Vertebrate Metabolism and Metabolic Control

Liver: Functions in both catabolic and anabolic pathways to regulate blood chemistry, specifically carbohydrate and amino acid levels. It is responsible for plasma protein synthesis and the metabolism of excess amino acids and foreign molecules.
Adipose Tissue: Primarily a storage tissue for triacylglycerols (TAG).
- White Adipose: Active in fatty acid synthesis and the pentose phosphate pathway (specifically for NADPH) under high-energy conditions.
- Brown Adipose: Features high mitochondria content and high blood flow; generates heat through proton uncoupling via thermogenin.
Muscle:
- Skeletal Muscle: Uses glucose when active and fatty acids at rest. Accounting for $30\%$ of resting $O_2$ consumption, it may undergo protein degradation during fasting to conserve energy.
- Cardiac Muscle: Requires a constant supply of oxygen. Fuels vary by state, utilizing glucose and fatty acids when fed, and shifting to fatty acids and ketone bodies during other times.
Brain: Comprising $2\%$ of body mass, it utilizes $20\%$ of total energy for membrane potentials. It relies on glucose or ketone bodies, lacks glycogen stores, and does not export nutrients. Metabolic control is managed via the Hypothalamus and pituitary gland.

Energy Reserves: Glycogen provides a small portion of energy compared to the bulk storage in adipose tissue ( $2400-7200\,kcal/day$ ).
The Sprinter ( $100\,m$ ):
- Expenditure: $200\,kJ/min$ ( $3.3\,kJ/s$ ).
- Fuel: Anaerobic (phosphocreatine/glucose).
- Fatigue: Increased intracellular proton concentration (lowered pH due to lactic acid).
The Marathoner ( $42.2\,km$ ):
- Expenditure: $84\,kJ/min$ (Total: $12000\,kJ$ ).
- Fuel: Aerobic (glucose, fatty acids, glycogen, triacylglycerols).
- Fatigue: Depletion of muscle glycogen reserves.

Feeding Phase (Insulin): Triggered by hormones like gastrin, secretin, and cholecystokinin. Pancreatic b-cells release insulin.
- Metabolic Effects: Increases glucose uptake (via GLUT4), glycogen synthesis, glycolysis, and fatty acid/TAG synthesis.
- Target Enzymes: Glucokinase, Glycogen synthase, PFK-1 (via PFK-2), and Acetyl-CoA carboxylase.
Fasting Phase (Glucagon): Pancreatic a-cells release glucagon.
- Metabolic Effects: Increases glycogen breakdown, gluconeogenesis (using amino acids, glycerol, and oxaloacetate), and fatty acid mobilization.
- Target Enzymes: Glycogen phosphorylase, FBPase-2, and Hormone-sensitive lipase.
- Overnight Fast: Norepinephrine release helps mobilize fatty acids for muscle, saving glucose for the brain.
Prolonged Fasting/Starvation: Blood glucose is sustained by muscle breakdown initially. Eventually, the brain shifts to ketone body utilization to reduce muscle wasting.

Cortisol: A glucocorticoid from the adrenal gland that functions on a long-term scale.
Action: Stimulates protein breakdown in muscle and TAG mobilization in adipose tissue to increase blood glucose.
Long-term Effects: Results in decreased muscle and bone mass and an impaired immune response.

Gluconeogenesis Problems: Exercises involve calculating requirements and ATP production for converting threonine and tyrosine to glucose, accounting for NADH, FADH_2, and acetyl-CoA yields in the mitochondria.