 : due to defect in the enzyme
proline oxidase(proline dehydrogenase)
 Hyperargininemia : due to defect of enzyme arginase
Metabolism of glycogenic amino acids

44. Nitric oxide synthesis & functions
Functions :
• Acts as vasodilator & causes
relaxation of smooth muscles
• Regulates blood pressure
• Inhibits platelet aggregation
• Acts as a neurotransmitter
• Mediates bacterial action of
macrophages
Metabolism of glycogenic amino acids

45. Synthesis & significance of
GABA
 GABA forms succinate which
enters TCA cycle
 Bypass route of glutamate to
enter TCA cycle , k/as GABA
SHUNT
 Major inhibitory
neurotransmitter of brain
 Opens chloride channels &
increases permeability of post-
synaptic membranes
 Decreased GABA levels cause
convulsions

46. One carbon metabolism
 Network of integrated metabolic pathways act together to
continuously supply single carbon units for various
biochemical reactions
 Single carbon units are methyl(-CH3) , hydroxymethyl (-
CH2OH), methylene(=CH2) , methenyl (-CH=), formyl (-
CH=O) , formimino (-CH=NH)
 Tetrahydrofolate(THF) is a versatile coenzyme that actively
participates in one carbon metabolism
 With regards to transfer of methyl groups from S-
adenosylmethionine , vitamin b12 is also involved
Protein metabolism

47. Generation & Utilization of one
carbon units
Protein metabolism

48. MCQs
 Hopkin’s-cole test: test for indole group of tryptophan
 Nitroprusside test: for sulfhydryl group of cysteine
 Glutamate is the major source of ammonia in kidney
 Energy values of carbohydrates(4Kcal/g), fat(9Kcal/g) &
protein(4Kcal/g)
 Daily required doses of carbohydrates(40gms), fat(70gms)
&proteins(60gms)
 100gms of protein excretes approximately 16.5gms of
nitrogen
Protein metabolism

49.  Biochemical tests for abnormal constituents of urine:
Albumin & globulin- heat coagulation test
Blood - benzidine test
Glucose - benedict’s test
Ketone bodies - rothera’s test
Bile salts - hay’s test , patternkofer’s test
Bile pigments - fouchet’s test, gmelin’s test
 Acetone, acetoacetate & β-hydroxy butyrate are known as
ketone bodies & are major fuel source of brain during
prolonged starvation
Important notes for MCQs

50. THANK YOU