Metabolic Processes Integration and Control

Integration of Metabolic Processes

• All metabolic (and non-metabolic) processes are integrated (or at least interact with each other) in the body.
• The integration of metabolic processes should be considered at two levels: cellular and tissue/whole organism.

Control of Metabolic Processes

• Allosteric regulation, covalent modifications, enzyme regulation, compartmentalization, and metabolic specialization of organs are ways to control metabolic processes.
• Integration of metabolic processes should be considered at two levels: cellular and tissue/whole organism.

Major Metabolic Pathways and their Key Metabolites

Glycolysis

• Glucose-6-phosphate is a critical point in glycolysis and has many possible "fates".
• Pyruvate is the product of glycolysis and a turning point of metabolism depending on the oxidative state of the cell.
• In the absence of oxygen, pyruvate is converted to lactate.
• In the presence of oxygen, pyruvate is converted to Acetyl-CoA.
• Pyruvate can also undergo transamination with the formation of alanine or carboxylation with the formation of oxaloacetate.

Gluconeogenesis

• Gluconeogenesis is a reversal of glycolysis.
• To carry out gluconeogenesis, three reactions of glycolysis must be bypassed: glucose -> glucose 6 phosphate, fructose 6 phosphate -> fructose 1,6 bis phosphate, and phosphoenolpyruvate -> pyruvate.
• Glycolysis and gluconeogenesis are regulated simultaneously, with factors that promote glycolysis simultaneously inhibiting gluconeogenesis, and vice versa.

Krebs Cycle

• Acetyl-CoA is the central compound of all metabolism.
• The Krebs cycle is the oxidation of Acetyl-CoA to two molecules of CO2, regenerating oxaloacetate and producing ATP, NADH, and FADH2.
• Acetyl-CoA can be produced from pyruvate, fatty acid beta-oxidation, or ketogenic amino acid catabolism.
• Anaplerotic pathways rebuild Krebs cycle intermediates.

Pentose-Phosphate Pathway

• The pentose-phosphate pathway produces ribose-5-phosphate for nucleotide synthesis and NADPH for reductive biosynthesis.

Glycogen Synthesis and Degradation

• Glycogen is a "medium-term" form of energy storage located in the liver and muscles.

Antagonistic Effect of Insulin and Glucagon

• Insulin promotes glucose uptake, glycogen synthesis, and fatty acid synthesis, while inhibiting glycogen degradation, gluconeogenesis, and fatty acid mobilization.
• Glucagon has the opposite effects, promoting glycogen degradation, gluconeogenesis, and fatty acid mobilization, while inhibiting glycogen synthesis and fatty acid synthesis.

Adaptation of Metabolism to Reduced Energy Supply

• In the early stage of reduced energy supply (fasting, >2 days), glycogenolysis and gluconeogenesis are the main sources of glucose.
• In the intermediate stage of reduced energy supply (prolonged fasting, up to about 3 weeks), glycogen is virtually depleted, and fatty acid beta-oxidation and ketone body production become the main sources of energy.
• In the long-term reduced energy supply (starvation, more than 3 weeks), protein protection is prioritized, with the transport of lactate and alanine from muscle to liver for glucose synthesis.

Metabolic Specialization of Organs

• The brain has a high energy demand and relies on glucose and ketone bodies for energy.
• The liver processes ingested sugars, proteins, and fats, and synthesizes and distributes lipids, ketone bodies, and glucose.
• Adipose tissue is responsible for lipid synthesis, storage, and mobilization.
• Skeletal muscles have a high ATP demand for muscle contraction and relaxation.

Other Key Points

• The pancreas secretes insulin and glucagon in response to changes in blood glucose levels.
• The portal vein transmits nutrients from the intestine to the liver.
• The small intestine absorbs nutrients and transfers them to the bloodstream.