Physiology Metabolism

• Glycogenolysis is the breakdown of glycogen to release glucose molecules.
• Gluconeogenesis occurs mainly in the liver but also takes place to some extent in the kidneys.
• The liver is the main site of gluconeogenesis, which involves the conversion of non-carbohydrate sources into glucose.
• Gluconeogenesis is the process by which non-carbohydrate sources are converted into glucose, such as lactate or amino acids.
• The liver plays an important role in regulating blood sugar levels through its ability to store excess glucose as glycogen and convert it back into glucose when needed.
• Insulin promotes the uptake of glucose from the bloodstream into cells, where it can be used for energy production or stored as glycogen.
• The process involves converting non-carbohydrate sources such as lactate, amino acids, or fatty acids into glucose through several steps.
• In the first step, pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate using ATP and CO2.
• Oxaloacetate then undergoes decarboxylation by phosphoenolpyruvate carboxykinase (PEPCK) to form PEP.
• Non-carbohydrate precursors include lactate, pyruvate, alanine, amino acids (glutamine), and glycerol from lipid metabolism.
• Lactate can be used as an energy source during exercise when oxygen supply cannot meet demand.
• Lactate produced by muscle cells during anaerobic respiration can be converted back to pyruvate through oxidation and then enter the Krebs cycle or be used as a substrate for gluconeogenesis.
• During intense exercise, there may not be enough oxygen available to convert pyruvate from glycolysis into carbon dioxide and water through aerobic respiration.
• Liver cells have enzymes that can break down proteins (proteases) and fats (lipase).
• Protein catabolic pathways involve breaking down protein molecules into their constituent amino acids.
• In this case, pyruvate is reduced to form lactic acid instead.
• Pyruvate can be converted to phosphoenolpyruvate (PEP) via PEP carboxylase, which requires ATP and carbon dioxide.
• • Glucostatic theory: blood [glucose]
  • ↓ blood glucose → stimulate feeding center & inhibit satiety center
  • ↑ blood glucose → inhibit feeding center & stimulate satiety center
• • Lipostatic theory: lipid & adipose tissue
  • Negative feedback regulation of feeding center
  • ↑ production of leptin hormone → 

  inhibit neuropeptide Y release → 

  ↓ stim. of feeding center 
• • Ghrelin (hunger hormone)
  • ↑ feelings of hunger
  • Stimulates growth hormone release
• • CCK & GLP-1 
  • ↓ feelings of hunger
• Influences of Feeding vs. Satiety:

  • Other factors
  • Eating & chewing, gut distension
  • Sight, smell, taste
  • Cravings: physiological & psychological
• Total energy = energy stored + energy in - energy out
• Energy stored: energy that is not needed for immediate work

  • Glycogenesis
  • 1 glycogen can contain 55,000 glucose molecules
  • Liver (100 g) vs. skeletal muscle (200 g)
  • Other cells - small amounts
• Lipogenesis:

  • Subcutaneous & abdominal adipose tissues
• Energy in: food

  • Potential energy stored in chemical bonds
  • Food calorimetry: measuring energy in food
  • Direct calorimetry: measures heat production
  • Measured in kcal (1000 calories)
• Energy out: work + heat production

  • Work: cellular & body levels
  • Transport: between compartments
  • Mechanical: internal work within cells & heart beats, external work of movement
  • Chemical: storage of energy in chemical bonds
• Metabolism: energy used by body

  • Indirect calorimetry: measures metabolism
  • O2 consumption or CO2 or heat production vs. energy metabolized
  • Metabolic rate = L O2 consumed/day x 4.825 kcal/L O2
• Energy out: work + heat production

  • Metabolic rates
  • Basal metabolic rate (BMR) (kcal/day or cal/hr)
  • Lowest amount of energy required by body
• • Resting metabolic rate (RMR) (kcal/day or cal/hr)
  • Close approximation of BMR
  • Awake but at rest
  • 12 hr fast
  • Comfortable temperature: thermoneutral ≈21.8 – 30 °C: 82-86 °F
• • Metabolic rate (MR) (kcal/day or cal/hr)
  • Energy expenditure at any time: BMR + any activity
• • Factors that influence metabolic rate
  • BMR
  • Age * 
  • Sex *
  • Lean muscle mass vs. body fat *
  • Hormones
  • Thyroid hormone (TH) & epinephrine (E): calorigenic effect
  • Genetics
  • MR
  • Food-induced (diet-induced) thermogenesis
  • Rapid increase in MR due to processing of food by the liver
  • Protein > Carbs > Lipids 
  • Muscle activity *
  • Skeletal muscle can dramatically ↑ MR
• • Altering calorie intake: body attempts to maintain weight within a range
  • ↑ calorie intake → ↑ metabolic expenditure (including BMR)
  • ↓ calorie intake → ↓ metabolic expenditure (including BMR)
• • Exercise: ↑ caloric expenditure
  • Short term effects: immediate calorie expenditure
  • Long term effects: 

  1. lowers weight set point  
  2. ↑ metabolic demand w/ ↑ muscle mass
• • Fed-state or absorptive state
  • Absorption of nutrients from the GI tract

  1. Nutrients available for use by cells
  2. Excess nutrients stored in cells for later use

  • Liver, muscles, adipose
• • Fasted-state or post-absorptive state
  • GI tract is empty

  1. Nutrients taken from body stores

  • Liver, muscles, adipose

  1. Nutrients made available to cells
• • Plasma – nutrient pools available to cells
  • Fed-state or absorptive state: absorbed from GI tract & used or stored
  • Fasted-state or postabsorptive state: released from storage & added to nutrient pool
• • Nutrient conversions
  • Catabolism
  • Anabolism
• • Glycogenesis
  • All cells 
  • Liver (100 g) & muscle (200 g)
• • Glycogenolysis 
  • All cells
  • Liver & muscle