Synopsis
Connect carbohydrate, lipid, amino-acid and energy metabolism to compartment, feeding state, organ function and the interpretation of common biochemical patterns.
- Metabolic pathways are regulated networks: substrate availability, enzyme activity, compartment and hormonal state determine flux more than memorising an isolated reaction list.
- Glycolysis converts glucose to pyruvate in cytosol and can generate ATP without oxygen; mitochondrial oxidation yields more ATP when oxygen delivery and respiratory machinery are adequate.
- Glycogen buffers short-term glucose supply, hepatic gluconeogenesis supports fasting plasma glucose, and adipose lipolysis plus hepatic ketogenesis become increasingly important with prolonged insulin deficiency or fasting.
Reasoning priorities
Place each reaction in cytosol, mitochondrion, liver, muscle, adipose tissue or circulating blood.
A proposed pathway is impossible if its required enzyme or substrate is absent from that compartment, even when the reaction is chemically plausible.
Worked reasoning
A model tissue has ongoing glycolysis, adequate glucose, impaired mitochondrial reoxidation of NADH and a rising cytosolic NADH-to-NAD+ ratio; no additional clinical signs are assumed.
- Glycolysis requires oxidised NAD+ at the glyceraldehyde-3-phosphate step, so continued ATP generation needs a route that regenerates NAD+.
- Impaired mitochondrial redox disposal prevents normal transfer of reducing equivalents into oxidative phosphorylation and raises cytosolic reduction pressure.
- Lactate dehydrogenase converts pyruvate to lactate while oxidising NADH back to NAD+, allowing glycolysis to continue temporarily.
- The final predicted pattern is increased lactate relative to pyruvate with limited ATP yield compared with complete mitochondrial oxidation.
- Verify the mechanism by checking redox balance: if NAD+ were not regenerated, glycolytic flux would stall despite abundant glucose.