Metabolism and Energy Balance Chapter 22a Metabolism and Energy Balance

Homeostatic control of metabolism Regulation of body temperature About this Chapter Appetite and satiety Energy balance Metabolism Homeostatic control of metabolism Regulation of body temperature

Food intake is carefully controlled Two competing behavioral states 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)

Methods for measuring energy use 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)

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 Immediate use in energy production Synthesis into needed macromolecules 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 Free fatty acids + glycerol Protein synthesis Glycogenesis Amino acids Glucose Fat stores Lipogenesis Excess glucose Lipogenesis Glycogen stores Body protein Lipolysis Urine Glycogenolysis Glucose pool Gluconeogenesis Free fatty acid pool Range of normal plasma glucose Amino acid pool Metabolism in most tissues Brain metabolism Excess nutrients Figure 22-2

Metabolism in most tissues Glucose Metabolism DIET Most plasma glucose is used for immediate energy production, or is stored as glycogen Carbohydrates Glycogenesis Glucose Fat stores Lipogenesis Excess glucose Glycogen stores Urine Glycogenolysis Glucose pool Range of normal plasma glucose Metabolism in most tissues Brain metabolism Figure 22-2 (1 of 4)

Metabolism in most tissues Fat Metabolism DIET Free fatty acids are used for immediate energy production, or are stored as fat molecules in adipose tissue Fats Free fatty acids + glycerol Fat stores Lipogenesis Lipolysis Free fatty acid pool Metabolism in most tissues Excess nutrients 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 Protein synthesis Amino acids Body protein Glucose pool Gluconeogenesis Range of normal plasma glucose Amino acid pool Figure 22-2 (3 of 4)

Metabolism in most tissues Summary of Metabolism DIET Fats Carbohydrates Proteins Free fatty acids + glycerol Protein synthesis Glycogenesis Amino acids Glucose Fat stores Lipogenesis Excess glucose Lipogenesis Glycogen stores Body protein Lipolysis Urine Glycogenolysis Glucose pool Gluconeogenesis Free fatty acid pool Range of normal plasma glucose Amino acid pool Metabolism in most tissues Brain metabolism Excess nutrients Figure 22-2 (4 of 4)

Biochemical Pathways for Energy Production Overview of Pathways Glycogen Glucose Glucose 6-phosphate Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Lactate Cytoplasm Mitochondria Pyruvate Acetyl CoA Fatty acids CoA Ketone bodies (in liver) CO2 Citric acid cycle 2 ATP Electron transport system NH3 Some amino acids O2 26-28 ATP + H2O Figure 22-3

Interconversions of Glucose Glycogen Glucose Glucose 6-phosphate Liver only Cytoplasm Mitochondria Figure 22-3 (1 of 7)

Glycolysis is Catabolism of Glucose Glycogen Glucose Glucose 6-phosphate Liver only 2 ATP Pyruvate Cytoplasm Mitochondria Figure 22-3 (2 of 7)

Some Amino Acids Can Also Supply Pyruvate Glycogen Glucose Glucose 6-phosphate Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Cytoplasm Mitochondria Figure 22-3 (3 of 7)

Anaerobic Metabolism Produces Lactate Glycogen Glucose Glucose 6-phosphate 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 Glucose 6-phosphate Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Lactate 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 Glucose 6-phosphate Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Lactate Cytoplasm Mitochondria Pyruvate Acetyl CoA Fatty acids CoA Ketone bodies (in liver) CO2 Citric acid cycle 2 ATP NH3 Some amino acids Figure 22-3 (6 of 7)

Electron Transport System Glycogen Glucose Glucose 6-phosphate Liver only Glycerol 2 ATP NH3 Some amino acids Pyruvate Lactate Cytoplasm Mitochondria Pyruvate Acetyl CoA Fatty acids CoA Ketone bodies (in liver) CO2 Citric acid cycle 2 ATP Electron transport system NH3 Some amino acids O2 26-28 ATP + 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 Intestinal lumen Monoglycerides Phospholipids Free fatty acids (FFA) Cholesterol apo Intestinal cells CM Chylomicron FFA Lymph Bile duct Blood Adipose cells CM Lipolysis by lipases lpl FFA Reassemble to triglycerides (TG) TG storage Glycerol CM remnants Most cells HDL-C LDL-C FFA oxidized for energy Liver Cholesterol for synthesis Metabolized Lipoprotein complexes KEY apo=apoproteins lpl=lipoprotein lipase LDL=low-density lipoprotein HDL = high-density lipoprotein C=cholesterol Cholesterol + FFA + Lipoproteins Bile salts 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. Triglyceride stores Liver glycogen stores Free fatty acids Free fatty acids Glycerol Glycogenolysis -oxidation Gluconeogenesis Energy production Ketone bodies Energy production Glucose Glycogen Proteins Gluconeogenesis Pyruvate or Lactate Amino acids Ketone bodies Glucose Energy production 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. 4 Brain can use only glucose and ketones for energy. Figure 22-7

Fasted-State Metabolism 1 Liver glycogen becomes glucose. Liver glycogen stores Free fatty acids Glycogenolysis -oxidation Energy production Ketone bodies Glucose 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. Triglyceride stores Liver glycogen stores Free fatty acids Free fatty acids Glycerol Glycogenolysis -oxidation Gluconeogenesis Energy production Ketone bodies Glucose 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. Triglyceride stores Liver glycogen stores Free fatty acids Free fatty acids Glycerol Glycogenolysis -oxidation Gluconeogenesis Energy production Ketone bodies Energy production Glucose Glycogen Proteins Gluconeogenesis 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. Triglyceride stores Liver glycogen stores Free fatty acids Free fatty acids Glycerol Glycogenolysis -oxidation Gluconeogenesis Energy production Ketone bodies Energy production Glucose Glycogen Proteins Gluconeogenesis Pyruvate or Lactate Amino acids Ketone bodies Glucose Energy production 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. 4 Brain can use only glucose and ketones for energy. Figure 22-7 (4 of 4)