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LIPID METABOLISM SUMMARY

How Are Lipids Involved in the Generation and Storage of Energy? We have already seen how carbohydrates are processed catabolically and anabolically. Lipids are another class of nutrient. The catabolic oxidation of lipids releases large quantities of energy, whereas the anabolic formation of lipids represents an efficient way of storing chemical energy. How Are Lipids Catabolized? The oxidation of fatty acids is the chief source of energy in the catabolism of lipids. After an initial activation step in the cytosol, the breakdown of fatty acids takes place in the mitochondrial matrix by the process of -oxidation. In this process, two-carbon units are successively removed from the carboxyl end of the fatty acid to produce acetyl-CoA, which subsequently enters the citric acid cycle. The reactions that liberate the acetyl-CoA units from a fatty acid produce NADH and FADH2, which eventually produce ATP via the electron transport chain. What Is the Energy Yield from the Oxidation of Fatty Acids? There is a net yield of 120 ATP molecules for each molecule of stearic acid (an 18-carbon compound) that is completely oxidized to carbon dioxide and water. The source of these ATP molecules is the production of NADH and FADH2 in the -oxidation pathway, as well as the NADH, FADH2, and GTP produced when the acetyl-CoA molecules are processed through the electron transport chain. How Are Unsaturated Fatty Acids and Odd-Carbon Fatty Acids Catabolized? The pathway of catabolism of fatty acids includes reactions in which unsaturated, as well as saturated, fatty acids can be metabolized. Odd-numbered fatty acids can also be metabolized by converting their unique breakdown product, propionyl-CoA, to succinyl-CoA, an intermediate of the citric acid cycle. What Are Ketone Bodies? Ketone bodies are substances related to acetone that are produced when an excess of acetyl-CoA results from -oxidation. This situation can arise from a large intake of lipids and a low intake of carbohydrates or can occur in diabetes, in which the inability to metabolize carbohydrates causes an imbalance in the breakdown products of carbohydrates and lipids. How Are Fatty Acids Produced? The anabolism of fatty acids proceeds by a different pathway from -oxidation. Some of the most important differences between the two processes are the requirement for biotin in anabolism, but not in catabolism, and the requirement for NADPH in anabolism, rather than the NAD+ required in catabolism. Fatty-acid biosynthesis occurs in the cytosol, catalyzed by an ordered multienzyme complex; fatty-acid catabolism occurs in the mitochondrial matrix, with no ordered aggregate of enzymes.

AMINO ACID METABOLISM

How Are Amino Acids Synthesized? In the anabolism of amino acids, transamination reactions play an important role. Glutamate and glutamine are frequently the amino-group donors. The enzymes that catalyze transamination reactions frequently require pyridoxal phosphate as a coenzyme. One-carbon transfers also operate in the anabolism of amino acids. Carriers are required for the one-carbon groups transferred. Tetrahydrofolate is a carrier of methylene and formyl groups, and S-adenosylmethionine is a carrier of methyl groups. What Are the Essential Amino Acids? Some species, including humans, cannot synthesize all the amino acids required for protein synthesis and must therefore obtain these essential amino acids from dietary sources. About half of the standard 20 amino acids are essential in humans, including arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. How Are Amino Acids Catabolized? The catabolism of amino acids has two parts: the fate of the nitrogen and the fate of the carbon skeleton. In the urea cycle, nitrogen released by the catabolism of amino acids is converted to urea. The carbon skeleton is converted to pyruvate or oxaloacetate, in the case of glucogenic amino acids, or to acetyl-CoA or acetoacetyl-CoA, in the case of ketogenic amino acids. How Are Purines Synthesized? The anabolic pathway of nucleotide synthesis involving purines differs from that involving pyrimidines. Both pathways use preformed ribose-5-phosphate but differ with regard to the point in the pathway at which the sugar phosphate is attached to the base. In the case of purine nucleotides, the growing base is attached to the sugar phosphate during the synthesis. How Are Purines Catabolized? In catabolism, purine bases are frequently salvaged and reattached to sugar phosphates. Otherwise, purines are broken down to uric acid. How Are Pyrimidines Synthesized and Catabolized? In pyrimidine biosynthesis, the base is first formed and then attached to the sugar phosphate. Pyrimidines are degraded to -alanine. How Are Ribonucleotides Converted to Deoxyribonucleotides? Deoxyribonucleotides for DNA synthesis are produced by the reduction of ribonucleoside diphosphates to deoxyribonucleoside diphosphates. How Is dUTP Converted to dTTP? Another reaction specifically needed to produce substrates for DNA synthesis is the conversion of uracil to thymine. This

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pathway, which requires a tetrahydrofolate derivative as the carrier for onecarbon transfer, is a target for cancer chemotherapy.

COORDINATION OF METABOLISM
How Are the Metabolic Pathways Connected? All metabolic pathways are related, and some metabolites appear in several pathways. Furthermore, many reactions of metabolism can take place simultaneously. The citric acid cycle plays a central role in metabolism, in both catabolic and anabolic pathways. The breakdown products of sugars, fatty acids, and amino acids all enter the citric acid cycle. How Can Biochemistry Help Us Understand Nutrition? The sources of substrates for catabolism and for anabolism are the nutrients derived from foodstuffs. In humans, the choice of diet becomes important in the interest of obtaining enough of essential nutrients while avoiding excesses of others, such as saturated fats, where excess is known to play a role in the development of health problems. In 1992, a food guide pyramid was published to explain nutrition basics to the public. This pyramid is currently being replaced by a newer version that recognizes the differences between various types of fats and carbohydrates instead of just sending the message that all fats are bad and all carbohydrates are good. What Are Hormones and Second Messengers? Sophisticated fine tuning of metabolic processes in multicellular organisms is possible through the actions of hormones and second messengers. In humans, a complex hormonal system has evolved that requires releasing factors (under the control of the hypothalamus), trophic hormones (under the control of the pituitary), and specific hormones for target organs (under the control of endocrine glands). Feedback control occurs at every level of the system. How Are Hormones Involved in the Control of Metabolism? When a hormone binds to its receptor on the plasma membrane of a target cell, it sets off a cascade of reactions by which second messengers elicit the actual cellular response. Two of the most important second messengers, cyclic AMP (cAMP) and phosphatidylinositol-4,5-bisphosphate (PIP2), activate protein kinases. Calcium ion is intimately involved in the action of PIP2. Hormonal triggering can be added to other levels of control of metabolism, such as allosteric activation and covalent modification, to ensure an efficient response to the needs of the organism. What Are the Many Effects of Insulin? Insulins primary job is to stimulate the glucose transporters in muscleparticularly the GLUT4 transporterto take up

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glucose from the blood. In addition, it has a wide range of intracellular effects, such as switching off glycogen breakdown and turning on glycogen synthesis, stimulating glycolysis in the liver and muscle, turning off gluconeogenesis in the liver, and stimulating fatty-acid synthesis and storage. A recent discovery is that elevated levels of insulin in the blood may be related to Alzheimers disease.