Sources- Harper , lehninger and lippincott

1. CONVERSION OF AMINO
ACIDS TO SPECIALIZED
PRODUCTS
DR. MANOJ ACHARYA
JUNIOR RESIDENT-I
BPKIHS

2. Overview
 Introduction
 Elaboration of Specialized Products of Individual Amino
Acids.

3.  Amino Acids : 1) Building Block of Proteins
2) Precursors of many
Nitrogenous containing compounds
 These molecules include:
Porphyrins, Neurotransmitters, Hormones, Creatine,
Purines, and Pyrimidines.

4. L-α Amino Acids
 Alanine
 Arginine
 Cysteine
 Glycine
 Histidine
 Methionine
 Serine
 Tryptophan
 Tyrosine
Non-α Amino Acids
 β- Alanine
 β- AminoIsobutyrate
 β- Alanyl Dipeptides
 γ- Aminobutyrate

5. Alanine
• Serves as a carrier of Ammonia and of the carbons of
Pyruvate from Skeletal Muscle to Liver via the Cori Cycle.
• Together with Glycine Constitutes a major function of the
free amino acids in Plasma.

6. Arginine
 Serves as a Nitrogen atoms in Urea Biosynthesis.
 Guanidino Group of Arginine is incorporated into Creatine.
 Following conversion to Ornithine Its Carbon
Skeleton becomes that of the Polyamines: Putrescine and
Spermine.

8. Cysteine
 Conversion of Cysteine to Taurine is by the Non-Heme Fe2+
Enzyme Cysteine Dioxygenase.
 L- Cysteine Decarboxylation Mercaptoethanolamine
Constituent of Coenzyme A

9. Three enzyme – catalyzed
reactions converts cysteine to
taurine

10. Metabolic Role of Cysteine
 Glucogenic: Cysteine is catabolized to Pyruvic acid
which is Glucogenic.
 Formation of Glutathione
 Formation of Taurine: Cysteine is utilised in the
formation of ‘Taurine’, which combines with cholic
acid obtained from degradation of cholesterol in
Liver to form Bile acid ‘Taurocholic acid’.

11. Glycine
 Many drugs, drug metabolites, and other compounds with
carboxyl groups are excreted in the urine as glycine
conjugates.
 Specialized Products :
I. Glycine Conjugates: Glycocholic Acid,
Taurocholic Acid
II. Heme
III. Glutathione
IV. Purines
V. Creatine

12.  Metabolites and pharmaceuticals excreted as water-
soluble glycine conjugates include Glycocholic acid and
hippuric acid formed from the food additive benzoate.

14. Glutathione (GSH)
 Glutathione (GSH), present in plants, animals, and some
bacteria, often at high levels.
 Derived from glycine, glutamate, and cysteine.
 Glutathione probably helps maintain the sulfhydryl
groups of proteins in the reduced state and the iron of
heme in the ferrous (Fe2+) state.

15. Glutathione (GSH)
Reduced

16.  Glutathione serves as a Reductant; is conjugated to
drugs to make them more water soluble
(Detoxification).
 Its redox function is also used to remove toxic
peroxides formed in the normal course of growth and
metabolism under aerobic conditions Reaction
catalyzed by Glutathione Peroxidase

17. Glycine Contribution to Purine Structure

18.  Creatine phosphate/ Phosphocreatine
Found in muscle, a high-energy compound that can
reversibly donate a phosphate group to adenosine
diphosphate(ADP) to form ATP.
 Provides a small but rapidly mobilized reserve of
high-energy phosphates used to maintain
the intracellular level of Adenosine triphosphate
(ATP) during the first few minutes of intense
muscular contraction.
Creatine

19. Synthesis of Creatine:
 Creatine is synthesized from Glycine and the Guanidino
group of Arginine, plus a methyl group from S-
adenosylmethionine.
 Creatine is reversibly phosphorylated to creatine
phosphate by Creatine kinase, using ATP as the
phosphate donor.
 The amount of creatinine produced is related to muscle
mass.
 The level of creatinine excretion (clearance rate) is a
measure of renal function

21. Histidine
 Decarboxylation of histidine by the pyridoxal 5'-phosphate-
dependent enzyme histidine decarboxylase forms Histamine.
Histamine.
 A biogenic amine that functions in allergic reactions and gastric
secretion.
 Histamine is present in all tissues.
 Its concentration in the hypothalamus of the brain fluctuates
with the circadian rhythm.

22.  Histidine compounds present in the human body
include Ergothioneine, Carnosine, and Anserine(γ-
Aminobutyryl Histidine).
 Carnosine ( β-Alanyl-histidine), Homocarnosine (β -
Aminobutyryl-Histidine) and Anserine are major
constituents of excitable tissues, brain, and
skeletal muscle.

24. Methionine
 NonProtein fate of Methionine: Conversion to S-Adenosyl
Methionine (SAM)
 SAM Synthesized from
Methionine and ATP.
Methionine and ATP
Methionine
Adenosyltransferase (MAT)
S - Adenosyl Methionine

25. • Human tissues contain three MAT isozymes.
MAT-1 & MAT-3 Liver
MAT-2 Non-Hepatic Tissues
• Severely Decreased Hepatic MAT-1 and MAT-3 activity
results in Hypermethionemia.
• If there is residual MAT-1/MAT-3 activity and MAT-2
activity is normal, a high tissue concentration of
methionine will assure synthesis of adequate amounts
of S-adenosylmethionine.

26. Metabolic fate of L-methionine
Stage 1: Activation of methionine and its
demethylation to form L-Homocysteine.
Stage 2: Conversion of L-homocysteine to L-
homoserine.
Stage 3: Degradation of L-homoserine to end
products L-propionyl-CoA and α-amino
butyrate.

