Renal metabolism of amino acids in vivo: studies on serine and glycine fluxes.
The pathway of serine synthesis by the rat kidney has been investigated in vivo by measuring the net flux in the presence and absence of specific inhibitors of the glycine cleavage system, phosphoenol-pyruvate carboxykinase and gamma-glutamyltranspeptidase. In normal animals serine release was 705 +/- 187 nmol X min-1 X animal-1, whereas glycine uptake was only 28% of this value. Inhibition of the glycine cleavage system (cysteamine infusion) resulted in a reversal of glycine flux with no change in serine production. In similar experiments with mercaptopicolinate serine release was decreased by 55% with no change in glycine removal. AT-125, a potent inhibitor of gamma-glutamyltranspeptidase, had no effect on renal serine and glycine fluxes. In chronically acidotic rats serine synthesis was unchanged, but there were significant increases in the uptake of glutamine (fourfold) and glycine (2.5-fold). Infusion of cysteamine into these animals caused a 50% decrease in serine release with a significant reversal of the glycine flux. Infusion of mercaptopicolinate had effects similar to those observed in normal animals. These results show that renal serine synthesis can occur by both the phosphorylated-intermediate pathway and serine hydroxymethyltransferase in vivo. Furthermore, they demonstrate that glycine can contribute significantly to ammoniagenesis during acidosis.
D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001784:Blood Gas Analysis; D003543:Cysteamine / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012694:Serine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors
D000596:Amino Acids; D010848:Picolinic Acids; D012694:Serine; D003543:Cysteamine; C008363:3-mercaptopicolinic acid; D005723:gamma-Glutamyltransferase; D005998:Glycine