The metabolism of fats

The fatty acids are oxidized in the mitochondria by the -oxidation pathway, in which two carbon atoms at a time are removed from the fatty acid chain as acetyl CoA. This acetyl CoA then enters the citric acid cycle, together with that arising from the metabolism of pyruvate. 

1 Carnitine AND THE TRANSPORT OF FATTY ACIDS INTO THE MITOCHONDRION 

Acylcarnitine can cross only the inner mitochondrial membrane on a countertransport system that takes in acylcarnitine in exchange for free carnitine being returned to the inter-membrane space. Once inside the mitochondrial inner membrane, acylcarnitine transfers the acyl group onto CoA ready to undergo -oxidation. This counter-transport system provides regulation of the uptake of fatty acids into the mitochondrion for oxidation. As long as there is free CoA available in the mitochondrial matrix, fatty acids can be taken up and the carnitine returned to the outer membrane for uptake of more fatty acids. However, if most of the CoA in the mitochondrion is acylated, then there is no need for further fatty uptake immediately and, indeed, it is not possible. 

This carnitine shuttle also serves to prevent uptake into the mitochondrion (and hence oxidation) of fatty acids synthesized in the cytosol in the fed state malonyl 

CoA (the precursor for fatty acid synthesis section 5.6.1) is a potent inhibitor of carnitine palmitoyl transferase I in the outer mitochondrial membrane. 

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The 4-phosphopantetheine group of CoA is also utilized (for essentially the same purposes) in acyl carrier proteins (ACPs) involved in fatty acid biosynthesis (see Chapter 25). In acyl carrier proteins, the 4-phosphopantetheine is covalently linked to a serine hydroxyl group. Pantothenic acid is an essential factor for the metabolism of fat, protein, and carbohydrates in the tricarboxylic acid cycle and other pathways. In view of its universal importance in metabolism, it is surprising that pantothenic acid deficiencies are not a more serious problem in humans, but this vitamin is abundant in almost all foods, so that deficiencies are rarely observed. 

One of the steps in the metabolism of fats is the reaction of an unsaturated acyl CoA with water to give a /3-hydroxyacyl CoA. Propose a mechanism. 

The tiiyroid hormones influence every organ and tissue of tiie body. These hormones are principally concerned with increasing tiie metabolic rate of tissues, which results in increases in tiie heart and respiratory rate, body temperature, cardiac output, oxygen consumption, and the metabolism of fats, proteins, and carbohydrates. The exact mechanisms by which tiie tiiyroid hormones exert their influence 011 body organs and tissues are not well understood. 

In addition to these interconversions, the metabolism of fat and the metabolism of carbohydrate are inseparably related. This fact is most clearly demonstrated by the appearance of such abnormal products of fat oxidation as the so-called ketone bodies in the blood and urine whenever the supply of carbohydrate is deficient or in cases where the organism is unable to metabolize this foodstuff. Whether ketonuria results because the metabolism of fat must occur concomitantly with that of D-glucose (ketolysis), or whether the presence of D-glucose prevents any fat breakdown because it is preferentially oxidized (antiketogenesis) is still a moot question. 

Glucose is essential for the metabolism of fat and for providing ATP in red cells and brain. 

However, you get even more calories from the metabolism of fats and oils, a matter to which we turn our attention in the following two chapters. 

We are going to get back to matters of weight control and relate them to aspects of the metabolism of fats and oils. Before we can do that in a meaningful way, we need to say something about what fats and oils are. The key constituents of fats and oils are the fatty acids. So that is where we shall continue. 

These topics are discussed in Chapters 11, 14 and 22. Discussion in this chapter focuses primarily on the metabolism of fats that are fuels and that provide energy for various tissues under different conditions, many of which are common in everyday life. It also provides basic knowledge for the discussion in Chapters 11, 14 and 22. 

In developed conntries, fat provides about 40% of the total energy consnmed but in some individuals this percentage may be mnch higher. Almost all of this is in the form of triacylglycerol, containing mainly long-chain bnt also some short-chain fatty acids. The stractnre, digestion, absorption and eventual fate of the products of absorption are described in Chapters 4 and 5 and the metabolism of fat is discussed in Chapter 7. 

Spleen and Stomach, transform dampness and promote digestion, particularly the metabolism of fats. If hyperlipidemia has developed and has resulted in detectable damage to the heart, brain and vascular system, herbs to strongly remove dampness and phlegm, clear heat, stimulate Qi movement and blood circulation, nourish the Yin and pacify the Liver should be added to the formula. In all conditions, herbs that tonify the Spleen and Kidney should be prescribed. 

In selecting carbohydrate metabolism to illustrate the principles of metabolic regulation, we have artificially separated the metabolism of fats and carbohydrates. In fact, these two activities are very tightly integrated, as we shall see in Chapter 23. 

