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Pathway Description
Glycerolipid Metabolism
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2023-10-29
The glycerolipid metabolism pathway describes the synthesis of glycerolipids such as monoacylglycerols (MAGs), diacylglycerols (DAGs), triacylglycerols (TAGs), phosphatidic acids (PAs), and lysophosphatidic acids (LPAs). The process begins with cytoplasmic 3-phosphoglyceric acid (a product of glycolysis). This molecule is dephosphorylated via the enzyme glycerate kinase to produce glyceric acid. Glyceric acid is then transformed to glycerol (via the action of aldehyde dehydrogenase and aldose reductase). The free, cytoplasmic glycerol can then be phosphorylated to glycerol-3-phosphate through the action of glycerol kinase. Glycerol-3-phosphate can then enter the endoplasmic reticulum where glycerol-3-phosphate acyltransferase (GPAT) may combine various acyl-CoA moieties (which donate acyl groups) to form lysophosphatidic (LPA) or phosphatidic acid (PA). The resulting phosphatidic acids can be dephosphorylated via lipid phosphate phosphohydrolase (also known as phosphatidate phosphatase) to produce diacylglycerols (DAGs). The resulting DAGs can be converted into triacylglycerols (TAGs) via the addition of another acyl group (contributed via acyl-CoA) and the action of 1-acyl-sn-glycerol-3-phosphate acyltransferase. Extracellularly, the triacylglycerols (TAGs) can be converted to monoacylglycerols (MAGs) through the action of hepatic triacylglycerol lipase. In addition to this cytoplasmic route of glycerolipid synthesis, another route via mitochondrial synthesis also exists. This route begins with glycerol-3-phosphate, which can be either derived from dihydroxyacetone phosphate (DHAP), a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells) or from glycerol itself. Glycerol-3-phosphate in the mitochondria is first acylated via acyl-coenzyme A (acyl-CoA) through the action of mitochondrial glycerol-3-phosphate acyltransferase to form lysophosphatidic acid (LPA). Once synthesized, lysophosphatidic acid is then acylated with another molecule of acyl-CoA via the action of 1-acyl-sn-glycerol-3-phosphate acetyltransferase to yield phosphatidic acid. Phosphatidic acid is then dephosphorylated to form diacylglycerol. Specifically, diacylglycerol is formed by the action of phosphatidate phosphatase (also known as lipid phosphate phosphohydrolase) on phosphatidic acid coupled with the release of a phosphate. The phosphatase exists as 3 isozymes. Diacylglycerol is a precursor to triacylglycerol (triglyceride), which is formed in the addition of a third fatty acid to the diacylglycerol by the action of diglyceride acyltransferase. Since diacylglycerol is synthesized via phosphatidic acid, it will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position. When the body uses stored fat as a source of energy, glycerol and fatty acids are released into the bloodstream. Fatty acids, stored as triglycerides in humans, are an important and a particularly rich source of energy. The energy yield from a gram of fatty acids is approximately 9 kcal/g (39 kJ/g), compared to 4 kcal/g (17 kJ/g) for carbohydrates. Since the hydrocarbon portion of fatty acids is hydrophobic, these molecules can be stored in a relatively anhydrous (water-free) environment. Fatty acids can hold more than six times the amount of energy than sugars on a weight basis. In other words, if you relied on sugars or carbohydrates to store energy, then you would need to carry 67.5 lb (31 kg) of glycogen to have the energy equivalent to 10 lb (5 kg) of fat.
References
Glycerolipid Metabolism References
Schade SZ, Early SL, Williams TR, Kezdy FJ, Heinrikson RL, Grimshaw CE, Doughty CC: Sequence analysis of bovine lens aldose reductase. J Biol Chem. 1990 Mar 5;265(7):3628-35.
Pubmed: 2105951
Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.
Pubmed: 16305752
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.
Pubmed: 19393038
Roy R, Ordovas L, Taourit S, Zaragoza P, Eggen A, Rodellar C: Genomic structure and an alternative transcript of bovine mitochondrial glycerol-3-phosphate acyltransferase gene (GPAM). Cytogenet Genome Res. 2006;112(1-2):82-9. doi: 10.1159/000087517.
Pubmed: 16276094
Mistry DH, Medrano JF: Cloning and localization of the bovine and ovine lysophosphatidic acid acyltransferase (LPAAT) genes that codes for an enzyme involved in triglyceride biosynthesis. J Dairy Sci. 2002 Jan;85(1):28-35. doi: 10.3168/jds.S0022-0302(02)74049-6.
Pubmed: 11860120
Bengtsson-Olivecrona G, Olivecrona T, Jornvall H: Lipoprotein lipases from cow, guinea-pig and man. Structural characterization and identification of protease-sensitive internal regions. Eur J Biochem. 1986 Dec 1;161(2):281-8. doi: 10.1111/j.1432-1033.1986.tb10444.x.
Pubmed: 3536511
Senda M, Oka K, Brown WV, Qasba PK, Furuichi Y: Molecular cloning and sequence of a cDNA coding for bovine lipoprotein lipase. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4369-73. doi: 10.1073/pnas.84.13.4369.
Pubmed: 2885834
Yang CY, Gu ZW, Yang HX, Rohde MF, Gotto AM Jr, Pownall HJ: Structure of bovine milk lipoprotein lipase. J Biol Chem. 1989 Oct 5;264(28):16822-7.
Pubmed: 2674142
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000039
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