BIOCHEMISTRY: METABOLISM OF TRYPTOPHAN & Carcinoid tumour

Metabolism of Tryptophan dealt in short with Carcinoid tumour

1. METABOLISM OF TRYPTOPHAN H ARITA PRAKASH REDDY FINAL YEAR MBBS AIMS,Mandya

2. TRYPTOPHAN AROMATIC,NEUTRAL ESSENTIAL AMINO ACID WITH INDOLE RING ESSENTIAL FOR GROWTH BIOLOGICALLY IMPORTANT SUBSTANCES PRODUCED : Alanine(glucogenic) 2. Acetyl – CoA (ketogenic) 3.Serotonin 4.Melatonin 5.Niacin & NAD+ 6.Hydroxy indole acetic acid (excretory product) 1890, Ernst Stadelmann discovered Tryptophan

3. TRYPTOPHAN KYNURENINE PATHWAY NICOTINIC ACID PATHWAY Kynureninase is dependent on PLP. Tryptophan oxidised by tryptophan pyrrolase( tryptophan dioxygenase ), a haemoprotein In Vit B6 deficiency, pathway blocked, niacin deficiency results in pellagra like symptoms Tryptophan catabolised to alanine ( enters glucose pathway) & acetoacetate( ketogenic pathway. Tryptophan is glucogenic and ketogenic Hydroxyanthranilate production dependent on PLP QPRT is rate limiting step 97% 3% Catabolic Pathways

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5. SEROTONIN MELATONIN Produced in brain, mast cells, platelets, argentaffin cells of GIT mucosa Part of serotonin released is taken up again RR – 50-200 ng/mL ( adult blood) SSRI, MAO inhibitors( iproniazid), tricyclic antidepressants >400ng/mL in carcinoid tumour Produced by pineal gland Associated with light-dark cycle, sleep – wake cycle, induces sleep, decreases respiratory rate & body temp. Acts as membrane receptor MT(1) & MT(2)

6. WHY CARBOHYDRATES INDUCE SLEEP ? Tryptophan causes aa traffic jam owing to bulky nature, When Carbohydrate rich diet is consumed, insulin secretion increases, lowering aa concentration in blood. Tryptophan easily reaches brain cells, generates serotonin to induce sleep.

7. PUTREFACTION OF TRYPTOPHAN : Intestinal bacteria putrefies Tryptophan to skatoxyl ( excreted in faeces) & Indican ( excreted in urine ) Indican ( potassium salt of indoxyl sulfate ) levels in urine – 4-20mg/day. Increased in Hartnup’s disease.