Conversion of

Amino acids into

Non-protein
Nitrogenous
Compounds
Dr. Contessa S. Tac-an
Glycine

• Heme synthesis
• Synthesis of purines  forms positions 4,
5, 7 of the purine ring
• Constituent of glutathione
• Conjugates with cholic acid to form
glycocholic acid
• Conjugates with benzoic acid to form
hippuric acid
• Synthesis of creatine
Alanine

• Carnosine - is a ß-alanyl dipeptide

that occurs in human
skeletal muscle.
• Anserine - also a ß-alanyl dipeptide
- derived from the diet
- occurs in skeletal muscle
characterized by rapid
contractile activity.
Structure of Carnosine
Structure of Anserine
 Carnosine & Anserine

Functions:
1. Activate myosin ATPase
activity.
2. Chelate copper and enhance
copper uptake.
Cont.

Synthesis: Carnosine synthetase

ß-alanine + L-histidine + ATP 

Carnosine + AMP + PPi

Carnosine N-methyltransferase
Carnosine + SAM  SAH
+ Anserine
Cont.

Degradation:
Carnosinase

Carnosine  ß-Alanine + L-

Histidine

• Carnosinase deficiency - heritable

d/o characterized by persistent
carnosinuria.
 Homocarnosine

• CNS dipeptide
• Related structurally &metabolically
to carnosine but is present in human
brain at levels 100x higher than
carnosine levels
• Synthesis in brain tissue is catalyzed
by carnosine synthetase
Structure of Homocarnosine
Serine, threonine & tyrosine

• Phosphorylation (by protein

kinases) & dephosphorylation
(by protein phosphatases) of
ser, thr & tyr serve important
regulatory functions.
Serine

• Biosynthesis of sphingosine
• Purines & pyrimidines 
ß-carbon of ser provides methyl
groups of thymine (& of choline)
and of carbons 2 & 8 of purines.
Methionine

• Its activated form, SAM (S-adenosyl

methionine) is the principal source of
methyl groups in the body.
• Biosynthesis of 3-diaminopropane
portions of the polyamines, spermine
and spermidine.
Cysteine

• Urinary sulfate arises from the

oxidation of L-cysteine. (Sulfur of
methionine contributes to urinary
SO4 indirectly, via cysteine.
• Precursor of thioethanolamine
portion of CoA
• Converted to Taurine, that
conjugates with bile acids such as
taurocholic acid
Histidine

• Decarboxylation of histidine forms

histamine, catalyzed by aromatic L-
amino acid decarboxylase or
histidine decarboxylase.
• Other histidine compounds include:
ergothioneine, carnosine, and
dietary anserine.
Synthesis of Histamine
Structure of ergothioneine
Arginine

• Arginine - formamidine donor for

creatine synthesis
• Conversion, via ornithine, to
putrescine, spermine & spermidine.
• Precursor of nitric oxide (NO), w/c is
a neurotransmitter, smooth muscle
relaxant & vasodilator.
Arginine

NO synthase

L-Arginine + O2 + NADPH 

L-Citrulline + NO

• Precursor of polyamines, spermine

And spermidine, w/c function in cell
proliferation and growth.
 Spermine & Spermidine

• Growth factors for cultured cells.

• Stabilization of intact cells,
subcellular organelles &
membranes.
• Pharmacologic doses of polyamines
are hypothermic and hypotensive.
• Associate w/ polyanions such as
DNA & RNA
• Stimulate DNA & RNA synthesis
Cont.

• DNA stabilization
• Packaging of DNA in bacteriophage
• Exert diverse effects in protein
synthesis
• Inhibit protein kinases

Polyamine biosynthesis catalyzed

by ornithine decarboxylase.
 Polyamine biosynthesis

• L-ornithine - precursor of
putrescine portion of spermine &
spermidine

• SAM - precursor of
diaminopropane portion
Cont.

Enzymes:
1. Ornithine decarboxylase & SAM
decarboxylase - inducible enzymes
w/ short half-lives
2. Spermine & Spermidine synthases
- are neither inducible nor
unusually labile enzymes.
Ornithine decarboxylase

• Half life 10 mins.

