Synthesis, storage and degradation of myocardial triglycerides.
In the mammalian myocardium, an active triglyceride synthesis pathway is operating, (re)esterifying activated fatty acids from endogenous or exogenous sources, with the glycolytically derived three-carbon intermediates dihydroxyacetone-phosphate and glycerol-3-phosphate by the so-called Kennedy pathway. The seven enzymes of triglyceride synthesis are membrane bound and located at the sarcoplasmic reticulum. The first enzyme in the glycerol-3-phosphate pathway, glycerol-3-phosphate acyltransferase, is proposed to be rate limiting for triglyceride formation. This microsomal enzyme is regulated by phosphorylation (inactiycation)-dephosphorylation (activation) coupled to the beta-receptor--adenyl cyclase--protein kinase system. Additional regulatory steps in triglyceride formation are the reactions catalyzed by the microsomal phosphatidic acid phosphatase and diglyceride acyltransferase. Intracellular triglycerides occur as free floating cytosolic droplets, membrane-bound particles and lipid-filled lysosomes. No consensus exists about the metabolically active portion of myocardial triglycerides. Various lipases have been proposed to be involved in endogenous lipolysis: the lysosomal acid, microsomal and soluble neutral triglyceride, intracellular lipoprotein lipases and the microsomal di- and monoglyceridase. It has been acknowledged that the bulk of the intracellular neutral lipase represents the precursor of vascular lipoprotein lipase. The presence of a neutral lipase, as distinct from lipoprotein lipase, in the rat heart was recently advocated. Endogenous lipolysis is a hormone-sensitive process. Hormone-sensitivity may involve direct alteration of enzyme activity by protein phosphorylation-dephosphorylation but is also dependent on the removal rate of product fatty acids, since feedback inhibition is a common property of all lipases in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Stam
H
H
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
Schoonderwoerd
K
K
Hülsmann
W C
WC
D000818:Animals; D001693:Biological Transport, Active; D005227:Fatty Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D009206:Myocardium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism*
D005227:Fatty Acids; D014280:Triglycerides; D011494:Protein Kinases; D008049:Lipase