Disease relevance of Gyk

• Database searches show no homology to other known proteins from mammalian origin, however, the amino-acid sequence in the middle portion of ASTP protein shows 48% homology to glycerol kinase from Escherichia coli [1].
• A recombinant adenovirus containing the bacterial glycerol kinase gene (AdCMV-GlpK) was constructed and used to express the enzyme in islets and INS-1 cells, resulting in insulin secretion in response to glycerol [2].
• We have reinvestigated this point and find that rat islets and the well differentiated insulinoma cell line INS-1 contain negligible glycerol kinase activity [2].
• Proportional activities of glycerol kinase and glycerol 3-phosphate dehydrogenase in rat hepatomas [3].
• With the single exception of Morris hepatoma 16, which had unusually high glycerol 3-phosphate dehydrogenase activity, the activities of glycerol 3-phosphate dehydrogenase and glycerol kinase were highly correlated in normal livers and hepatomas (r = 0.97; P less than 0.01) [3].

High impact information on Gyk

• By inducing GyK, TZDs markedly stimulate glycerol incorporation into triglyceride and reduce FFA secretion from adipocytes [4].
• The 'futile' fuel cycle resulting from expression of GyK in adipocytes is thus a novel mechanism contributing to reduced FFA levels and perhaps insulin sensitization by antidiabetic therapies [4].
• This is surprising, as standard textbooks indicate that adipocytes lack GyK and thereby avoid futile cycles of triglyceride breakdown and resynthesis from glycerol and FFAs [4].
• Here we report that TZDs, acting as ligands for the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-gamma, markedly induce adipocyte glycerol kinase (GyK) gene expression [4].
• The importance of such a fatty acid re-esterification process in the control of lipid homeostasis is highlighted by the existence of a second thiazolidinedione-induced pathway involving glycerol kinase [5].

Biological context of Gyk

• Effects of cyclic AMP, glucocorticoids and insulin on the activities of phosphatidate phosphohydrolase, tyrosine aminotransferase and glycerol kinase in isolated rat hepatocytes in relation to the control of triacylglycerol synthesis and gluconeogenesis [6].
• Exogenous glycerol kinase competed effectively with mitochondrially bound hexokinase for extramitochondrial ATP, with relatively low levels of glycerol kinase completely inhibiting phosphorylation of Glc.(ABSTRACT TRUNCATED AT 400 WORDS)[7]
• Glycerol kinase was found to associate with the hexokinase binding protein [8].
• These results are similar to in vitro kinetics of the glycerol kinase, except that K-i was found to be somewhat lower in the intact organ [9].
• (iv) With the binding of glycerol kinase to the mitochondria, it is possible to propose a metabolic pathway for glycerol oxidation to dihydroxyacetone phosphate by a combined action involving the enzyme, glycerol phosphate oxidase, and oxidative phosphorylation [8].

Anatomical context of Gyk

• There was an excellent correlation (r greater than 0.93) between changes in glycerol kinase and sn-glycerol-3-P acyltransferase activity and the capacity of hepatocyte monolayers to incorporate labeled glycerol into glycerolipids under all conditions studied [10].
• In this study, we examined whether adenoviral-mediated glycerol kinase (AdV-CMV-GlyK) expression in isolated rat pancreatic islets could introduce glycerol-induced proinsulin biosynthesis [11].
• We conclude that blood glycerol is a direct and important precursor for muscle triglyceride synthesis in rats, confirming the presence of functionally important amounts of glycerol kinase in skeletal muscle [12].
• Glycerol kinase activity was found in the particulate fraction of rat brain homogenates predominantly associated with mitochondria [13].
• Glycerol kinase activity in adipose tissue of obese rats and mice: effects of diet composition [14].

Associations of Gyk with chemical compounds

• Externally supplied glycerol did not affect glucose metabolism but externally added glucose interfered with glycerol metabolism in a way that suggests that the rate-limiting step is at the level of glycerol kinase [15].
• The inhibition was readily reversed by dilution or dialysis, by the addition of EDTA, and by incubating the inhibited enzyme with glycerol and glycerol kinase to convert the ATP to ADP [16].
• 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 [17].
• Cycloheximide (1 microM) reduced the insulin- and glucagon-dependent increases in sn-glycerol-3-P acyltransferase and glycerol kinase activity and glycerolipid biosynthesis [10].
• PUFA deficiency led to a 16% decrease in DHA metabolism owing to a 34% decrease in glycerol kinase activity; the significant decrease in the ATP/ADP ratio was accompanied by an increase in the fractional glycolytic flux [18].

Other interactions of Gyk

• The enzymatic activities of ATP-citrate lyase, acetyl CoA carboxylase, fatty acid synthetase, glycerol kinase and NAD-kinase decrease progressively when TAM was chronically administered [19].
• Phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase, succinate dehydrogenase, NADP(+)-linked malic enzyme, NADH fumarate reductase, malate dehydrogenase, and alpha-ketoglutarate dehydrogenase and glycerol kinase on the other hand had specific activities greater than 60 nanomoles/min/mg protein [20].

References