As complex as the regulation of carbohydrate metabolism is, it is far from the whole story of fuel metabolism. The metabolism of fats and fatty acids is very closely tied to that of carbohydrates. Hormonal signals such as insulin and changes in diet or exercise are equally important in regulating fat metabolism and integrating it with that of carbohydrates. We shall return to this overall metabolic integration in mammals in Chapter 23,... 

Pharmaceuticals. Lecithin and especially purified phosphatidylcholine can act as excipients in pharmaceutical (drug) formulation to enhance and control the Unavailability of the active component. Moreover, phosphatidylcholine can be utilized as a diedelic source, as it involved in the cholesterol metabolism and the metabolism of fats in the liver also, it can be utilized as a precursor of brain acetylcholine, as neurotransmiticr. 

Vitamins are minor components of foods that play an essential role in human nutrition. Many vitamins are unstable under certain conditions of processing and storage (Table 9-1), and their levels in processed foods, therefore, may be considerably reduced. Synthetic vitamins are used extensively to compensate for these losses and to restore vitamin levels in foods. The vitamins are usually divided into two main groups, the water-soluble and the fat-soluble vitamins. The occurrence of the vitamins in the various food groups is related to their water-or fat-solubility. The relative importance of certain types of foods in supplying some of the important vitamins is shown in Table 9-2. Some vitamins function as part of a coenzyme, without which the enzyme would be ineffective as a biocatalyst. Frequently, such coenzymes are phosphorylated forms of vitamins and play a role in the metabolism of fats, proteins, and carbohydrates. Some vitamins occur in foods as provitamins—compounds that are not vitamins but can be changed by the body into vitamins. Vitamers are members of the same vitamin family. 

Most aspects t>f carbohydrate nutrition are simpler than those of other nutrients, (For example, fat nutrition is complicated by the fact that the metabolism of fats requires bile salts to maintain solubility during digestion and lipoproteins and albumin during distribution in the body.) On the other hand, the nutrition of the carbohydrates that take the form of dietary fibers is very complicated. This complexity . > due to the fact that they arc metabolized by enzymes of the gut microflora. 

Pantothenic acid is a component of coenzyme A (CoA) and is required for the metabolism of fat, protein, and carbohydrate via the citric acid cycle. 

Biotin, sometimes called vitamin H, is involved in carboxylation and decarboxylation reactions in the metabolism of fats, carbohydrates, and proteins. Liver, egg yolks, cheese, and peanuts are excellent sources of biotin. In addition, it is produced by bacteria in the intestine. 

The sequence of events known as the Krebs cycle is indeed a cycle ox-aloacetate is both the first reactant and the final product of the metabolic pathway (creating a loop). Because the Krebs cycle is responsible for the ultimate oxidation of metabolic intermediates produced during the metabolism of fats, proteins, and carbohydrates, it is the central mechanism for metabolism in the cell. In the first reaction of the cycle, acetyl CoA condenses with oxaloacetate to form citric acid. Acetyl CoA utilized in this way by the cycle has been produced either via the oxidation of fatty acids, the breakdown of certain amino acids, or the oxidative decarboxylation of pyruvate (a product of glycolysis). The citric acid produced by the condensation of acetyl CoA and oxaloacetate is a tricarboxylic acid containing three car-boxylate groups. (Hence, the Krebs cycle is also referred to as the citric acid cycle or tricarboxyfic acid cycle.)... 

Not only are the technical aspects of sample taking important, but so also is the timing of this operation in order to maximize the usefulness of the analytical results, and, in fact, strict rules (e.g. use of the fasting value) for analyses performed in the course of investigations into the metabolism of fats and carbohydrates have been routinely followed for many years. 

In the oxidation of fats, the classical )8-oxidation to acetyl-coenzyme A occurs in the mitochondria of all kinds of cells. Some cells have one or two subsidiary mechanisms as well. Because the metabolism of fat produces twice as much water as that of either carbohydrate or protein, cells which have to encounter sudden dehydrating conditions usually have a high fat metabolism. Parasitic nematode worms are a striking example of this (Baldwin, 1948b). 

Riboflavin, also known as vitamin B2, is the central component of FAD and FMN, and is therefore required by all flavo proteins. It plays an important role in the metabolism of fats, ketone bodies, carbohydrates, and proteins. Riboflavin for industrial use is mainly produced from ascomycete fungi in aerobic fermentation. Three quarters of riboflavin is used as a feed additive and the remaining is used as food additives and in pharmaceuticals. Furthermore, FMN can be synthesized by chemical phosphorylation from riboflavin, while FAD can be produced by chemical synthesis or by microbial transformation, which uses FMN and ATP as the substrates. ... 

The metabolism of fat produces more water than either protein or carbohydrate... 

The close interrelationship that exists between the metabolism of fat and of carbohydrate is apparent in the production of ketone bodies and the abnormal metabolic condition of ketosis. liiis is associated with an increased oxidation of fat and decreased metabolism of carbohydrate. It occurs in starvation after the glycogen stores have been depleted, or when a diet rich in fat and low in carbohydrate is consumed. It also occurs in certain pathological conditions such as diabetes mellitus. 

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