Enzymes of Glucose Metabolism and of the Citrate Cleavage Pathway in Adipose Tissue of Normal and Diabetic Subjects

Abstract

Enzyme activities operative in glucose degradation and citrate cleavage pathway were studied in the adipose tissue of twenty-four patients with adult-onset diabetes and normal body weight, aged 59+/-9 years, and twenty-four matched controls. In normal tissue, type II (heat-inactivated) hexokinase moderately predominated over type I (heat-resistant). 6-Phosphofructokinase had an extremely low activity, which was by far the lowest among the ten glycolytic enzyme activities investigated, and which therefore might greatly limit the glycolytic rate. The level of glucose-6-phosphate dehydrogenase and phosphogluconate dehydrogenase (decarboxylating) was elevated above that occurring in other tissues. This, especially if considered together with the low 6-phosphofructokinase activity, would suggest a major role of pentose cycle in glucose degradation. Of the citrate cleavage pathway enzymes, ATP citrate-lyase, although having a lower activity than malate dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), was readily measurable, which contrasts with previous data by others. This finding is consistent with the occurrence of lipogenetic capacity in human adipose tissue. In diabetic tissue, there was a decreased activity, both on a protein and on a wet-weight basis, of enzymes concerned with the glucose entry into metabolic pathways, namely hexokinase (both type I and, especially, type II) and pentose cycle dehydrogenases, as well as of pyruvate kinase. This could be connected with the defective glucose utilization by adipose tissue in diabetes. Beside the above-mentioned dehydrogenases, malate dehydrogenase (decarboxylating) (NADP) was also diminished. The reduction of these NADPH-forming enzymes, which supply reducing equivalents for fatty acid synthesis, would suggest a depressed lipogenesis.

Increase of Docosahexaenoic Acid Production by Schizochytrium sp. Through Mutagenesis and Enzyme Assay

“…Two additional NADPH forming metabolic cycles were known to occur [22]. One was the hexose monophosphate pathway (HMP), which consisted of the action of G6PDH; the other was the citrate cleavage pathway, which consisted of the sequential action of ACL and ME.…”

Effect of high‐fat diet on the expression of proteins in muscle, adipose tissues, and liver of C57BL/6 mice

“…Its activity was found to be significantly lower in adipose tissue of fat compared to lean mice [49]. Belfiore et al [50] also observed a reduction in NADPH-forming enzymes, including malate dehydrogenase, in adipose tissue of diabetic subjects, which suggested depressed lipogenesis. Moreover, downregulation of malate dehydrogenase in BAT is in agreement with the findings of a previous study, where we observed a 3-fold lower expression of this enzyme in BAT of genetically obese Lep ob / Lep ob vs. lean mice [51].…”

Platelet Function and Acetyl-Coenzyme A Metabolism in Type 1 Diabetes Mellitus

“…The increase in HX activity in diabetic platelets indicates that, unlike in the liver and adipose tissue, the expression of the enzyme in these cells is independent of insulin (26). The lack of significant correlation between HX activity and fructosamine or HbA 1c concentrations in diabetic individuals suggests that prolonged hyperglycaemia may not be a predominant factor affecting enzyme expression (Tables 1, 4, 7).…”