Tryptophan Metabolism It is an essential Amino Acid containing indole ring metabolized mainly in two pathways 1.Major pathway Kynurenine pathway 90% 2. Minor Pathway Serotonin pathway 10% Melatonin pathway The major pathway occurs in the liver and the main metabolic final product is Nicotinic Acid Niacin) (B- Complex) require vit. B6 as a cofactor A m I n o A c I d S M E T A B O L I S M

It has been estimated that 60 mg of tryptophan in food protein is converted to 1mg of nicotinic acid inhuman A m I n o A c I d S M E T A B O L I S M

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Tryptophan Metabolism Kynurenine pathway (major 90%) B6 A m I n o A c I d S M E T A B O L I S M

Serotonin pathway(Minor) A m I n o A c I d S M E T A B O L I S M MAO

Ist step in minor pathway is hydroxylation of tryphtophan To 5 hydroxy tryptophan. Tryphtophan is further decarboxylated into 5hydroxytryptamin 5HT. 5HT is a potent vasoconstrictor and regarded as neurotransmitter. 5HT is converted by MAO into 5HIAA. A m I n o A c I d S M E T A B O L I S M

Another minor pathway is Melatonin Pathway This pathway of tryptophan metabolism occur in pineal body by N acetylating process using the enzyme acetylase to convert tryphtophan into melatonin which is regarded as neurotransmitter. The final end product of Tryptophan are 1. Nicotinic Acid. 2. Serotonin. 3. Melatonin. A m I n o A c I d S M E T A B O L I S M

Melatonin synthesis and secretion from pineal gland is controlled by light. It involves in circadian rhythm or diurnal variation (24hrs cyclic process),it play a significant role in sleep and wake process.. It performs a neurotransmitter function. A m I n o A c I d S M E T A B O L I S M

Melatonin is derived from serotonin within the pineal gland and the retina, where the necessary N- acetyltransferase enzyme is found. The pineal parenchymal cells secrete melatonin into the blood and cerebrospinal fluid. Synthesis and secretion of melatonin increases during the dark period of the day and is maintained at a low level during daylight hours. A m I n o A c I d S M E T A B O L I S M

This diurnal variation in melatonin synthesis is brought about by norepinephrine secreted by the postganglionic sympathetic nerves that innervate the pineal gland. This leads to increased levels of cAMP, which in turn activate the N-cetyltransferase required for melatonin synthesis. Melatonin functions by inhibiting the synthesis and secretion of other neurotransmitters such as dopamine and GABA A m I n o A c I d S M E T A B O L I S M

Disorders of Tryptophan Metabolism (Metabolic diseases of Tryptophan) Hartnup Disease: # It is autosomal recessive inherited disease. #The defect is in the cellular transport of tryptophan &failure of its absorption. #Defective intestinal absorption with defective reabsorption in the kidney. #The above defect results in increase excretion of tryptophan and indole derivatives in urine. # The above defect results in low level of blood Tryptophan. A m I n o A c I d S M E T A B O L I S M

#Low level of Tryptophan in blood lead to defective production of nicotinic acid (niacin) through the kynurenine pathway ( major pathway). #Defective production of niacin leads to pellagra (DDD)unless there is sufficient amount of nicotinic acid supplied in the diet. Diagnosis : By Amino acid Analysis in the Low level of level of tryphtophan &its indole derivatives excreted in the urine. Pellagra:(DDD):Dermatits, skin lesion begins as photosensitivity occur symmetrically on face,neck, wrist with erythema and scaling. Dementia with intermittent cerebellar ataxia. Diarrhea. A m I n o A c I d S M E T A B O L I S M

The defect can be cured by giving mg of nicotinic acid daily A m I n o A c I d S M E T A B O L I S M Normally 1% of tryptophan is converted to serotonin. These cells synthesize the biologically active amine (5HT). It is a potent vasoconstrictor and stimulator of smooth muscle contraction.

Most of the serotonin is metabolized by oxidative deamination by the enzyme monoamine oxidase(MAO). MAO inhibitor used as Antidepressant drug that lead to accumulation of serotonin and nor adrenalin in nerve endings that help in treatment of depression. A m I n o A c I d S M E T A B O L I S M

Carcinoid Syndrome: # It is acquired disease due to a tumor of argentaffin cells of the intestine. #Commonest site is ileum and appendix. # May be benign or malignant. #Excessive secretion of serotonin. A m I n o A c I d S M E T A B O L I S M

Most of tryptophan taken by the diet is diverted to be metabolized by argentaffin cells through the serotonin pathway instead of kyneurinine pathway. 1%_________________60% Normal Malignant tumor. Biochemically: abnormally high level of 5HT. High level of 5HIAA in urine. >25mg/day. Sign of niacin deficiency due to diversion from kyneurinine pathway to serotonin pathway. A m I n o A c I d S M E T A B O L I S M

Symptoms: 1.Flushing of the face. 2.Diarrhea. 3.Attack of Abd. Pain. 4.Symptoms of pellagra. A m I n o A c I d S M E T A B O L I S M

Sulphur containing Amino Acids Cystine Cysteine Methionine CH3 S ( CH2)3 CHNH2 COOH Methionine A m I n o A c I d S M E T A B O L I S M

Methionine is essential,it serves as precursor for the synthesis of cysteine and cystine.Cysteine and cystine are interconvertable Methionine and cysteine present in proteins. The sulfur containing amino acids are almost an exclusive dietary source of sulfur to the body. A m I n o A c I d S M E T A B O L I S M