MODULATION OF GLYCINE-SERINE INTERCONVERSION BY TCA AND GLYCOLYTIC-INTERMEDIATES IN NORMOXIC AND HYPOXIC PROXIMAL TUBULES

Glycine-serine interconversion is important to numerous metabolic proc esses and serine release by the kidney. Incubation of freshly isolated rat renal proximal tubules with 5 mM glycine 75% C-13-labelled in the 2-position resulted in C-13-labelled incorporation into serine of 69 mu mol.g protein(-1) (+/-14, n=16) at 20 min. Addition of 5 mM glucose , 5 mM lactate, 1 mM alanine, 1 mM butyrate and 1 mM glutamate increas ed C-13-label incorporation into serine to 173 mu mol.g protein(-1) (/-32, n=4) at 60 min, 50% greater than tubules incubated with 5 mM gly cine alone (P<0.05). The increase was prevented by hypoxia. Reoxygenat ion for 20 min restored the rate of incorporation of C-13-label into s erine. The fraction of unlabelled serine remained similar to 47% at 20 , 40 and 60 min in each group. The results indicate that in the presen ce of oxygen, TCA and glycolytic intermediates stimulate serine synthe sis via the glycine cleavage complex and serine hydroxymethyltransfera se pathways and not the phosphorylated pathway. In addition, significa nt serine production occurs from an unidentified source, which is also tightly coupled to glycine metabolism. Both in the presence and absen ce of added TCA and glycolytic intermediates, glycine was the principl e source of the methylene group in methylene tetrahydrofolate.