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Unit 7: Metabolism and Energy Balance

1. Metabolic Primer

  • Overview of metabolic concepts and key factors influencing metabolism
  • Core focus includes:
    • Regulation of Eating
    • Insulin:
    1. Secretion
    2. Action
    3. Diabetes Mellitus
    • Endocrine Response to Hypoglycemia: roles of
    1. Glucagon
    2. Cortisol
    3. Epinephrine
    • Other Hormones Affecting Metabolism:
    1. Thyroid Hormone
    2. Growth Hormone
    • Calcium Homeostasis

2. Regulation of Metabolism

  • Definition:
    • “A set of life-sustaining chemical transformations within the cells of living organisms”
  • Metabolism:
    • Energy substrates (carbs, fats, proteins) are either stored (anabolic) or broken down (catabolic)
  • Regulation Mechanisms:
    • Endocrine Regulation:
    • Role of endocrine pancreas in metabolism: insulin/glucagon ratio
    • Neural Regulation:
    • Regulation of food intake

3. Ingested Energy: Fates of Biomolecules

  • Ingested biomolecules have three potential fates:
    1. Fuel: Metabolized for energy
    2. Build: Synthesis reactions for tissue growth and maintenance
    3. Store: As glycogen (in liver and muscles) or fat
  • Metabolism divided into two states:
    • Fed (Absorptive State):
    • Anabolic state where digestion products are absorbed and used for synthesis or storage
    • Fasted (Postabsorptive State):
    • Catabolic state where the body utilizes stored nutrients
  • Nutrient Pools Available for Immediate Use:
    • Glucose
    • Free Fatty Acids
    • Amino Acids

4. Control of Metabolism by Enzymes

  • Enzymes determine the direction of metabolic reactions:
    • Fed State:
    • Insulin promotes glycogen synthesis, inhibits glycogen breakdown
    • Fasted State:
    • Glucagon promotes glycogen breakdown and gluconeogenesis

5. Interconversions of Nutrients

  • Key metabolic pathways:
    • Carbohydrates to Glycogen:
    • Process:
      • Glycogen → Glucose → Glyceraldehyde-3-PO4
    • Fats:
    • Triglycerides (TGs) → Glycerol → Acetyl CoA → Fatty Acids
    • Proteins:
    • Amino acids can be derived from muscle proteins or synthesized

6. Nutrient Storage During the Fasted State

  • Carbohydrates:
    • Glycogen in the liver can be broken down to free glucose
    • Muscle glycogen cannot be exported as free glucose
  • Fats:
    • Triglycerides in adipose tissue provide energy via lipolysis, releasing glycerol and fatty acids
    • Liver can produce ketone bodies from fatty acids through ketogenesis
  • Proteins:
    • Muscle proteins can be converted to amino acids, either used within muscle or sent to the liver for gluconeogenesis

7. Ketogenesis and Energy Production

  • Ketogenesis occurs when lipolysis exceeds the capacity of the TCA cycle, producing ketone bodies as energy substrates
  • Importance during starvation or low-carbohydrate diets
  • Dangers of ketogenesis:
    • High levels of certain ketone bodies may cause ketoacidosis, disrupting acid-base balance

8. Homeostatic versus Non-Homeostatic Eating

  • Homeostatic Eating:
    • Driven by metabolic signals; eating when energy reserves are low
  • Non-Homeostatic Eating:
    • Driven by cognitive or emotional factors (e.g., boredom, stress), occurs despite adequate energy stores

9. Environmental and Lifestyle Influences on Eating

  • Factors influencing appetite include:
    • Taste and smell
    • Cost and availability of food
    • Environmental cues (e.g., advertising, social settings)

10. Hypothalamic Regulation of Eating Behavior

  • Two Centers in the Hypothalamus:
    • Hunger (feeding) center
    • Satiety center
  • Theories of Regulation:
    • Glucostatic Theory: energy intake is regulated by plasma glucose levels
    • Lipostatic Theory: input from fat stores regulates food intake (discovery of leptin in 1994)

11. Leptin and Obesity

  • Leptin:
    • Secreted by adipose tissue, regulates appetite and energy balance
  • The ob/ob mouse model showed leptin's role in body weight regulation
  • Leptin Resistance:
    • Occurs in many obese individuals, affecting appetite control

12. Gut Signals for Appetite Regulation

  • Appetite Inhibitors:
    • Stretch receptors in stomach, CCK in upper intestine, PYY in lower intestine
  • Appetite Stimulators:
    • Ghrelin secreted by the empty stomach

13. Hormonal Influence on Appetite

  • Neuropeptide Y: key neurotransmitter that stimulates appetite
  • Interaction of hormones and neuropeptides (e.g., leptin, ghrelin) plays a complex role in appetite modulation

14. Modern Implications on Obesity

  • Modern societal challenges leading to obesity:
    • Constant availability of food
    • Exposure to cues that stimulate food intake
    • The absence of natural selection pressures for leanness

15. Leptin Deficiencies in Humans

  • Cases identified in individuals with specific genetic mutations affecting leptin production
  • Potential for leptin treatment to restore normal body weight

16. Insulin: Secretion and Action

  • Insulin Release Factors:
    • Increased plasma glucose and amino acids levels
    • Hormonal signals (e.g., GLP-1, GIP)
    • Autonomic nervous system input (parasympathetic stimulation)
  • Insulin Effects:
    • Promotes glucose uptake in muscle and adipose tissue, enhanced glycogenesis, fat synthesis, and protein synthesis

17. Diabetes Mellitus

  • Defined by hyperglycemia due to:
    • Inadequate insulin secretion (Type 1)
    • Abnormal cellular response to insulin (Type 2)
  • Common features include metabolic dysregulation and associated health risks

18. Glucagon: Mechanisms and Effects

  • Antagonizes insulin, produced by alpha cells of the pancreas
  • Primary function: Prevent hypoglycemia through glycogenolysis and gluconeogenesis in the liver

19. Role of Cortisol and Stress Response

  • Produced by adrenal glands, impacts metabolism significantly
  • Stress response involves increase in cortisol, affecting various body systems, including immune suppression

20. Overview of Thyroid Hormones

  • Thyroid hormones are crucial for metabolic regulation and are derived from tyrosine and iodine
  • Main forms: Thyroxine (T4) and Triiodothyronine (T3)
  • Functions include thermogenesis, modulation of metabolism, and impact on growth and development

21. Calcium Homeostasis

  • Crucial for various physiological functions including muscle contraction and neurotransmitter release
  • Regulated by parathyroid hormone, vitamin D3, and calcitonin
  • Bone remodeling is continuous and involves complex interactions between osteoblasts and osteoclasts