The hydrolysis of glycerol-3-phosphate into glycerol in cardiac tissue: possible consequences for the validity of glycerol release as a measure of lipolysis

Abstract

Glycerol release has been generally accepted as an index of lipolysis in the intact heart. The glycerol moiety of glycerol-3-phosphate (glycerol-3-P) is incorporated into triacylglycerols, which are then hydrolysed with release of glycerol. This study investigates the possibility that glycerol may be derived directly from glycerol-3-P instead of passing through the triacylglycerol pool. The cardiac capacity for hydrolysis of glycerol-3-P into glycerol was determined in homogenates of rat hearts. Glycerol-3-P hydrolysis activity in homogenates increased with decreasing pH. The activity was approximately four times higher at pH 5.0 than at pH 7.2 (0.94 +/- 0.11 and 0.25 +/- 0.03 mumol.g wet weight-1.min-1 respectively). The substrate concentration at which half-maximal glycerol-3-P hydrolysis activity was reached did not significantly differ at pH 5.0 and pH 7.2 (4.2 +/- 1.1 mM and 2.9 +/- 1.0 mM respectively). In the intact heart, the pH and substrate conditions found under ischaemia are favourable for direct conversion of glycerol-3-P into glycerol. The glycerol-3-P hydrolysis activity measured in vitro was sufficiently high to account for glycerol production in the ischaemia heart. However, the lack of a stoichiometric relation between cardiac glycerol-3-P and glycerol levels in ischaemia indicates that production of glycerol cannot be explained solely by hydrolysis.

Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic β-cells and hepatocytes

“…The possibility of Gro3P hydrolysis in mammalian cells (34) and fish (11,35) was previously considered, but no clear evidence could be obtained. In a recent work, it has been suggested that, in liver, there is a NADH/NAD + ratio-dependent direct formation of glycerol from Gro3P, generated by high carbohydrate intake, particularly under conditions of mitochondrial aspartateglutamate carrier isoform-2 (i.e., citrin) deficiency; however, no enzyme for this conversion was suggested (36).…”

Glycerol loss to water exceeds glycerol catabolism via glycerol kinase in freeze-resistant rainbow smelt (Osmerus mordax)

“…The direct dephosphorylation of the G3P to glycerol has been proposed to be the pathway used in smelt to directly produce glycerol (5,8), as it is the case in some algae and yeasts producing high amounts of glycerol in response to environmental stresses (23,37). Activity of such an enzyme has been suggested in oxygenlimited rat heart and brain, although neither the protein nor the transcript have been identified in a vertebrate (4,22). Isolation and characterization of such an enzyme would be of interest, as it would open a new avenue of research concerning the role of glycerol in vertebrates.…”

Myocardial ischemia-reperfusion and cardioprotection: a study with microdialysis in a porcine model

“…Another metabolic fate of glucose during myocardial ischemia may be to the accumulation of glucose-6-phosphate and glycerol-3-phosphate (Jeffrey 1992). The G-3-P may further be hydrolyzed and recovered as glycerol (de Groot 1994). The decrease of pyruvate to undetectable levels during hours of cold storage, observed in study IV, has also been demonstrated for pig livers (Nowak 2002).…”

“…In myocardial ischemia, accumulation of glycerol precedes the rise in fatty acid intermediates, suggesting cycling of triacylglycerols (van Bilsen 1989). During ischemia, G-3-P produced by glycolysis may be directed to the esterification of fatty acids into triacylglycerols or hydrolyzed to glycerol (de Groot 1994). Ischemic induced activity of phospholipases may degrade phospholipids (Ford 2002), with theoretically glycerol release.…”