Modulation of glycine-serine interconversion by TCA and glycolytic intermediates in normoxic and hypoxic proximal tubules

摘要

Glycine-serine inlereonversion is important to numerous metabolic processes and serine release by the kidney. Incubation of freshly isolated rat renal proximal tubules with 5 mM glycine 75% l3C-labelled in the 2-position resulted in C-labelled incorporation into serine of 6°juinol.g protein (± 14, n - 16) at 20 min. Addition of 5 mM glucose, 4 mM lactate, 1 mM alanine, 1 mM butyrate and 1 mM glutamate increased 'C-label incorporation into serine to 173 /tmolg protein"1 (±32, =4) at 60 min, 50% greater than tubules incubated with 5 mM glycine alone (P < 0.05). The increase was prevented by hypoxia. Reoxygenation for 20 min restored the rate of incorporation of C-lubel into serine. The fraction of unlabelled serine remained 47% at 20, 40 and 60 min in each group. The results indicate that in the presence of oxygen, TCA and glycolytic intermediates stimulate serine synthesis via the glycine cleavage complex and serine hydroxyinethyltransferase pathways and not the phosphorylated pathway. In addition, significant serine production occurs from an unidentified source, which is also tightly coupled to glycine metabolism. Both in the presence and absence of added TCA and glycolytic intermediates, glycine was the principle source of the methylene group in methylene tetrahydrofolate.