Chapter 22a Metabolism and Energy Balance About this Chapter • • • • • Appetite and satiety Energy balance Metabolism Homeostatic control of metabolism Regulation of body temperature Appetite and Satiety • Food intake is carefully controlled • Two competing behavioral states • Appetite (or hunger) = desire for food • Satiety = sense of fullness (or satisfaction) • Hypothalamus contains two key control centers • Feeding center • Satiety center Four Types of Input to the Hypothalamus • • • • Neural input from the cerebral cortex Neural input from the limbic system Peptide hormones from the GI tract Adipocytokines from adipose tissue Two Theories for Regulation of Food Intake • Glucostatic theory • Theory proposes that blood glucose levels ultimately control the feeding and satiety centers • Lipostatic theory • Theory proposes that the level of body fat regulates the feeding and satiety centers • Recent discovery of several peptides (especially leptin and neuropeptide Y) seems to support this theory Peptides Regulate the Feeding Center Figure 22-1 Many Peptides Alter Food Intake Table 22-1 Energy Balance - The Key to Weight Control • Energy input = energy output • Energy output = work heat • Three categories of work done by our cells • Membrane transport • Mechanical work • Chemical work = building molecules, including synthesis of energy storage molecules • Short-term energy storage (ATP) • Long-term energy storage (glycogen, fat) Energy Balance • Methods for measuring energy use • Direct calorimetry • Measures the energy content of food • Fat 9 Kcal/g / protein and CHO ~ 4 Kcal/g • Indirect calorimetry • Estimates metabolic rate as a measure of energy use • Oxygen consumption • Carbon dioxide production • Ratio of CO2 to O2 (RQ or RER) Metabolic Rate • Basal metabolic rate (BMR) is most common measure of metabolic rate • Six factors affecting metabolic rate 1 - Age and gender 2 - Amount of lean muscle mass 3 - Activity level 4 - Energy intake (diet) – fat vs protein thermogenesis 5 – Hormones – thyroid hormone thyroxin 6 - Genetics • Only energy intake and level of physical activity can be voluntarily changed Two Chemical Forms of Energy Storage • Glycogen (highly branched polymer of glucose) • Stored glycogen binds water • Liver glycogen is used to regulate blood glucose • Muscle glycogen is used to power muscle contraction • Fat (triglycerides) • Fats have higher energy content per gram • Little water is required for fat storage • Energy in fats is harder and slower to access Metabolism • Metabolism is all of the chemical reactions in the body 1 - Extract energy from nutrients 2 - Use energy for work and synthesis 3 - Store excess energy • Two types of metabolic pathways • Anabolic pathways build large molecules • Catabolic pathways break down large molecules • Metabolism can be divided into two states • Absorptive (“fed”) state is anabolic • Post-absorptive (“fasted”) state is catabolic Metabolic Fates and Nutrient Pools • Ingested biomolecules have three fates 1. Immediate use in energy production 2. Synthesis into needed macromolecules 3. Storage for later use in energy production • Nutrient pools are available for immediate use • Free fatty acids • Plasma glucose pool • Amino acid pool Know definitions of: Glycogenesis / glycogenolysis / lipogenesis / lipolysis / ketosis Overview of Metabolism DIET Fats Carbohydrates Proteins Lipogenesis Free fatty acids + glycerol Fat stores Glucose Glycogenesis Lipogenesis Excess glucose Glycogen stores Lipolysis Excess nutrients Metabolism in most tissues Body protein Urine Glycogenolysis Glucose pool Free fatty acid pool Amino acids Protein synthesis Gluconeogenesis Range of normal plasma glucose Amino acid pool Brain metabolism Figure 22-2 Glucose Metabolism DIET Carbohydrates Fat stores Glucose Lipogenesis Excess glucose • Most plasma glucose is used for immediate energy production, or is Glycogenesis stored as glycogen Glycogen stores Urine Glycogenolysis Glucose pool Range of normal plasma glucose Metabolism in most tissues Brain metabolism Figure 22-2 (1 of 4) Fat Metabolism DIET Fats Lipogenesis Free fatty acids + glycerol Fat stores Lipolysis • Free fatty acids are used for immediate energy production, or are stored as fat molecules in adipose tissue Free fatty acid pool Excess nutrients Metabolism in most tissues Figure 22-2 (2 of 4) Amino Acid Metabolism DIET • Amino acids are used for building needed body proteins. Excess amino acids are converted into glucose by the liver. Proteins Amino acids Protein synthesis Body protein Glucose pool Gluconeogenesis Range of normal plasma glucose Amino acid pool Figure 22-2 (3 of 4) Summary of Metabolism DIET Fats Carbohydrates Proteins Lipogenesis Free fatty acids + glycerol Fat stores Glucose Glycogenesis Lipogenesis Excess glucose Glycogen stores Lipolysis Excess nutrients Metabolism in most tissues Body protein Urine Glycogenolysis Glucose pool Free fatty acid pool Amino acids Protein synthesis Gluconeogenesis Range of normal plasma glucose Amino acid pool Brain metabolism Figure 22-2 (4 of 4) Biochemical Pathways for Energy Production • Overview of Pathways Glycogen Glucose 6-phosphate Glucose Liver only Glycerol 2 ATP NH3 Some amino acids Lactate Pyruvate Cytoplasm Mitochondria Pyruvate Fatty acids Acetyl CoA CoA Ketone bodies (in liver) CO2 Citric acid cycle 2 Electron transport system NH3 O2 26-28 ATP ATP Some amino acids + H2O Figure 22-3 Interconversions of Glucose Glycogen Glucose 6-phosphate Glucose Liver only Cytoplasm Mitochondria Figure 22-3 (1 of 7) Glycolysis is Catabolism of Glucose Glycogen Glucose 6-phosphate Glucose Liver only 2 ATP Pyruvate Cytoplasm Mitochondria Figure 22-3 (2 of 7) Some Amino Acids Can Also Supply Pyruvate Glycogen Glucose 6-phosphate Glucose Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Cytoplasm Mitochondria Figure 22-3 (3 of 7) Anaerobic Metabolism Produces Lactate Glycogen Glucose 6-phosphate Glucose Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Lactate Cytoplasm Mitochondria Pyruvate Figure 22-3 (4 of 7) Mitochondria and the Citric Acid Cycle Glycogen Glucose 6-phosphate Glucose Liver only Glycerol 2 ATP NH3 Some amino acids Lactate Pyruvate Cytoplasm Mitochondria Pyruvate Acetyl CoA CoA CO2 Citric acid cycle 2 ATP Figure 22-3 (5 of 7) Fatty Acids and Some Amino Acids Enter Here Glycogen Glucose 6-phosphate Glucose Liver only Glycerol 2 ATP NH3 Some amino acids Lactate Pyruvate Cytoplasm Mitochondria Pyruvate Fatty acids Acetyl CoA CoA Ketone bodies (in liver) CO2 Citric acid cycle 2 NH3 ATP Some amino acids Figure 22-3 (6 of 7) Electron Transport System Glycogen Glucose 6-phosphate Glucose Liver only Glycerol 2 ATP NH3 Some amino acids Lactate Pyruvate Cytoplasm Mitochondria Pyruvate Fatty acids Acetyl CoA CoA Ketone bodies (in liver) CO2 Citric acid cycle 2 Electron transport system NH3 O2 26-28 ATP ATP Some amino acids + H2O Figure 22-3 (7 of 7) Metabolism: Push-Pull Control • Metabolic balance can shift when enzyme activity is controlled Figure 22-4 Metabolism: Fates of Nutrients in the Fed State Table 22-2 Transport and Fate of Dietary Fats Dietary fats Intestinal lumen Monoglycerides Phospholipids Free fatty acids (FFA) Cholesterol apo Intestinal cells CM Chylomicron FFA Lymph Adipose cells Blood Bile duct Lipolysis by lipases CM lpl FFA Glycerol Reassemble to triglycerides (TG) TG storage CM remnants HDL-C Most cells LDL-C Liver FFA oxidized for energy Cholesterol for synthesis Metabolized Lipoprotein complexes Cholesterol + FFA + Lipoproteins Bile salts KEY apo=apoproteins lpl=lipoprotein lipase LDL=low-density lipoprotein HDL = high-density lipoprotein C=cholesterol Figure 22-5 High LDL-C Levels Increase Heart Disease Risk • LDL-C takes cholesterol from liver to most cells • High LDL-C increases risk of atherosclerosis • Many drugs try to lower cholesterol levels by changing its metabolism • Low HDL is another risk factor for atheroslerosis Figure 22-6 Fasted-State Metabolism 1 Liver glycogen becomes glucose. 2 Adipose lipids become free fatty acids and glycerol that enter blood. Liver glycogen stores Free fatty acids Glycogenolysis -oxidation Energy production Glucose Triglyceride stores Free fatty acids Glycerol Gluconeogenesis Ketone bodies Energy production Glycogen Gluconeogenesis Proteins Pyruvate or Lactate Glucose Ketone bodies Energy production 4 Brain can use only glucose and ketones for energy. Amino acids 3 Muscle glycogen can be used for energy. Muscles also use fatty acids and break down their proteins to amino acids that enter the blood. Figure 22-7 Fasted-State Metabolism 1 Liver glycogen becomes glucose. Liver glycogen stores Free fatty acids Glycogenolysis -oxidation Energy production Glucose Ketone bodies Figure 22-7 (1 of 4) Fasted-State Metabolism 1 Liver glycogen becomes glucose. 2 Adipose lipids become free fatty acids and glycerol that enter blood. Liver glycogen stores Free fatty acids Glycogenolysis -oxidation Energy production Glucose Triglyceride stores Free fatty acids Glycerol Gluconeogenesis Ketone bodies Figure 22-7 (2 of 4) Fasted-State Metabolism 1 Liver glycogen becomes glucose. 2 Adipose lipids become free fatty acids and glycerol that enter blood. Liver glycogen stores Free fatty acids Glycogenolysis -oxidation Energy production Glucose Triglyceride stores Free fatty acids Glycerol Gluconeogenesis Ketone bodies Energy production Glycogen Gluconeogenesis Proteins Pyruvate or Lactate Amino acids 3 Muscle glycogen can be used for energy. Muscles also use fatty acids and break down their proteins to amino acids that enter the blood. Figure 22-7 (3 of 4) Fasted-State Metabolism 1 Liver glycogen becomes glucose. 2 Adipose lipids become free fatty acids and glycerol that enter blood. Liver glycogen stores Free fatty acids Glycogenolysis -oxidation Energy production Glucose Triglyceride stores Free fatty acids Glycerol Gluconeogenesis Ketone bodies Energy production Glycogen Gluconeogenesis Proteins Pyruvate or Lactate Glucose Ketone bodies Energy production 4 Brain can use only glucose and ketones for energy. Amino acids 3 Muscle glycogen can be used for energy. Muscles also use fatty acids and break down their proteins to amino acids that enter the blood. Figure 22-7 (4 of 4)