Triglyceride metabolism (Homo sapiens)
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Description
Fatty acids derived from the diet and synthesized de novo in the liver are assembled into triglycerides (triacylglycerols) for transport and storage. Synthesis proceeds in steps of conversion of fatty acyl-CoA to phosphatidic acid, conversion of phosphatidic acid to diacylglycerol, and conversion of diacylglycerol to triacylglycerol (Takeuchi & Reue 2009).
Hydrolysis of triacylglycerol to yield fatty acids and glycerol is a tightly regulated part of energy metabolism. A central part in this regulation is played by hormone-sensitive lipase (HSL), a neutral lipase abundant in adipocytes and skeletal and cardiac muscle, but also abundant in ovarian and adrenal tissue, where it mediates cholesterol ester hydrolysis, yielding cholesterol for steroid biosynthesis. The hormones to which it is sensitive include catecholamines (e.g., epinephrine), ACTH, and glucagon, all of which trigger signaling cascades that lead to its phosphorylation and activation, and insulin, which sets off events leading to its dephosphorylation and inactivation (Kraemer & Shen 2002).
Hydrolysis of triacylglycerol to yield fatty acids and glycerol is a tightly regulated part of energy metabolism. A central part in this regulation is played by hormone-sensitive lipase (HSL), a neutral lipase abundant in adipocytes and skeletal and cardiac muscle, but also abundant in ovarian and adrenal tissue, where it mediates cholesterol ester hydrolysis, yielding cholesterol for steroid biosynthesis. The hormones to which it is sensitive include catecholamines (e.g., epinephrine), ACTH, and glucagon, all of which trigger signaling cascades that lead to its phosphorylation and activation, and insulin, which sets off events leading to its dephosphorylation and inactivation (Kraemer & Shen 2002).
The processes of triacylglycerol and cholesterol ester hydrolysis are also regulated by subcellular compartmentalization: these lipids are packaged in cytosolic particles and the enzymes responsible for their hydrolysis, and perhaps for additional steps in their metabolism, are organized at the surfaces of these particles (e.g., Brasaemle et al. 2004). View original pathway at Reactome.</div>
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Phosphorylation of human HSL has not been studied in detail, so the human reaction is inferred from the well-studied rat one. By BLAST alignment, human HSL residues 649 and 650 correspond to rat serines 659 and 660.
Dephosphorylation of human HSL has not been studied in detail, so the human reaction is inferred from the well-studied rat one.
The interaction of human CGI-58 and perilipin on the lipid particle surface has not been studied in detail, so the human reaction is inferred from the well-studied mouse one. The observation that humans homozygous for CGI-58 mutations suffer from Chanarin-Dorfman Syndrome, characterized by the abnormal accumulation of triacylglycerol droplets in most tissues (Lefevre et al. 2001), provides indirect evidence that human and mouse CGI-58 proteins have similar functions.
HSL-mediated triacylglycerol hydrolysis in humans has not been studied in detail, so the human reaction is inferred from the well-studied rat one.
The human reaction is inferred from the well-studied rat one.
Dimerization of human HSL has not been studied in detail, so the human reaction is inferred from the well-studied rat one.