Metabolism refers to the physical and chemical processes that occur inside the cells of the body and that maintain life. Metabolism consists of anabolism (the constructive phase) and catabolism (the destructive phase, in which complex materials are broken down). The transformation of the macronutrients, carbohydrates, fats, and proteins in food to energy, and other physiological processes are parts of the metabolic process. ATP (adinosene triphosphate) is the major form of energy used for cellular metabolism.
Carbohydrates made up of carbon, hydrogen, and oxygen atoms are classified as mono-, di-, and poly-saccharides, depending on the number of sugar units they contain. The monosaccharides—glucose, galactose, and fructose—obtained from the digestion of food are transported from the intestinal mucosa via the portal vein to the liver. They may be utilized directly for energy by all tissues; temporarily stored as glycogen in the liver or in muscle; or converted to fat, amino acids, and other biological compounds.
Carbohydrate metabolism plays an important role in both types of diabetes mellitus. The entry of glucose into most tissues—including heart, muscle, and adipose tissue—is dependent upon the presence of the hormone insulin. Insulin controls the uptake and metabolism of glucose in these cells and plays a major role in regulating the blood glucose concentration. The reactions of carbohydrate metabolism cannot take place without the presence of the B vitamins, which function as coenzymes. Phosphorous, magnesium, iron, copper, manganese, zinc, and chromium are also necessary as cofactors.
Carbohydrate metabolism begins with glycolysis, which releases energy from glucose or glycogen to form two molecules of pyruvate, which enter the Krebs cycle (or citric acid cycle), an oxygen-requiring process, through which they are completely oxidized. Before the Krebs cycle can begin, pyruvate loses a carbon dioxide group to form acetyl coenzyme A (acetyl-CoA). This reaction is irreversible and has important metabolic consequences. The conversion of pyruvate to acetyl-CoA requires the B vitamins.
The hydrogen in carbohydrate is carried to the electron transport chain, where the energy is conserved in ATP molecules. Metabolism of one molecule of glucose yields thirty-one molecules of ATP. The energy released from ATP through hydrolysis (a chemical reaction with water) can then be used for biological work.
Only a few cells, such as liver and kidney cells, can produce their own glucose from amino acids, and only liver and muscle cells store glucose in the form of glycogen. Other body cells must obtain glucose from the bloodstream.
Glycogenesis is the conversion of excess glucose to glycogen. Glycogenolysis is the conversion of glycogen to glucose (which could occur several hours after a meal or overnight) in the liver or, in the absence of glucose-6-phosphate in the muscle, to lactate. Gluco-neogenesis is the formation of glucose from noncarbo-hydrate sources, such as certain amino acids and the glycerol fraction of fats when carbohydrate intake is limited. Liver is the main site for gluconeogenesis, except during starvation, when the kidney becomes important in the process. Disorders of carbohydrate metabolism include diabetes mellitus, lactose intolerance, and galactosemia.
Proteins contain carbon, hydrogen, oxygen, nitrogen, and sometimes other atoms. They form the cellular structural elements, are biochemical catalysts, and are important regulators of gene expression. Nitrogen is essential to the formation of twenty different amino acids, the building blocks of all body cells. Amino acids are characterized by the presence of a terminal carboxyl group and an amino group in the alpha position, and they are connected by peptide bonds.
Digestion breaks protein down to amino acids. If amino acids are in excess of the body’s biological requirements, they are metabolized to glycogen or fat and subsequently used for energy metabolism. If amino acids are to be used for energy their carbon skeletons are converted to acetyl CoA, which enters the Krebs cycle for oxidation, producing ATP. The final products of protein catabolism include carbon dioxide, water, ATP, urea, and ammonia.
Vitamin B6 is involved in the metabolism (especially catabolism) of amino acids, as a cofactor in transamination reactions that transfer the nitrogen from one keto acid (an acid containing a keto group ‘-CO-’ in addition to the acid group) to another. This is the last step in the synthesis of nonessential amino acids and the first step in amino acid catabolism. Transamination converts amino acids to L-glutamate, which undergoes oxidative deamination to form ammonia, used for the synthesis of urea. Urea is transferred through the blood to the kidneys and excreted in the urine.
The glucose-alanine cycle is the main pathway by which amino groups from muscle amino acids are transported to the liver for conversion to glucose. The liver is the main site of catabolism for all essential amino acids, except the branched-chain amino acids, which are catabolized mainly by muscle and the kidneys. Plasma amino-acid levels are affected by dietary carbohydrate through the action of insulin, which lowers plasma amino-acid levels (particularly the branched-chain amino acids) by promoting their entry into the muscle.
Body proteins are broken down when dietary supply of energy is inadequate during illness or prolonged starvation. The proteins in the liver are utilized in preference to those of other tissues such as the brain. The gluconeogenesis pathway is present only in liver cells and in certain kidney cells.
Disorders of amino acid metabolism include phe-nylketonuria, albinism, alkaptonuria, type 1 tyrosi-naemia, nonketotic hyperglycinaemia, histidinaemia, homocystinuria, and maple syrup urine disease.
Fat (Lipid) Metabolism
Fats contain mostly carbon and hydrogen, some oxygen, and sometimes other atoms. The three main forms of fat found in food are glycerides (principally triacylglycerol ‘triglyceride’, the form in which fat is stored for fuel), the phospholipids, and the sterols (principally cholesterol). Fats provide 9 kilocalories per gram (kcal/g), compared with 4 kcal/g for carbohydrate and protein. Triacylglycerol, whether in the form of chylomicrons (microscopic lipid particles) or other lipoproteins, is not taken up directly by any tissue, but must be hydrolyzed outside the cell to fatty acids and glycerol, which can then enter the cell.
Fatty acids come from the diet, adipocytes (fat cells), carbohydrate, and some amino acids. After digestion, most of the fats are carried in the blood as chylomicrons. The main pathways of lipid metabolism are lipolysis, betaoxidation, ketosis, and lipogenesis.
Lipolysis (fat breakdown) and beta-oxidation occurs in the mitochondria. It is a cyclical process in which two carbons are removed from the fatty acid per cycle in the form of acetyl CoA, which proceeds through the Krebs cycle to produce ATP, CO2, and water.
Ketosis occurs when the rate of formation of ketones by the liver is greater than the ability of tissues to oxidize them. It occurs during prolonged starvation and when large amounts of fat are eaten in the absence of carbohydrate.
Cholesterol is either obtained from the diet or synthesized in a variety of tissues, including the liver, adrenal cortex, skin, intestine, testes, and aorta. High dietary cholesterol suppresses synthesis in the liver but not in other tissues.
Carbohydrate is converted to triglyceride utilizing glycerol phosphate and acetyl CoA obtained from glycolysis. Ketogenic amino acids, which are metabolized to acetyl CoA, may be used for synthesis of triglycerides. The fatty acids cannot fully prevent protein breakdown, because only the glycerol portion of the triglycerides can contribute to gluconeogenesis. Glycerol is only 5% of the triglyceride carbon.
Most of the major tissues (e.g., muscle, liver, kidney) are able to convert glucose, fatty acids, and amino acids to acetyl-CoA. However, brain and nervous tissue—in the fed state and in the early stages of starvation—depend almost exclusively on glucose. Not all tissues obtain the major part of their ATP requirements from the Krebs cycle. Red blood cells, tissues of the eye, and the kidney medulla gain most of their energy from the anaerobic conversion of glucose to lactate.