37. Conversion of amino acids to specialized products – tryptophan (NAD, serotonin, melatonin), tyrosine (sysnthesis of thyroid hormones, catecholamines, melanins). Products of glutamine and glutamate metabolism. The γ -glutamyl cycle. Glutathione as an antioxidant and participant in the metabolism of xenobiotics.

Introduction

This topic covers how tryptophan and tyrosine are converted into neurotransmitters, hormones and pigments, the role of glutamate and glutamine as carriers of nitrogen and as precursors, and the function of glutathione, including its synthesis and transport by the γ-glutamyl cycle. It follows the topics on transamination and essential amino acids.

Tryptophan: serotonin, melatonin and NAD

Tryptophan is hydroxylated by tryptophan hydroxylase to 5-hydroxytryptophan, which is decarboxylated to serotonin. Serotonin acts as a neurotransmitter in the brain and as a hormone-like signal in the gut and in platelets. In the pineal gland, serotonin is acetylated and then methylated to melatonin. Synthesis is increased in darkness through sympathetic noradrenergic signalling, which is how melatonin signals the length of the night. Tryptophan is also the source of NAD through the kynurenine pathway, which yields quinolinate and then NAD. About 60 mg of tryptophan gives about 1 mg of niacin equivalent.

Tyrosine: catecholamines, thyroid hormones and melanin

Tyrosine is hydroxylated by tyrosine hydroxylase to DOPA. This is the rate-limiting step of catecholamine synthesis. DOPA is decarboxylated to dopamine, which is hydroxylated in vesicles to norepinephrine. In the adrenal medulla, norepinephrine is methylated to epinephrine. In the thyroid, tyrosyl residues of thyroglobulin are iodinated to monoiodotyrosine and diiodotyrosine, which couple to form \mathrm{T}_{3} and \mathrm{T}_{4}. In melanocytes, tyrosinase oxidises tyrosine through DOPA to melanin.