Fatty acid from glucose

Synthesis of Fatty Acids from Glucose After a person has ingested large amounts of sucrose, the glucose and fructose that exceed caloric requirements are transformed to fatty acids for triacylglycerol synthesis. This fatty acid synthesis consumes acetyl-CoA, ATP, and NADPH. How are these substances produced from glucose ... 

The formation of triglyceride from fatty acids and glycerol is often called lipogenesis. Another type of lipogenesis is the formation of fatty acids from glucose. To distinguish from the first, this is called de novo lipogenesis or DNL. 

B. The synthesis of fatty acids from glucose occurs in the cytosol, except for the mitochondrial reactions in which pyruvate is converted to citrate. Biotin is required for the conversion of pyruvate to oxaloacetate, which combines with acetyl CoA to form citrate. Biotin is also required by acetyl CoA carboxylase. Pantothenic acid is covalently bound to the fatty acid synthase complex as part of a phosphopantetheinyl residue. The growing fatty acid chain is attached to this residue during the sequence of reactions that produce palmitic acid. NADPH, produced by the malic enzyme as well as by the pentose phosphate pathway, provides reducing equivalents. Citrate, not isocitrate, is a key regulatory compound. 

Most mammalian cells have the capacity to synthesize fatty acids from glucose de novo in a pathway that uses products from glycolysis and two key cytosolic enzymes, acetyl-CoA carboxylase and fatty acid synthase (Chapter 6). This pathway generates long-chain SFA, mainly palmitate (16 0). The de novo synthesized palmitate and the palmitate derived from dietary sources are transported to the ER membranes. In the membranes, two major fatty acid enzymatic modifications of chain elongation and desaturation occur to yield longer chain SFA and unsaturated fatty acids of the n - 9 series. The n - 3 and n - 6 series of PUFA can be synthesized only from dietary fats, as animal cells do not have the... 

Fig. 33.1. Lipogenesis, the synthesis of triacylglycerols from glucose. In humans, the synthesis of fatty acids from glucose occurs mainly in the liver. Fatty acids (FA) are converted to triacylglycerols (TG), packaged in VLDL, and secreted into the blood. OAA = oxaloacetate.

C. Synthesis of Fatty Acids from Glucose and Other Substrates. 158... 

Several of the B vitamins are essential for normal fatty-acid metabolism (Table 2). Pantothenic acid is a constituent of CoA and is thus required for numerous reactions of fatty acids. Niacin and riboflavin are necessary for the synthesis of oxidized and reduced NAD(P) and FAD, respectively. These compounds play essential roles in fatty-acid oxidation, synthesis, and elongation. Biotin is a constituent of acetyl-CoA carboxylase and pyruvate carboxylase, both of which are involved in the synthesis of fatty acids from glucose. Thiamine is required for activity of the pyruvate dehydrogenase complex, which also participates in fatty-acid synthesis from glucose. 

Metabolism—increased use of glucose (sugar) and liberation of fatty acids from adipose tissue... 

Changes in the blood levels of these hormones all contribute to regulation of blood glncose level in several conditions. After a meal glucose utilisation is increased, since insulin stimulates glucose uptake by muscle and inhibits release of fatty acids from adipose tissue. Physical activity... 

A variety of fuels are available to generate ATP for muscle activity phosphocreatine glycogen (which can be converted to lactic acid or completely oxidised to CO2) glucose (from liver glycogen, transported to the muscle via the blood and completely oxidised to CO2) triacylglycerol within the muscle (completely oxidised to CO2) and fatty acids from triacylglycerol in adipose tissue (completely oxidised to CO2). 

Glycogen conversion to Blood glucose Blood fatty acids (from adipose tissue triacylglycerol)... 

Because digestion of food in the intestinal tract is dispensable and only counterproductive, the propulsion of intestinal contents is slowed to the extent that peristalsis diminishes and sphinc-teric tonus increases. However, in order to increase nutrient supply to heart and musculature, glucose from the liver and free fatty acid from adipose tissue must be released into the blood. The bronchi are dilated, enabling tidal volume and alveolar oxygen uptake to be increased. 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

A reduction of HED uptake in patients with moderate heart failure is a predictor of poor outcome, a finding consistent with SPECT MIBG studies [137]. HED PET imaging demonstrates reinnervation of the transplanted heart [138] paralleling recovery of primarily fatty acids metabolism after an initial metabolic shift from fatty acids to glucose utilization associated with myocardial denervation [139]. 

Animals cannot convert acetyl-CoA derived from fatty acids into glucose plants and microorganisms can. 

Malonyl-CoA, the first intermediate in the cytosolic biosynthesis of long-chain fatty acids from acetyl-CoA (see Fig. 21-1), increases in concentration whenever the animal is well supplied with carbohydrate excess glucose that cannot be oxidized or stored as glycogen is converted in the cytosol into fatty acids for storage as triacylglycerol. The inhibition of carnitine acyltrans-ferase I by malonyl-CoA ensures that the oxidation of... 

T Biosynthesis and degradation of triacylglycerols are regulated such that the favored path depends on the metabolic resources and requirements of the moment. The rate of triacylglycerol biosynthesis is profoundly altered by the action of several hormones. Insulin, for example, promotes the conversion of carbohydrate to triacylglycerols (Fig. 21-19). People with severe diabetes mellitus, due to failure of insulin secretion or action, not only are unable to use glucose properly but also fail to synthesize fatty acids from... 

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