Glycine Pathway Research Articles

Urine and calculus amino acids in the different types of urolithiasis.

Urinary amino acid excretion levels were estimated by paper chromatography in 15 control subjects and 27 stone formers classified according to stone type: (a) 15 cases with calcium oxalate stones, either pure or mixed with calcium phosphate and/or uric acid; (b) 6 cases with pure uric acid stones and (c) 6 cases with magnesium-ammonium phosphate stones, either pure or mixed with ammonium urate, also the free amino acid contents of the calculi of different types were estimated. The data revealed that there was a significant decrease in the amino acid excretion in all stone formers; the individual amino acid patterns varied according to the type of stone formed. This decrement in amino acid excretion could be attributed to: (a) a metabolic defect in the pathway of glycine, especially in the calcium oxalate cases; (b) the precipitation and/or adsorption of the free amino acids on the material of the calculi, which is demonstrated in 10 calculi, and (c) to a lesser extent to bacterial infection.

Inhibition of the glycine cleavage system: hyperglycinemia and hyperglycinuria caused by valproic acid.

Elevated amounts of glycine in serum and urine were demonstrated in patients and rats receiving the antiepileptic drug valproic acid. The hyperglycinuria in the patients was correlated to the dose of the anticonvulsant. The activity of the glycine cleavage system, the major catabolic pathway of glycine, in liver homogenates from rats treated with valproic acid was clearly reduced. Further in vitro studies on intact rat liver mitochondria and the solubilized glycine cleavage system showed that valproic acid and valproyl-CoA significantly inhibited the glycine cleavage enzyme complex. It was concluded that the hyperglycinemia and hyperglycinuria seen in patients and rats during the administration of valproic acid are due to the inhibition of the glycine cleavage system, most probably by valproic acid and/or valproyl-CoA.