Metabolic relationships Seminar No. 5 - Chapter 16 - Transformation of energy in human body Basal metabolism depends on * sex (in females by cca 10 % lower) * age (diminishes with age) * body temperature (increase by 1 °C increases BM by 12 %) * hormones thyroxine, adrenalin - increase BM * long-term starvation -- BM goes down (lowering diets, anorexia nervosa) BM estimation (see p. 90) Energy expenditure in various conditions (MJ/day) BM - anorexia nervosa BM - lowering diets BM - females BM - males Light work Medium hard work Hard work 1-2 4-5 6-7 7-8 8-11 11-14 14-18 Main sources of nutrients Energy content in nutrients Recommended intake of nutrients Energy reserves in adult man (70 kg) Q. 1 (p. 95) What is the performance of an active student in seminar if his body surface is 1.73 m^2 ? Express it in Watts. Use the data from the chart on p. 90. A. 1 Energy expenditure of a student = basal expenditure (= BM) + activity in seminar = 4.2 × 1.73 + 4 = 11.266 MJ/day = 11 266 000 J/day = (J/s) = 130 J/s = 130 W Q.2 (p. 95) The rate of energy expenditure in a fasting man (70 kg) without physical activity is 7 MJ/d. How long do his energy stores last? A. 2 Energy stores: (data from table p. 90) 1.2 + 2.0 + 0.3 + 570.0 + 34.0 = 607.5 MJ BM = 7 MJ/d survival time = = 86.8 days Body mass index Basic facts on metabolism * ATP is immediate source of energy in cells * ATP is derived from metabolic oxidation of nutrients: glycolysis + b-oxidation of FA (r) acetyl-CoA (r) CAC (r) resp. chain (r) ATP * ATP and glucose levels in body have to be reasonably constant * glucose is necessary for brain and RBC * glucose is necessary for utilization of lipids for energy: Glc (r) pyruvate (r) oxalacetate (r) CAC * glucose cannot be made from FA Relationships between nutrients glucose (r) lipids ü FA (r) glucose glucogenic AA (r) glucose ü Glc (pyruvate, CAC intermed) (r) C skeleton of non-essential AA ü AA (r) lipids ü lipids (r) AA Saccharides in well-fed state (insulin) Glucose in liver (well fed state) * Glc (r) glycogen * Glc (r) pyruvate (r) acetyl-CoA (r) CAC (r) energy * Glc (r) pyruvate (r) acetyl-CoA (r) FA (r) TAG (VLDL) * considerable amount of Glc just passes through into blood * small portion of Glc is converted into specialized products (pentoses + NADPH, galactose, glucuronate) * excess of Glc (r) lipids (VLDL) (r) blood (r) adipose tissue (r) obesity Glc in other tissues (well fed state ) * Glc is the only fuel for RBC (anaerobic glycolysis) * Glc is prominent fuel for brain (aerobic glycolysis) * Glc is source of energy + reserves (glycogen) in muscles * Glc is source of glycerol-3-P for TAG synthesis in adipose tissues Lipids in well-fed state (insulin) Lipids in well-fed state (insulin) * Exogen. TAG (CM) and endogen. lipids (VLDL) supply peripheral tissues (muscles, myocard, kidney, adip. t.) * FA are released from TAG by the action of LPL * FA are fuel for muscles FA (r) acetyl-CoA (r) CAC (r) CO[2] + energy * In adipose tiss., FA are substrates for TAG synthesis Q. Which extrahepatal tissues utilize glucose in well-fed state? What is the role of insulin in this process? A. * most tissues: * RBC + brain (exclusively in well-fed state) * muscles + adipose tissue + some other ... * insulin stimulates the exposition of GLUT4 in muscles and adip. tiss. cell membranes * Glc can enter these organs Q. Why is glucose needed for adipose tissue? A. * Glc is the source of energy (aerobic glycolysis) * Glc is the source of NADPH +H^+ for FA synthesis (pentose cycle) * Glc is the source of glycerol-3-P for TAG synthesis glycerol-3-P (r) 1-acylglycerol-3-P (r) 1,2-diacylglycerol-3-P (r) 1,2-diacylglycerol (r) TAG Q. How can FA be formed from glucose? A. * Glc (r) 2 pyruvate (aerobic glycolysis) * pyruvate (r) acetyl-CoA (oxidative decarboxylation) * acetyl-CoA + CO[2] (biotin) (r) malonyl-CoA (activation) * [malonyl-CoA + acetyl-CoA][nx] (r) (r) FA Q. (p. 91) Why are KB not formed during resorption state? A. * there is not enough substrate for KB synthesis * insulin has anti-lipolytic action TH not enough FA and acetyl-CoA Saccharides in fasting (glucagon) Glucose in fasting (glucagon) * blood Glc level is maintained by two processes: * (1) liver glycogenolysis (Glc)[n] + P[i] (r) (Glc)[n-1] + Glc-1-P Glc-6-P (r) Glc * (2) liver gluconeogenesis from lactate, AA, glycerol * in muscles + brain, glycolysis is partly anaerobic Glc (6C) (r) 2 lactate (3C) * the body starts to save glucose Substrates of gluconeogenesis Lactate(60 %) Alanine + other glucogennic AA (30 %) Glycerol (10 %) Lipids in fasting (glucagon) Lipids in fasting (glucagon) * glucagon stimulates lipolysis in adip. tiss. (HSL) TAG (r) 3 FA + glycerol * FA are released to blood, bound to albumin, and trasferred to muscles ((r) CO[2] + energy) to liver ((r) partly CO[2] + energy for liver, partly KB for export) * KB are metabolic fuel for muscles and partly for brain Ketone bodies Ketone bodies as the source of energy Q. In which tissue are KB produced? Which substrate is the source? What is the cause of increased synthesis of KB? A. * KB are produced only in liver from acetyl-CoA * liver is not able to utilize KB * the metabolic cause: the shortage of oxaloacetate and excess of acetyl-CoA Q. * How does lipoprotein lipase act on fat reserves in body? * How does hormon sensitive lipase act on fat reserves in body? A. Metabolic turn-over of saccharides in fasting (g/d) Metabolic turn-over of lipids in fasting (g/d) Adaptation to prolonged starvation * muscle proteolysis: 75 (r) 20 g/d TH decreases * liver gluconeogenesis: 180 (r) 80 g/d TH decreases * lipolysis: 160 (r) 150 g/d TH approx. the same * KB production: 60 (r) 57 g/d TH approx. the same (dif. utiliz.) * energy for brain: Glc (44 g/d) + KB (47 g/d) * energy for muscle: FA Q. Which are the main priorities of metabolism during long starvation? A. * sparing glucose * sparing proteins Q. How does a long term fasting affect the acid-base balance? A. * the accumulation of acetoacetate and b-hydroxybutyrate in ECF leads to the decresase of pH TH acidosis