11
Metabolism, the Stress Response to Surgery and Perioperative Thermoregulation
METABOLISM
Adenosine triphosphate (ATP) is the ‘energy currency’ of the body. It contains two high-energy phosphate bonds and is present in all cells. Most physiological processes acquire energy from it. Oxidation of nutrients in cells releases energy, which is used to regenerate ATP. Conversion of one mole of ATP to adenosine diphosphate (ADP) releases 8 kcal of energy. Additional hydrolysis of the phosphate bond from ADP to AMP also releases 8 kcal (Fig. 11.1). Other high-energy compounds include creatine phosphate and acetyl CoA. The generation of energy through the oxidation of carbohydrate, protein and fat is termed catabolism, whereas the generation of stored energy as energy-rich phosphate bonds, carbohydrates, proteins or fats is termed anabolism (Fig. 11.2). The amount of energy released by carbohydrate, protein and fat metabolism is: carbohydrate 4.1 kcal g–1, protein 4.1 kcal g–1 and fat 9.3 kcal g–1.
FIGURE 11.1 Hydrolysis of adenosine triphosphate (ATP). ADP, adenosine diphosphate; AMP, adenosine monophosphate.
CARBOHYDRATE METABOLISM
Aerobic Glycolysis
The mechanism of glucose catabolism involves an extensive series of enzyme-controlled steps, rather than a single reaction. This is because the oxidation of one mol of glucose (180 g) releases almost 686 kcal of energy, whereas only 8 kcal is required to form one molecule of ATP. Therefore, an elaborate series of reactions, termed the glycolytic pathway, releases small quantities of energy at a time, resulting in the synthesis of 38 mol of ATP from each mol of glucose (Fig. 11.3). As each molecule of ATP releases 8 kcal, a total of 304 kcal of energy in the form of ATP is synthesized. Hence, the efficiency of the glycolytic pathway is 44%, the remainder of the energy being released as heat.
FIGURE 11.3 Summary of the glycolytic pathway. Krebs citric acid cycle. FFA, free fatty acid. Note that two molecules of pyruvic acid are produced for each molecule of glucose metabolized. Each pyruvic acid molecule enters the Krebs citric acid cycle.
The glycolytic pathway may be summarized as:
1. Glycolysis, i.e. splitting the glucose (6 carbon atoms) molecule into two molecules of pyruvic acid (3 carbon atoms each). This results in the net formation of two molecules of ATP anaerobically but also generates two pairs of H+ for entry into the respiratory chain (see below) (Fig. 11.4).
2. Oxidation of each of the pyruvic acid (3 carbon atom) molecules in the Krebs citric acid cycle results in the generation of five pairs of H+ per 3-carbon moiety, i.e. 10 pairs of H+ per 6 carbon glucose molecule (Fig. 11.5).
FIGURE 11.5 The Krebs citric acid cycle. Note that five pairs of H+ are generated by the oxidation of each pyruvate molecule. Each pair of H+ generates three molecules of ATP in the respiratory chain in the mitochondria.
3. Oxidative phosphorylation, i.e. the formation of ATP by the oxidation of hydrogen to water. This process is also known as the respiratory chain. For each molecule of glucose, a total of 12 pairs of H+ are fed into the respiratory chain, each pair generating three molecules of ATP. Thus, oxidative phosphorylation results in 36 molecules of ATP per molecule of glucose. A further two molecules of ATP are produced anaerobically. Therefore, one molecule of glucose generates 38 molecules of ATP. Uncoupling of oxidative phosphorylation allows ATP production to be sacrificed for heat production as part of thermoregulatory homeostasis.
PROTEIN METABOLISM
There is equilibrium between the amino acids in plasma, plasma proteins and tissue proteins. Proteins may be synthesized from amino acids in all cells of the body, the type of protein depending on the genetic material in the DNA, which determines the sequence of amino acids formed and hence controls the nature of the synthesized proteins. Essential amino acids must be ingested as they cannot be synthesized in the body. Table 11.1 lists the eight essential amino acids. If there is dietary deficiency of any of these, the subject develops a negative nitrogen balance. Others are non-essential (i.e. may be synthesized in the cells). Synthesis is by the process of transamination, whereby an amine radical (-NH2) is transferred to the corresponding α-keto acid. Breakdown of excess amino acids into glucose (gluconeogenesis) generates energy or storage as fat, both of which occur in the liver. The breakdown of amino acids occurs by the process of deamination, which takes place in the liver. It involves the removal of the amine group with the formation of the corresponding ketoacid. The amine radical may be recycled to other molecules or released as ammonia. In the liver, two molecules of ammonia are combined to form urea (Fig. 11.6). Amino acids may also take up ammonia to form the corresponding amide.
TABLE 11.1
Leucine
Isoleucine
Lysine
Methionine
Phenylalanine
Threonine
Tryptophan
Valine
FIGURE 11.6 Deamination is the process of metabolizing amino acids. Ammonia is the end product. Two molecules of ammonia combine as shown to form urea. This occurs in the liver.
LIPID METABOLISM
Lipids include triglycerides (TGs), phospholipids (PLs) and cholesterol. The basic structure of TGs and PLs is the fatty acid. Fatty acids are long-chain hydrocarbon organic acids. TGs are composed of three long-chain fatty acids bound with one molecule of glycerol (Fig. 11.7). Phospholipids have two long-chain fatty acids bound to glycerol with the third fatty acid replaced by attached compounds such as inositol, choline or ethanolamine. Although cholesterol does not contain fatty acid, its sterol nucleus is formed from fatty acid molecules.
very low-density lipoproteins (VLDLs), consisting mainly of TGs
low-density lipoproteins (LDLs), consisting mainly of cholesterol
high-density lipoproteins (HDLs), consisting mainly of protein.
Cholesterol
The serum cholesterol concentration is correlated with the incidences of atherosclerosis and coronary artery disease. Prolonged elevations of VLDL, LDL and chylomicron remnants are associated with atherosclerosis. Conversely, HDL is protective. Factors affecting blood cholesterol concentration are outlined in Figure 11.8.
Ketones
Initial degradation of fatty acids occurs in the liver, but the acetyl-CoA may not be used either immediately or completely. Ketones, or keto acids, are either acetoacetic acid, formed from two molecules of acetyl CoA, β-hydroxybutyric acid, formed from the reduction of acetoacetic acid, or acetone, formed when a smaller quantity of acetoacetic acid is decarboxylated (Fig. 11.9