Relationships in different parts of the nephron between enzymes of glycerol metabolism and the metabolite changes which result from large glycerol loads.

Abstract

Glycerol metabolism in 9 defined parts of rat nephron was studied by measurement of glycerol kinase and observation of effects of large glycerol loads on related metabolites and on ATP and total adenylate. Glycerol kinase with glycerol as substrate was highest in the proximal convoluted tubule, slightly lower in straight portions, 20 to 25 times lower in distal segments, and almost indetectable elsewhere. With dihydroxyacetone as substrate, enzyme distribution differed little except for 30% lower activity in proximal convoluted segments. Methods of measurement with 10-40 ng of freeze-dried tissue are described. Glycerol loads produced large accumulations of glycerol 3-phosphate in proximal segments and in distal convoluted tubules. In the control nephron, fructose bisphosphate plus triose phosphates was 1 times higher in distal straight and convoluted segments than in proximal segments. Increases with glycerol loads were limited to proximal straight tubules (2-fold) and the thin limb area (60%). Glucose-6-P increased 3-fold in the late portion of the proximal straight tubule but not elsewhere. ATP and total adenylate were markedly depleted no phosphorylated intermediates accumulated. Levels of Pi were decreased in whole cortex and medullar following glycerol loads.