Specialized products from Amino acids

Part-2
Learning Objectives:
Specialized products(other than heme) formed from amino
acids and their biomedical importance
-- Creatine & creatinine
-- Catecholamines
-- Melanin
-- Serotonin
-- Other well known compounds

Reference:
Ferrier, D.R.: Lippincott's Illustrated Reviews Biochemistry, 6
th
edition,
Wolters Kluwer/Lippincott Williams and Wilkins. Chapter 21 (P. 285 290)



CREATINE

Synthesis of creatine requires 3 amino acids :
Glycine, Arginine & S-adenosyl methionine
(SAM)

Creatine Creatine P.
ATP ADP

Creatine phosphate acts as high energy
reservoir in muscle
Creatine kinase
Significant creatine excretion in urine is
observed in certain muscle disorders

Creatinine is the end product of creatine
catabolism (non enzymatic)
Creatinine is a normal constituent of urine
Determination of creatinine level in plasma is an
important investigation in kidney diseases
Example: Increase of plasma creatinine is a
notable feature seen in renal failure
CATECHOLAMINES:
Synthesized from the amino acid Tyrosine
TYROSINE

DOPA (Dihydroxy Phenylalanine)

DOPAMINE
Vit.C
NOREPINEPHRINE

EPINEPHRINE

TYROSINE HYDROXYLASE
DOPA DECARBOXLASE
DOPAMINE - HYDROXYLASE
METHYL TRANSFERASE
SAM
SAH
O
2
O
2
CO
2
PLP
Tetrahydrobiopterin
Catecholamines are synthesized in:
Adrenal Medulla, Brain & Sympathetic nervous
system (post ganglionic fibres)

Epinephrine & Norepinephrine regulate certain
metabolic pathways as well as blood pressure
Dopamine functions as neurotransmitter in
brain & involved in cognition, motivation,
behavioral changes etc
Parkinsons disease (a neurodegenerative
disorder) is caused by lack/decreased production
of dopamine Possibly due to loss of dopamine
producing cells
Epinephrine and Norepinephrine undergo
catabolism to form:
Vanillylmandelic Acid (VMA), which is excreted
in urine
Similarly dopamine is catabolized to form
Homovanillic acid
The enzymes involved in the degradation of
these catacolamines are;

Catechol O Methyl transferase (COMT)
Monoamine Oxidase (MAO)

Pheochromocytoma is a neuroendocrine tumor
of the Adrenal medulla
Excessive amounts of catecholamines are
secreted, usually epinephrine & norepinephrine

Symptoms: High blood pressure , palpitation,
anxiety, headache

In this condition the patients excrete excess VMA
in urine (Hence VMA is a Biochemical tumor
marker in Pheochromocytoma)

THYROID HORMONES:
Tyrosine residues of the protein Thyroglobulin,
present in Thyroid gland, undergo Iodination to
form two types of thyroid hormones;
THYROXINE (T
4
)
TRIIODOTHYRONINE (T
3
)
The above two hormones contain 4 and 3 iodide
residues, respectively

MELANIN:
Melanin is the pigment present in animal tissues, especially skin ,
hair & eyes. Synthesized from tyrosine in melanocytes




*MELANIN POLYMERS




Tyrosine DOPA Dopaquinone




* MELANIN POLYMERS





Tyrosinase is a copper containing enzyme, converts tyrosine to DOPA & again DOPA to dopaquinone


Albinism

Characterized by either partial or complete absence of melanin in skin, hair & eyes. Tyrosinase negative
oculocutaneous albinism (also called as complete albinism) is as a result of deficiency of tyrosinase. In
addition to hypopigmentation the affected individuals exhibit visual defects, photophobia & prone to
skin cancers

Albinism may be inherited by autosomal dominant or autosomal recessive patterns
Ocular albinism is X linked disorder










TYROSINASE
Cysteine Glutathione
Serotonin:

Formed from Tryptophan

Serotonin is an important neurotransmitter

Highest conc is seen in Intestinal mucosal cells

Functions: Pain perception and regulation of sleep,
temperature as well as blood pressure
TRYPTOPHAN
Tetrahydrobiopterin O
2


Dihydrobiopterin
5-OH TRYPTOPHAN


CO
2
5-OH TRYPTAMINE (SEROTONIN)
ACETYL CoA

CoA
N-ACETYL SEROTONIN

SAM

SAH

MELATONIN


TRYPTOPHAN HYDROXYLASE
5-OH TRYTOPHAN DECARBOXYLASE PLP
5 hydroxy indole acetic acid (5-HIAA) is the end
product formed by the catabolism of Serotonin
Serotonin 5-HIAA

Metastatic Carcinoid (also called as
Argentaffinoma) is an example for cancer of
argentaffin cells of abdominal cavity
This produces, large amount of Serotonin
Symptoms: flushing, diarrhea, wheezing,
abdominal pain
The subjects excrete high conc. of
5- Hydroxy Indole Acetic Acid (5-HIAA) in urine


Monoamine Oxidase (MAO)
In general, the enzyme Monoamine Oxidase
(MAO) is required for the catabolism of different
neurotransmitters (derived from amino acids)
such as Serotonin, Catecholamines, Histamine
etc

Thus MAO plays an important role in regulation
of the conc. of those neurotransmitters

MAO inhibitors are used as antidepressant
drugs
Histamine:
Formed from histidine upon decardoxylation
(using PLP dependent enzyme)
Mediate allergic & inflammatory reactions
Stimulate gastric HCl secretion
Causes vasodilatation
Neurotransmitter

Histidine Histamine

CO
2
Histidine decarboxylase

PLP
Glutathione:
It is a tripeptide made up of three amino acids:
Glutamate, Cysteine & Glycine

Importance mainly as an antioxidant

Nitric oxide (NO):
Synthesized from the amino acid Arginine by the
action of enzyme nitric oxide synthase

NO acts as a signaling agent One of the
important function vasodilatation