Metabolism and Energetics

Introduction to Cellular Metabolism

Cellular metabolism encompasses all chemical reactions occurring within the body, enabling cells to extract energy and build essential molecules. These reactions are categorized as catabolic (breaking down molecules) or anabolic (building up molecules), with energy transfer typically mediated by ATP.

• Metabolism: The sum of all chemical reactions in the body.

• Catabolism: Breakdown of complex organic molecules to release energy.

• Anabolism: Synthesis of complex molecules from simpler ones, requiring energy.

• Nutrient Pool: The collection of organic building blocks (fatty acids, glucose, amino acids) available for cellular metabolism.

• ATP: The primary energy carrier in cells.

Example: ATP is generated from glucose during cellular respiration, fueling muscle contraction and biosynthesis.

The Role of the Nutrient Pool in Cellular Metabolism

The nutrient pool provides substrates for both catabolic and anabolic reactions. Cells utilize fatty acids, glucose, and amino acids to generate ATP and maintain metabolic reserves.

• Triglycerides are broken down into fatty acids, which enter mitochondria for ATP production.

• Glycogen is converted to glucose, then to pyruvic acid (3-carbon chain) and acetyl-CoA (2-carbon chain) for mitochondrial ATP synthesis.

• Proteins are broken down into amino acids, which can be metabolized for energy.

• Metabolic reserves: The nutrient pool of each cell contributes to the body's overall energy reserves.

• Nutrient distribution: Digestion, liver, adipocytes, skeletal muscle, and neural tissue all play roles in nutrient storage and utilization.

• Enzymatic synthesis: Cells synthesize needed molecules from available nutrients.

Additional info: Glycogenolysis, glycogenesis, glycolysis, gluconeogenesis, and protein/fat conversion to glucose are key metabolic pathways.

The Citric Acid Cycle (TCA Cycle)

The TCA cycle, also known as the citric acid or Krebs cycle, is central to cellular respiration. Its main function is to remove hydrogen atoms from metabolic intermediates and transfer them to coenzymes NAD and FAD.

• Pyruvate is converted to acetyl-CoA, entering the TCA cycle.

• NAD and FAD act as electron carriers, forming NADH and FADH2.

• Electrons are transported to mitochondria for ATP production.

Electron Transport System and ATP Synthesis

Oxidative phosphorylation occurs in mitochondria, where electrons from NADH and FADH2 are transferred through the electron transport chain to oxygen, forming water and generating a proton gradient used to synthesize ATP.

• Electron transport proteins (cytochromes): Facilitate electron transfer.

• ATP Synthase: Utilizes the proton gradient to produce ATP.

• Equation:

Example: The process is analogous to water turning a turbine to generate electricity.

Digestion and Metabolism of Organic Nutrients

Digestion breaks down food into absorbable molecules, which are distributed via the bloodstream. The process involves mechanical and enzymatic actions in the oral cavity, stomach, and intestines.

• Saliva and chewing initiate digestion.

• Stomach acid and enzymes further break down food.

• Pancreatic enzymes in the duodenum digest carbohydrates, lipids, proteins, and nucleic acids.

• Absorption occurs mainly in the jejunum.

• Indigestible materials are processed in the large intestine.

• Liver regulates nutrient levels in the blood.

Carbohydrate Metabolism

Carbohydrates are the preferred substrate for ATP production. Digestion begins in the mouth and continues in the intestines, with enzymes breaking down polysaccharides to monosaccharides.

• Salivary amylase: Initiates carbohydrate digestion.

• Pancreatic amylase: Continues digestion in the duodenum.

• Enzymes (maltase, sucrase, lactase): Convert disaccharides to monosaccharides.

• Glucose: Main energy source; can be oxidized for ATP, stored as glycogen, or used for biosynthesis.

• Glycolysis: Glucose is split into two pyruvate molecules.

Fate of Glucose in Glycolysis

Glycolysis is the first step in cellular respiration, occurring in the cytosol. It produces pyruvic acid and ATP. In the absence of oxygen, pyruvic acid is converted to lactic acid (anaerobic); with oxygen, it enters mitochondria for further ATP production (aerobic).

• Anaerobic metabolism: Yields 2 ATP per glucose.

• Aerobic metabolism: Yields 36 ATP per glucose.

• Equation:

Lipid Transport and Distribution

Lipid digestion begins in the mouth and continues in the stomach and intestines. Lipids are emulsified by bile salts and absorbed as micelles, then packaged into chylomicrons for transport.