• Ten- to 200-fold increase in its
activity after administration to
cultured cells of GH, corticosteroids,
testosterone or EGF
SAM decarboxylase

• Cofactor: pyruvate
• Half life 1-2 hours
• Responds to promoters of cell
growth
• Inhibited by decarboxylated SAM
• Activated by putrescine
 Polyamine degradation
• Polyamine oxidase, of liver peroxisomes,
oxidizes spermine to spermidine;
subsequently oxidizes
spermidine to putrescine.
• Putrescine oxidizes to NH4 + CO2.
• Both aminopropane is converted to ß-
aminopropionaldehyde.

Major fraction of putrescine & spermidine

are excreted in urine as conjugates
(acetyl derivatives).
Tryptophan

• Forms serotonin
Synthesis/Reactions:
1. Hydroxylation of trp to 5-OHtrp,
catalyzed by liver tyrosine
hydroxylase
2. Decarboxylation of 5-OHtrp forms
serotonin(5-hydroxytryptamine)
Synthesis of Serotonin
 Serotonin

• Potent vasoconstrictor
• Stimulator of smooth muscle
contraction
• Catabolism initiated by monoamine
oxidase-catalyzed oxidative
deamination to 5-
hydroxyindoleacetate, excreted in
the urine (2-8mg/d)
Cont.

• Malignant carcinoid increases

serotonin production.
• Catabolites detected in the urine
include N-acetylserotonin
glucuronide and 5-
hydroxyindoleaceturate.
• Reduced synthesis of niacin (Vit.
B3), causing pellagra.
Serotonin forms melatonin

Reactions:
• N-acetylation
• O-methylation

Melatonin - taken up by all tissues

(incl. brain); rapidly metabolized by
hydroxylation at position 6, then
conjugated w/ SO4 or glucuronic acid.
Trp metabolites

• Excreted in urine and feces

• Principal normal urinary catabolites
are 5-hydroxyindoleacetate and
indole-3-acetate.
Tyrosine
• Biosynthesis of melanins, catalyzed by tyrosine
hydroxylase.
• Neuronal cells convert tyrosine to epinephrine
and norepinephrine
• Dopamine synthesis, via dopa decarboxylase
(B6PO4 as cofactor)
• Norepinephrine synthesis catalyzed by
dopamine ß-oxidase(Vit. C and copper
dependent enzyme)
• Methylation of NE (adrenal medulla) catalyzed
by phenylethanolamine-N-methyltransferase,
forms epinephrine
• Precursor of T3 and T4.
Synthesis of cathecolamines
 ALBINISM
• Defective melanin biosynthesis
• Hypomelanosis due to heritable defects
in eye and skin melanocytes
• Oculocutaneous albinism
• Forms:
1. Tyrosine hydoxylase negative albinos –
lack all visual pigment
-- hair bulbs fail to convert
tyrosine to pigment; melanocytes
contain unpigmented melanosomes
Cont.

2. Tyrosine hydroxylase positive

albinos – w/ some visible pigment &
white-yellow to light tan hair.
-- melanocytes w/ lightly
pigmented melanosomes.
3. Ocular albinism – AR & X-linked
trait.
X-linked ocular albinism –retinas w/
mosaic pattern of pigment
distribution.
 Creatine biosynthesis

• Derived from glycine, arginine &

methionine
• Transfer of guanidino group from
arginine to glycine, forming
guanidoacetate(glycocyamine);
occurs in kidney
• Methylation of guanidoacetate by
SAM in the liver
Cont.

• Creatine and phosphocreatine are

present in muscle, brain & blood.
• Forms creatinine (creatine
anhydride) in muscle, from creatine
PO4 by dehydration & loss of
phosphate
• 24 hr creatinine excretion in urine is
constant from day to day &
proportionate to muscle mass
L-glutamate
• Biosynthesis of -Aminobutyrate
(GABA), via decarboxylation of L-
glutamate catalyzed by glutamate
decarboxylase(B6PO4 cofactor)
present in CNS
• Addtition:
Putrescine can be converted to
GABA, either by deamination (by
diamine oxidase) or via N-acetylated
intermediates.
Cont.
• GABA degradation
GABA transaminase
GABA  succinate semi-
aldehyde
• Succinate semialdehyde may
undergo either:
1. Reduction to -hydroxybutyrate
2. Oxidation to succinate  to CO2 &
H2O