Metabolism
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A severe sunburn-like rash and unusual urinary metabolites
Key points from this exercise:
The amino acid transporters in cell membranes are group specific. Rather than having a separate transporter for each amino acids, they are transported in groups depending on the chemical nature of the side-chain: acidic, basic or neutral.
The same amino acid transporters are involved in absorption of amino acids from the small intestine, re-absorption in the kidney of amino acids filtered at the glomerulus, and in transport of amino acids across the blood-brain barrier.
Proteolytic enzymes secreted into the intestinal lumen do not hydrolyse dipeptides and tripeptides.
Dipeptides and tripeptides resulting from hydrolysis of dietary proteins in the small intestine are absorbed intact into the intestinal mucosal cells, then hydrolysed to their constituent amino acids.
The transport of dipeptides and tripeptides is by transporters that are separate from those for amino acids.
In addition to its role in protein synthesis and the synthesis of the neurotransmitter serotonin (5-hydroxytryptamine), tryptophan provides much, or even most, of the nicotinamide required for synthesis of the coenzymes NAD and NADP.
Unabsorbed amino acids in the intestinal lumen are substrates for intestinal bacterial fermentation. The products of bacterial metabolism can be absorbed and excreted unchanged or after onward metabolism (e.g. conjugation with sulphate, glucose of glucuronic acid) in the urine. Some of the products of tryptophan metabolism by bacteria may be neurotoxic.
This case was originally described in 1956 by Baron DN, Dent CE, Harris H et al. Hereditary pellagra-like skin rash with temporary cerebellar ataxia, constant renal amino-aciduria, and other bizarre biochemical features. Lancet 271, 421-428. The patient was called Eddie Hartnup, and the condition is now known as Hartnup disease or Hartnup syndrome. Study of this patient provided the early evidence that amino acids were transported by proteins that have specificity for groups of among acids (acidic, basic, neutral), as well as early evidence that dipeptides are absorbed from the intestinal lumen by a separate mechanism, and undergo hydrolysis to the free amino acids intracellularly.
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