Lysine is essential (humans cannot synthesize) and the most-abundant basic amino acid. Catabolism goes via saccharopine pathway (LKR / SDH — bifunctional enzyme deficient in hyperlysinemia) → α-aminoadipate → α-ketoadipate → glutaryl-CoA → acetyl-CoA + CO2. Lysine is the precursor for CARNITINE biosynthesis (multi-step: lysine → trimethyllysine → β-hydroxy-trimethyllysine → 4-N-trimethylaminobutyraldehyde → γ-butyrobetaine → L-carnitine; the last step is hydroxylated by BBOX1, which is also a target of the ketogenic-mimetic mildronate / meldonium). Hyperlysinemia is generally benign; glutaric aciduria type 1 (GCDH deficiency, downstream) causes a macrocephalic neonatal encephalopathy.
Organ Systems
musculoskeletal
digestive
Pathway Steps
lysine → saccharopine — via LKR (α-aminoadipic semialdehyde synthase, bifunctional LKR-SDH). The saccharopine pathway (bifunctional AASS) is the main lysine catabolic route; defects cause hyperlysinemia (usually benign). Lysine is strictly ketogenic, ultimately yielding acetyl-CoA via α-aminoadipate and glutaryl-CoA.
saccharopine → alpha-aminoadipate — via SDH (saccharopine dehydrogenase) + glutamate semialdehyde branch. Continuing to α-aminoadipate, the pathway heads toward glutaryl-CoA; a downstream block at glutaryl-CoA dehydrogenase causes glutaric aciduria type I (a treatable cause of acute striatal injury) — tying lysine catabolism to a key neurometabolic disease.
lysine → l-carnitine — via multi-step (TMLD + 4-OH-TML + TMABA → BBOX1) — only in liver + kidney + brain. Protein-bound trimethyl-lysine is also the carbon skeleton for endogenous carnitine synthesis, completed in liver/kidney by γ-butyrobetaine hydroxylase (BBOX1) — the step inhibited by meldonium (mildronate).