Conversion of fat to carbohydrates

In addition to perfusion experiments, tests with tissue slices have been cited to prove the conversion of fat to carbohydrate. Here, both changes in composition of the slices and their R. Q. have been determined and certain deductions drawn from these values. When these slices are prepared from well-fed animals, the levels of R. Q. are usually from 0.75 to 0.85, which can hardly support the hypothesis that a conversion of fat to sugar is occurring. However, when the liver slices are obtained from rats in which the carbohydrate stores are depleted, either by fasting or by a previous high-fat diet, figures for the respiratory quotient below 0.70 have been reported - while Dickens and Simer found values below 0.70 only when the tests were carried out with phosphate or bi-... 

Kornberg, H. L. and Beevers, H. (1957) The glyoxylate cycle as a stage in the conversion of fat to carbohydrate in castor beans. Biochim. Biophys. Acta 26, 531-537. 

The possible conversion of fat to carbohydrate within the organism has been a subject of much controversy. While the glycerol component of the fat molecule can be transformed readily into liver glycogen, a carbohydrate precursor has not yet been identified among the products of fatty acid metabolism. The existence of a pituitary factor in carbohydrate metabolism has been established, and one of its effects is ascribed to promotion of glycogenesis from fatty acids. 

The first two stages of catabolism result in the conversion of fats and carbohydrates into acetyl groups that are bonded throi h a thiol ester link to coenzyme A. These acetyl groups now enter the third stage of catabolism— the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs. cycle. The steps of the citric acid cycle are given in Figure 29.6. ... 

The exact processes by which carbohydrates and fats are converted to CO2 and H2 O depend on the conditions and the particular needs of the cell. Each possible route involves a complex series of chemical reactions, many of which are accompanied by the conversion of ADP to ATP. One molecule of glucose, for example, is oxidized to CO2 and H2 O in a sequence of many individual reactions that can convert as many as 36 ADP molecules into ATP molecules H12 Og + 6 O2 + 36 ADP + 36 H3 PO4 6 CO2 + 36 ATP +42 H2 O... 

Although it ia becoming increasingly evident with each new discovery that the metabolism of no single foodstuff proceeds in a course entirely isolated from that of the other foodstuffs, the interrelationships are nowhere so apparent as they are between the utilization of carbohydrate and that of fat. The conversion of carbohydrate to fat is a phenomenon which has been repeatedly demonstrated experimentally the reverse change, namely, the conversion of natural fats to carbohydrate, is a disputed reaction and must certainly not occur except to a limited extent, if at all. 

It is clear from Equation (19.4) that saturated fat, not cholesterol, is the single most important factor that raises serum cholesterol. Some cases of hyperlipoproteinemia type IV (high VLDL) respond to low-carbohydrate diets, because the excess of VLDL comes from intestinal cells, where it is produced from dietary carbohydrate. Resins, such as cholestyramine and cholestipol, bind and cause the excretion of bile salts, forcing the organism to use more cholesterol. Lovastatin decreases endogenous cholesterol biosynthesis (see later), and niacin (nicotinic acid) apparently decreases the production of VLDL and, consequently, LDL. It also results in an HDL increase. Antioxidants that inhibit the conversion of LDL to oxidized LDL have also been used with some success. These are high doses of vitamin E and the drug probucol. 

Facilitates passage of glucose, K., Mg across cellular membranes of skeletal and cardiac muscle, adipose tissue controls storage and metabolism of carbohydrates, protein, fats. Promotes conversion of glucose to glycogen in liver. 

In animals TPP-dependent decarboxylation reactions are essential to the production of energy needed for cell metahohsm. In these reactions a-ketoacids are converted to acyl CoA molecules and carbon dioxide. The reactions (e.g., the conversion of pyruvate to acetyl CoA) are an important part of the breakdown of carbohydrates, and of the conversion of several classes of molecules (carbohydrates, fats, and proteins) to energy, carbon dioxide, and water in the citric acid cycle. In other organisms, in addition to its participation in the above reactions, TPP is a required coenzyme in alcohol fermentation, in the carbon fixation reactions of photosynthesis, and in the hiosynthesis of the amino acids leucine and valine. 

This reaction, which produces oxaloacetate from pyruvate, provides a connection between the amphibolic citric acid cycle and the anabolism of sugars by gluconeogenesis. On this same topic of carbohydrate anabolism, we should note again that pyruvate cannot be produced from acetyl-GoA in mammals. Because acetyl-GoA is the end product of catabolism of latty acids, we can see that mammals could not exist with fats or acetate as the sole carbon source. The intermediates of carbohydrate metabolism would soon be depleted. Garbohydrates are the principal energy and carbon source in animals (Figure 19.11), and glucose is especially critical in humans because it is the preferred fuel for our brain cells. Plants can carry out the conversion of acetyl-GoA to pyruvate and oxaloacetate, so they can exist without carbohydrates as a carbon source. The conversion of pyruvate to acetyl-GoA does take place in both plants and animals (see Section 19.3). 

Hikasa et al. (76) interpreted the results of these studies as indicating that cholesterol stone formation in hamsters is related to a relative deficiency in the supply of linoleic acid or its conversion to arachidonic acid and other unsaturated derivatives by pathways dependent on pyridoxal phosphate. Nonabsorbable carbohydrates were thought to favor growth of elements of the bacterial flora that produce vitamin Be and thus prevent stone formation. Diets high in saturated and short-chain fats, and low in linoleic acid, may also inhibit conversion of pyrisoxine to pyrisoxal phosphate and so favor stone... 

The human body can convert glucose to fatty acids, but it cannot convert fatty acids to glucose. Our cells contain no enzyme that can catalyze the conversion of acetyl CoA to pyruvate, a compound required for gluconeogenesis (Figure 13.13). However, plants and some bacteria do possess such enzymes and convert fats to carbohydrates as part of their normal metabolism. 

The fats are essential constituents of the food of animals, although conversion of carbohydrates to fats in the animal body does occur. They are partially absorbed from the gut as fats to the lymphatic system and par-... 

Physiological Role of Citric Acid. Citric acid occurs ia the terminal oxidative metabolic system of virtually all organisms. This oxidative metabohc system (Fig. 2), variously called the Krebs cycle (for its discoverer, H. A. Krebs), the tricarboxyUc acid cycle, or the citric acid cycle, is a metaboHc cycle involving the conversion of carbohydrates, fats, or proteins to carbon dioxide and water. This cycle releases energy necessary for an organism s growth, movement, luminescence, chemosynthesis, and reproduction. The cycle also provides the carbon-containing materials from which cells synthesize amino acids and fats. Many yeasts, molds, and bacteria conduct the citric acid cycle, and can be selected for thek abiUty to maximize citric acid production in the process. This is the basis for the efficient commercial fermentation processes used today to produce citric acid. 

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