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Specialized products from Amino acidsPart-2Learning 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, 6th 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 muscleCreatine 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 urineDetermination of creatinine level in plasma is an important investigation in kidney diseasesExample: 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 HYDROXYLASEDOPA DECARBOXLASEDOPAMINE - HYDROXYLASEMETHYL TRANSFERASESAMSAHO2O2CO2PLPTetrahydrobiopterinCatecholamines are synthesized in:Adrenal Medulla, Brain & Sympathetic nervous system (post ganglionic fibres)

Epinephrine & Norepinephrine regulate certain metabolic pathways as well as blood pressureDopamine 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 cellsEpinephrine and Norepinephrine undergo catabolism to form:Vanillylmandelic Acid (VMA), which is excreted in urineSimilarly dopamine is catabolized to form Homovanillic acidThe 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 medullaExcessive 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 (T4) TRIIODOTHYRONINE (T3)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

TYROSINASECysteineGlutathione10Serotonin:

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 11 TRYPTOPHAN Tetrahydrobiopterin O2

Dihydrobiopterin 5-OH TRYPTOPHAN

CO2 5-OH TRYPTAMINE (SEROTONIN) ACETYL CoA

CoA N-ACETYL SEROTONIN SAM

SAH MELATONIN

TRYPTOPHAN HYDROXYLASE5-OH TRYTOPHAN DECARBOXYLASEPLP5 hydroxy indole acetic acid (5-HIAA) is the end product formed by the catabolism of SerotoninSerotonin 5-HIAA

Metastatic Carcinoid (also called as Argentaffinoma) is an example for cancer of argentaffin cells of abdominal cavityThis produces, large amount of SerotoninSymptoms: 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 reactionsStimulate gastric HCl secretionCauses vasodilatation Neurotransmitter

Histidine Histamine

CO2Histidine decarboxylase PLPGlutathione: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