• Lingual lipase: Initiates triglyceride digestion.

• Bile salts: Emulsify lipids in the duodenum.

• Chylomicrons: Transport dietary lipids via lymphatic system.

• Lipoproteins: Four classes—chylomicrons, VLDL, LDL, HDL.

Additional info: Desirable blood cholesterol is below 200 mg/dL; low LDL:HDL ratio is preferred.

Fate of Fatty Acids in Lipid Metabolism

Lipids are oxidized for ATP, stored in adipose tissue, or used for structural and functional molecules. Lipolysis and lipogenesis regulate lipid catabolism and anabolism.

• Lipolysis: Triglycerides are broken down for energy (beta-oxidation).

• Lipogenesis: Formation of lipids from glucose or amino acids.

• Triglyceride storage: Occurs mainly in subcutaneous adipose tissue.

Protein Metabolism and Use as Energy Source

Protein digestion is complex, involving mechanical and chemical breakdown. Proteins are used for structural, functional, and energy purposes. Catabolism and anabolism regulate protein turnover.

• Protein catabolism: Amino acids are deaminated, forming ammonia and urea.

• Amination: Addition of amino group to form amino acids.

• Transamination: Transfer of amino group to form new amino acids.

• Urea cycle: Converts toxic NH4+ to urea for excretion.

• Protein anabolism: Formation of peptide bonds to synthesize new proteins.

Absorptive and Postabsorptive Metabolic States

Metabolic activity alternates between absorptive (after eating) and postabsorptive (fasting) states, regulated by hormones and nutrient availability.

• Absorptive state: Lasts ~12 hours/day; ATP is produced from glucose, lipids are stored, and proteins synthesized. Insulin is the main hormone.

• Postabsorptive state: Lasts ~12 hours/day; stored triglycerides and proteins are catabolized for energy. Glucagon, glucocorticoids, and epinephrine regulate this state.

• Ketogenesis: Formation of ketone bodies during prolonged fasting or starvation.

Metabolic Disorders

Several disorders arise from nutritional or biochemical imbalances, affecting metabolism and health.

• Anorexia nervosa: Self-induced starvation due to psychological factors.

• Bulimia: Binge eating followed by purging.

• Obesity: Excess body weight; regulatory (common) or metabolic (rare).

• Phenylketonuria (PKU): Genetic disorder; inability to convert phenylalanine to tyrosine.

• Kwashiorkor: Protein deficiency despite normal caloric intake; causes edema and liver enlargement.

• Ketoacidosis: Excess ketone bodies due to lipid metabolism; can cause acidosis.

• Gout: High uric acid levels; uric acid crystals in joints cause inflammation.

Energetics and Thermoregulation

Body temperature is regulated by balancing heat production and loss. Metabolic rate reflects the rate of energy expenditure, with basal metabolic rate (BMR) indicating energy use at rest.

• BMR: Average adult BMR is 1680 Cal/day.

• Heat production: All ATP-generating reactions produce heat.

Regulation of Food Intake

The hypothalamus contains feeding and satiety centers that regulate appetite, influenced by hormones and external factors.

• Feeding center: Stimulates appetite.

• Satiety center: Suppresses appetite.

• Neuropeptide Y: Increases appetite.

• Ghrelin: Increases appetite.

• Leptin: Suppresses appetite.

Mechanisms of Heat Gain and Heat Loss

Heat is transferred by radiation, convection, evaporation, and conduction. Only a fraction of catabolic energy is captured as ATP; the rest is lost as heat.

• Radiation: Heat transfer via infrared waves.

• Convection: Heat transfer by movement of air or liquid.

• Evaporation: Conversion of liquid to vapor; main defense against overheating.

• Conduction: Heat transfer to objects in contact with the body.

• Heatstroke: Severe disorder from extreme heat; reduced sweating and high core temperature.

Homeostatic Mechanisms for Body Temperature Regulation

Heat-loss and heat-gain centers in the hypothalamus coordinate responses to maintain constant body temperature.

• Heat-loss center: Behavioral changes, vasodilation, sweating, increased respiratory rate.

• Heat-gain center: Nonshivering thermogenesis (hormonal), shivering, vasoconstriction, heat conservation via deep veins.

Example: Vasodilation increases blood flow to skin, enhancing heat loss; shivering increases muscle activity to generate heat.