Senior-clinician companion to introductory Biochemistry notes. Educational use only.
A Word From Your Senior
Biochemistry is most useful when it stops being a pathway chart and becomes an explanation for why this patient, at this time, has this pattern of results.
Substrates, Energy, and Flux
Carbohydrates, lipids, and amino acids are fuels, structural materials, and signalling precursors. ATP couples energy-releasing reactions to cellular work, but cells also depend on redox carriers, ion gradients, compartmentalisation, oxygen delivery, and intact mitochondria.
Enzymes lower activation energy; they do not change reaction equilibrium. Rate depends on substrate, enzyme abundance, cofactors, inhibitors, pH, temperature, cellular location, and regulation. A blood concentration is a snapshot of production, distribution, transformation, and clearance.
Fed, Fasting, and Illness
Insulin generally favours storage and anabolic pathways; glucagon and counter-regulatory hormones support fuel mobilisation. This teaching contrast is useful but incomplete. Sepsis, trauma, pregnancy, liver disease, renal failure, endocrine disorders, alcohol, and drugs reshape metabolism.
During fasting, hepatic glycogenolysis supports glucose early, while gluconeogenesis and lipid-derived fuels become increasingly important. Red blood cells still require glucose because they lack mitochondria; the brain adapts partly to ketones during prolonged fasting but does not become glucose-independent.
DNA Is Not Destiny
DNA encodes biological information, but phenotype also reflects regulation, epigenetic state, environment, mosaicism, penetrance, and gene-gene interaction. A variant classification is evidence-based and may change; "positive" does not automatically mean causal.
Bedside Case
A patient with diabetes has high anion-gap metabolic acidosis and ketonaemia. Think in linked mechanisms: insulin deficiency and counter-regulatory hormones increase lipolysis and ketogenesis; osmotic diuresis causes water and electrolyte loss; measured serum potassium may be normal or high despite major total-body potassium depletion. Treatment therefore requires protocol-led monitoring, not correction of glucose alone.
Accuracy Guardrails
- ATP is not literally stored currency; it is continuously generated and consumed.
- Vitamins are not harmless "helper sparks" at any dose; deficiency and excess can both cause disease.
- A reference interval is not a universal healthy range; method, population, timing, and pre-test probability matter.
- Haemolysis, sampling time, posture, fasting state, supplements, and medicines can distort results.
- Do not diagnose an inborn error or genetic syndrome from one abnormal metabolite or unverified variant.
Ward-Round Questions
- Is this result increased by production, cell release, or reduced clearance?
- Could collection or assay interference explain it?
- Which paired result should change in the same mechanism?
- Does the time course fit the proposed pathway?
Trusted Starting References
- NCBI Bookshelf: Medical Biochemistry (opens in a new tab)
- Clinical and Laboratory Standards Institute (opens in a new tab)
- ClinGen (opens in a new tab) for variant interpretation resources.