28.  Methionine is “Glucogenic”:
Propionyl-CoA the end
product is glucogenic.
 Creatine formation
 Lipotropic function
 Polyamine synthesis
Metabolic Role of Methionine

30. Polyamines
 Putrescine , Spermidine , Spermine
 Ornithine (Formed from Arginine in Urea Cycle)
is a Precursor
 Functions:
 Cell Proliferation and Growth
 Putrescine--- Best Marker for Cell Proliferation
 Required as “Growth Factors” for Cultured
mammalian and bacterial cells

31. α-DifluoromethylOrnithine (DFMO)
Inhibitor of Ornithine Decarboxylase
 Used in T/t of African
Trypanosomiasis (Sleeping
sickness)

33. Serine
 Serine participates in the biosynthesis of sphingosine and of
purines and pyrimidines, where it provides carbons 2 and 8
of purines and the methyl group of thymine.
 Conversion of serine to Homocysteine is catalyzed by
Cystathionine β- synthase.
 Homocystinuria: genetic defects in cystathionine β -
synthase (heme protein) that catalyze the pyroidoxical 5
phosphate dependent condensation of serine with
homocysteine to form cystathionine.

34. Tryptophan
 Glucogenic and Ketogenic
 Nicotinic acid formation: Tryptophan rich diet has “sparing
effect” on niacin requirement in diet. 60 mg of
tryptophan can give rise to 1 mg of Niacin.
 Formation of Serotonin
 Formation of Melatonin

35. Serotonin
• Also called 5-hydroxytryptamine, is synthesized and
stored at several sites in the body.
• Largest amount of serotonin is found in cells of the
intestinal mucosa.
• Smaller amounts occur in the central nervous system,
where it functions as a neurotransmitter, and in
platelets.

37. Catabolism of serotonin

38. Melatonin
 Hormone of Pineal body.
 Synthesized from Serotonin.

39. Tyrosine
• Thyroid Hormones Synthesis
• Catecholamines
• Melanin

40. Neurotransmitters
EXCITATORY
 Acetylcholine
 Aspartate
 Dopamine
 Norepinephrine
 Epinephrine
 Histamine
 Glutamate
INHIBITORY
• GABA • Glycine

41. Catecholamines
 Norepinephrine is the principal neurotransmitter of
Sympathetic postganglionic endings.
 Catecholamines are stored in synaptic knobs of
neurons that secrete it.
 Norepinephrine and epinephrine are also synthesized
in the adrenal medulla.
 Tyrosine is transported into catecholamine-secreting
neurons and adrenal medullary cells where
catecholamine synthesis takes place.

42. Synthesis of catecholamines:
 The Catecholamines are synthesized from Tyrosine.
 Tyrosine Hydroxylated to form 3,4-
DihydroPhenylalanine (DOPA).
 Rate Limiting Step- Step catalyzed by Tyrosine
Hydroxylase
Tetrahyrobiopterin requiring enzyme.

43. DOPA
Decarboxylation
PLP
Dopamine
Dopamine β- Hydroxylase (Cu2+ containing
Enzyme)
Norepinephrine
Methylation (Methyl Donor- SAM)
Epinephrine

46. Degradation of Catecholamines

47. Melanin
 Tyrosine is the precursor of melanins that are produced
from Dopaquinone.
 The two primary melanins are Eumelanins, which are
dark pigments having a brown or black color, and
Pheomelanins that have red or yellow color.
 The yellow color of Pheomelanin pigments comes from
the sulfur in cysteine that is combined with
Dopaquinone.

48. Ratio of Eumelanin & Pheomelanin
Predicts the Dark Hair or Light Hair [Depending the
Distribution of Melanin-filled Granules along the Hair Shaft].
 Natural loss of Hair Result of Ageing when Melanin
Production in Human Melanocytes Shuts Down and these
cells are not replaced which occurs in Young Person

49. Non- α Amino Acids
Non- α amino acids present in tissues in a free form
include –
I. β - Alanine,
II. β- Aminoisobutyrate, and
III. γ - Aminobutyrate (GABA).
Alanine is also present in combined form in coenzyme A
and in the β -Alanyl dipeptides: Carnosine, Anserine and
Homocarnosine .

50. β -Alanine & β –Aminoisobutyrate
 Formed during catabolism of the pyrimidines Uracil and
Thymine,respectively.
 Traces of β -alanine also result from the hydrolysis of β
-alanyl dipeptides by the enzyme Carnosinase.
 β -Aminoisobutyrate also arises by transamination of
methylmalonate semialdehyde, a catabolite of L-
valine.

51. β- Alanyl Dipeptides
 Carnosine, Homocarnosine and Anserine
ATP + beta alanine ------> beta alanyl-AMP + Ppi
Beta alanyl-AMP + L-Histidine ------> Carnosine + AMP.
•Catalyzed by carnosine synthetase.
•Carnosinase (Carnosine hydrolase) – hydrolysis carnosine
to beta alanine and L-histidine.
•Homocarnosine:
- present in human brain.
- Synthesized by carnosine synthetase.

52. γ- Aminobutyrate
• GABA Inhibitory Neurotransmitter
• Alters Transmembrane potential differences.
• Formed by Decarboxylation of Glutamate by L-
Glutamate Decarboxylase.
Clinical Implications
• Rare Genetic Disorder of GABA Metabolism
includes a defective GABA Aminotransferase
Enzyme that participates in the catabolism of GABA

54. References:
 Harper’s Illustrated Biochemistry,
 Lippincott’s Illustrated Biochemistry,
 Lehninger’s Principles of Biochemistry.