Renal — Biochemistry MCQs

LYSYL OXIDASE (copper-containing amine oxidase): oxidises lysine and hydroxylysine in collagen/elastin -> allysine -> spontaneous condensation -> CROSSLINKS -> structural integrity of extracellular matrix. Vascular endothelium requires intact ECM for attachment, migration, and regeneration. HOMOCYSTEINYLATION inhibits LYSYL OXIDASE -> impaired ECM crosslinking -> weakened vascular scaffold -> endothelium cannot regenerate efficiently after injury -> perpetuates endothelial damage. Also explains why hyperhomocysteinaemia increases aortic aneurysm risk (elastin crosslinking failure). 📹 [VIDEO LINK]

HYPERHOMOCYSTEINAEMIA and CARDIOVASCULAR DISEASE: independent risk factor for atherosclerosis, coronary artery disease, stroke, peripheral vascular disease, DVT. Mechanisms: (1) endothelial dysfunction, (2) oxidative stress (homocysteine auto-oxidises -> H2O2), (3) LDL oxidation, (4) platelet activation, (5) pro-thrombotic state, (6) smooth muscle cell proliferation. Causes of elevated homocysteine: B12, B6, folate deficiency; CBS deficiency (homocystinuria); renal failure; hypothyroidism; drugs (methotrexate, phenytoin). Treatment: B12 + folate + B6 supplementation. 📹 [VIDEO LINK]

B12 DEFICIENCY PATHWAY: decreased methionine synthase activity -> homocysteine accumulates -> MORE homocysteine enters transsulphuration pathway -> cystathionine beta-synthase (CBS) works harder initially -> CYSTATHIONINE ACCUMULATES. However, FEEDBACK: accumulated homocysteine and/or SAH inhibit CBS indirectly. More precisely: B12 deficiency -> decreased SAM -> decreased allosteric activation of CBS (SAM is a positive allosteric activator of CBS) -> CBS activity actually decreases -> cystathionine production undergoes feedback inhibition. Net: homocysteine elevated, cystathionine may be paradoxically decreased. 📹 [VIDEO LINK]