The document discusses the conversion of various amino acids into specialized products and metabolic pathways. It notes that amino acids serve as precursors for many nitrogenous compounds like porphyrins, neurotransmitters, hormones, creatine, purines and pyrimidines. It then elaborates on the specialized products and metabolic roles of individual amino acids such as alanine, arginine, cysteine, glycine, histidine, methionine, serine, tryptophan and tyrosine. Non-α amino acids like β-alanine, β-aminobutyrate and γ-aminobutyrate are also discussed. Key pathways and products mentioned include glutathione, creatine, catecholamines,

1. Conversion of Amino
Acids into Specialised
Products
Apeksha Niraula
Junior Resident-II

2. Contents
 Introduction
 Amino acids as a precursor for many
numerous non-nitrogenous compounds.
 Elaboration of Specialised 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.
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.

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

11. Metabolic Role of Cysteine
 Glucogenic:Cysteine is catabolised 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’.

12. Glycine
 Many drugs, drug metabolites, and other compounds with
carboxyl groups are excreted in the urine as glycine conjugates.
 Specialised Products :
 Glycine Conjugates: Glycocholic Acid, Taurocholic
Acid
 Heme
 Glutathione
 Purines
 Creatine

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

15. Heme

17. Glutathione (GSH)
 Glutathione (GSH), present in plants, animals, and some
bacteria, often at high levels, acts as a redox buffer.
 Derived from glycine, glutamate, and cysteine.
 Carboxyl group of glutamate is activated by ATP to form
an acyl phosphate intermediate, which is then attacked
by the α- amino group of cysteine.


18.  A second condensation reaction follows, with the -
carboxyl group of cysteine activated to an acyl
phosphate to permit reaction with Glycine.
 The oxidized form of glutathione (GSSG), produced in
the course of its redox activities, contains two
glutathione molecules linked by a disulfide bond.
 Glutathione probably helps maintain the sulfhydryl
groups of proteins in the reduced state and the iron
of heme in the ferrous (Fe2+)state.

19. Glutathione (GSH)
Reduced

20.  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

21. Glycine Contribution to Purine Structure

22.  Creatine phosphate/ Phosphocreatine
Found in muscle, a high-energy compound that can
reversibly donate a phosphate group to adenosine
diphosphate 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

23. 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.

24.  The amount of creatinine produced is related to
muscle mass.
 The level of creatinine excretion (clearance rate)
is a measure of renal function

26. Degradation of Creatine
 Creatine and Creatine phosphate spontaneously cyclize
at a slow but constant rate to form creatinine, which is
excreted in the urine.
 The amount of creatinine excreted is proportional to the
total creatine phosphate content of the body, and thus can
be used to estimate muscle mass.
 Any rise in blood creatinine is a sensitive indicator of
kidney malfunction.
 An Adult male excretes 15mmol of Creatine per day.

28. 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 brain hypothalamus varies in
accordance with a circadian rhythm.

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

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

32.  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.

33. 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.

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

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

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

40. 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.

42. 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

43. 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.

44.  Serotonin is synthesized from tryptophan, which is
hydroxylated in a reaction analogous to that catalyzed by
Phenylalanine Hydroxylase.
 The product, 5-hydroxytryptophan, is decarboxylated to
serotonin, which is also degraded by MAO.
 Serotonin has multiple physiologic roles, including pain
perception, and regulation of sleep, temperature, and blood
pressure.

47. Melatonin
 Hormone of Pineal body.
 Synthesised from Serotonin.

48. Tyrosine
 Thyroid Hormones Synthesis
 Catecholamines
 Melanin

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

51. 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.

52. 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.


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

57. Degradation of Catecholamines
 The Catecholamines are inactivated by oxidative deamination
catalyzed by monoamine oxidase(MAO), and by O-methylation
carried out by Catechol-O-Methyltransferase.
 The two reactions can occur in either order.
 The aldehyde products of the MAO reaction are oxidized to the
corresponding acids.
 The metabolic products of these reactions are excreted in the
urine as Vanillylmandelic acid from Epinephrine and
Norepinephrine, and Homovanillic acid from Dopamine.

59.  Parkinson’s disease Neurodegenerative Disorder
 Insufficient Dopamine Production.
 Idiopathic loss of Dopamine producing cells in
the brain.
 Levodopa Most Common Treatment.
 Over production of Dopamine in the brain may be linked to
psychological disorders such as Schizophrenia.

60. 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.

61.  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

65. Biosynthesis of Catecholamines and Serotonin
from Tyrosine and Tryptophan and metabolism
of Serotonin to Melatonin

66. Non- α Amino Acids
Non--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

67. 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

68. β- Alanyl Dipeptides
 Carnosine, Homocarnosine and Anserine

69. 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

71. References:
 Harper’s Illustrated Biochemistry, 29th Edition
 Lippincott’s Illustrated Biochemistry, 5th
Edition
 Lehninger’s Principles of Biochemistry, 5th
Edition

72. Thank You