Synthesis of Backbone of TAGs Phospholipids Mostglycerol 3 phosphate comes from siphoning off dihydroxyacetone phosphate DHAP from glycolysis va glycerol 3 phosphate dehydrogenase some glycerol 3 phosphate is made from glycerol Vla glycerol kinase minor pathway in liver kidney fatty acy group is activated by formation of the fatty acyl CoA then transferred to ester linkage with L glycerol 3 phosphate Glucose glycolysis H2COM 6 0 o M2 0 p o II Dihydroxyacetoned HeCOM MCON I I HzCOM Glycerol Phosphatidic acid 2 a c 2 of the glycerol molecule Intermediate acid To conserve space in subsequentfigures both fatty acyl groups of glycerols pnosprate productwith only one esterified fatty acyl group is lysophosphatidic m glycerophospholipids Iall three acyl groups of triacylglycerols are dehydrogenase shown projecting to the right NADI phosphate i Synthesis of Phosphophatidic Acid Occurs before TAGS Phosphatidic acid precursor to TAGs phospholipids fatty acids attached by acyltransferases releases CoA Advantage of making phosphatidic acid Itcan then be made into triacylglycerol OR phospholipid Phosphatidic Acid can be modified to form phospholipids or TAGS 4 R Phosphatidic acid phosphatase lipin removes intrcm Phosphatein the 3 phosphate from the phosphatidic acid attachment of icanincinaraareainconosphatidis acid is the precursor of both triacylglycerine 3rd carbon is then acylated with a 3rd fatty acid 12anden yields triacylglycerol yields 1 2 diacylglycerol Glycerophospholipids glycerophospholipids Mechanisms for head group attachment in phospholipid synthesis r k re Meet i I4 c 0 1 0 Glycerol 3 phosphate H2COH notto L Glycerol 3 phosphate R c00 areene I a cyl transferase roroarere acyltransferaseI 2 ohisnote COA SH Phosphatidic add 0 Regulation of Triacylglycerol Synthesis by Insulin Insulin results in stimulation of triacylglycerol Synthesis Dietary carbohydrates Pletary proteins Lack of insulin results In Increased lipolysis Increased fatty acid oxidation sometimes to ketones if citric acid cycle intermediates coxaloacetate thatreactwith acetyl CoA are depleted insulin Glucose Amino acids failure to synthesize fatty acids Insulin stimulates conversion ofdietary carbohydrates proteins to fat Individuals with diabetes mellitus either lack insulin or are sensitive to it This results in diminished fatty acid synthesis acetyl CoA arsing from catabolism of carbohydrates proteins is shunted Instead to ketone body production People In fatty acids Triacylglycerols Acetyl CoA Retonebodies acetoacetate In diabetes p B hydroxybutyrate increased acetone severe ketosis smell of acetone so the condition is Triacylglycerol Breakdown Resynthesis sometimes mistaken for drunkenness Triacylglycerol Cycle Adipose tissue Blood Liver Lipoprotein Glycerol pase Elycerol A create a futile cycle 75 of 3 fatty acids ffAs released by lipolysis are re esterified to form TAGs rather than be used for fuel Some recycling occurs in adipose tissue Triacylglycerol M Some FFAs from adipose cells are transported to the liver I Although distribution between the 2 paths may vary overall remade into TAG and redeposited in adipose cells Triacylglycerol Fatty Glycerol 3 phosphate Fuel for ISSUES Glycerol 3 phosphate the percentage of FFAs being esterified remains at75 Mammals triacylglycerol molecules broken down tresynthesized during starvation Some fatty pods released by lipolysis of triacylglycerol in adipose tissue pass Into bloodstream Remainder is Phosphoenolpyruvate Pyruvate pyruvate carboxylase Glyceroneogenesis Pep carboxykinase Lipolysis stimulated by glucagon or epinephrine Iglycolysis Is Inhibited oxaloacetate up by the liver used in triacylglycerol synthesis The triacylglycerol contains similar steps of gluconeogenesis used for resynthesis of triacylglycerol Some fatty acids released into the blood are used for energy In muscle some are taken formed in the liver is transported in the blood back to adipose tissue where the fatty acid is released by extracellular lipoprotein lipase taken up by adipocytes reesterified into triacylglycerol Dihydroxyacetone phosphate multistep glycerol 3 phosphate dehydrogenase H2C OH ric on 9 macnorate Triacylglycerol synthesis DHAP is notreadily available to make glycerol 3 phosphate Adipose cells don thave glycerol kinase to make glycerol 3 phosphate on site Converts pyruvate DHAP an abbreviated version of gluconeogenesis In the liver adipose tissue