Amino AcidTransport and Associated Hereditary

DisordersProf. Dr. Arzu SEVEN

• Mechanisms of active transport of amino acids and di-or tripeptides into intestinal epithelial cells are similar to those described for glucose uptake.

• At the brush border membrane Na dependent symporters mediating amino acid uptake are linked to ATP-dependent pumping out of Na at the contraluminal membrane

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• A similar H+-dependent symporter is present on the brush border surface for di- and tripeptide active transport into the cell.

• Na-independent transporters are present on the contraluminal surface, allowing facilated transport of amino acids to hepatic portal system.

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• At least 6 specific symporter systems have been indentified for the uptake of L-amino acids from the intestinal lumen

• These transport systems are also present in the renal tubules and defects in their molecular structure can lead to disease.

γ glutamyl cycle

• A metabolic cycle involving GSH as a carrier has been implicated in the transport of certain amino acids across the membranes in the kidney.

• Amino acid +GSH γ glutamyl amino acid+cysteine + glycine• Enzyme: γ glutamyltransferase (GGT)

located in plasma membrane• (γ glutamyl transpeptidase)

• This reaction helps transfer certain amino acids across the plasma membrane, amino acid is hydrolyzed and GSH resynthesized from cysteinylglycine.

• This cycle is present in the plasma membrane at renal tubular cells and bile ductule cells, and in the endoplasmic reticulum of hepatocytes.

• γ_GT is released into the blood from hepatic cells in various hepatobiliary diseases.

Neutral Amino Aciduria:Hartnup Disease

• Hartnup disease is a genetic defect in the Na-coupled transporter that normally mediates absorption of neutral amino acid from the lumen of the small intestine and the proximal tubule.

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• In the kidney, the inability to reabsorb neutral amino acids from the ultrafiltrate leads to their excretion in urine (neutral amino aciduria).In the intestine, the defect results in malabsorption of dietary neutral amino acids.

• Clinical symptoms are those one would expect for a deficiency of tryptophan with pellagra-like features, which is an expression of the decreased availability of tryptophan for conversion to nicotinamide.

Cystiniuria

• Autosomal recessive disorder of intestinal absorption and proximal tubular reabsorption of dibasic amino acids.

• No defect in cysteine metabolism per se

• Cysteine remains in the urine

• Oxidizes to its disulfide form (cystine)

• Cystine is relatively insoluble, tends to precipitate in the urinary tract-kidney stone

• Treatment-by restriction of dietary intake of methionine (a biosynthetic precursor of cysteine) + high fluid intake to keep the urine dilute + drugs that may convert cysteine to a more soluble compound