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START HERE — how to read palmitoylcarnitine + CoA → palmitoyl-CoA + carnitine
A carnitine-acyltransferase cartoon on the rat CPT2 frame that actually exists: 2RCU (1.78 Å) chain A with a hexadecanoylamino-carnitine analog (BUJ). Human CPT2 (P23786) has no PDB — species hedge. Transit 1–25 is not this mesh. BUJ is an amide analog, not the physiological ester. CoA-SH, palmitoyl-CoA, and free carnitine are [schematic]. His372 ★ on this mesh is rat CPT2 His372 (UniProt human His372 compiled, ECO:0000250). No covalent residue intermediate (A-page). Gold is H⁺. Blue is sulfur nucleophile, not hydride. Measured Å are deposited 2RCU pairs only. Schematic Å are not geomClaims. Reverse of CPT1, matrix. 2DEB apo is a named companion, not this ternary. CPT1A/CACT are other pages.
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Crystal structures
PDB 2RCU — rat CPT2 + hexadecanoylamino-carnitine analog, 1.78 Å (Rufer 2007). Coordinates are public. This is rat CPT2 (P18886), not human. Human CPT2 UniProt P23786 has no PDB. 2DEB is rat CPT2 apo — named companion, not this ternary. Transit peptide 1–25 is not this mesh (Cα 32–658).
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Mechanism — carnitine transesterification (reverse of CPT1)
UniProt P23786 EC 2.3.1.21: palmitoylcarnitine + CoA → palmitoyl-CoA + carnitine. His372 is the compiled proton acceptor (ECO:0000250). On this mesh the catalytic histidine is rat His372. CPT1A (OMM) and CACT (IMM antiport) are other pages. Source: UniProt P23786 · Rufer 2007
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0 — Setup: empty CPT2 pocket
2RCU occupancy is the amide analog (BUJ). The pocket is shown empty so ordered binding can start. Opaque, run:null (no autoplay). Human CPT2 has no PDB; this mesh is rat. His372 ★ is the catalytic histidine on this frame.Source: PDB 2RCU (1.78 Å)
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① — Palmitoylcarnitine analog binds
Deposited hexadecanoylamino-carnitine (BUJ) docks as teaching palmitoylcarnitine — analog occupancy, amide not ester. Not free carnitine and not palmitoyl-CoA. 2DEB apo is not this ternary.Source: PDB 2RCU ligand BUJ
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② — CoA-SH binds
[schematic] CoA-SH docks with the thiol toward the analog carbonyl / His372 — not deposited on 2RCU. His372 NE2 ⋯ analog N2 = 2.80 Å is deposited 2RCU (amide N, not ester O). Schematic CoA distances are not geomClaims.Source: 2RCU His372/BUJ N2; schematic CoA
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③ — His372 takes the CoA thiol proton
(hypothetical, lit.-based) Gold H⁺ rides from CoA thiol to His372 NE2. On this mesh the atom is rat CPT2 His372 (UniProt human His372 compiled). Reverse of CPT1 (there the base takes carnitine OH). His372 NE2 ⋯ Tyr120 OH = 3.95 Å.Source: compiled CPT His · UniProt P23786 ECO:0000250 · 2RCU His372/Tyr120
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④ — CoA-S attacks carbonyl → acyl-CoA + carnitine
(hypothetical, lit.-based) Blue nucleophile rides from CoA S to the analog carbonyl. Palmitoylcarnitine analog + CoA-SH fade in place to schematic palmitoyl-CoA and schematic L-carnitine. Carnitine-O⁻ reprotonation (His regeneration) is not drawn. A-page. Slow-motion on purpose. The analog is amide, not ester.Source: compiled carnitine acyltransferase · UniProt P23786
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⑤ — Acyl-CoA and carnitine leave — ACADM next
[schematic] Palmitoyl-CoA and L-carnitine depart opposite ways. Teaching product is C16 palmitoyl-CoA. ACADM (next) is taught on octanoyl-CoA (C8) — a chain-length jump, not the same molecule. This page does not antiport across the IMM and does not run CPT1A. Rat distances are not human geomClaims.Source: β-oxidation bookkeeping · EC 2.3.1.21
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How to read this page — a first-pass primer
First pass: Setup (empty rat CPT2 pocket, His372 ★, species hedge) → ① analog palmitoylcarnitine docks → ② schematic CoA-SH docks → ③ gold H⁺ CoA-SH → His372 → ④ blue CoA-S → carbonyl, fade to acyl-CoA + carnitine → ⑤ acyl-CoA and carnitine leave opposite ways; ACADM next (C16 → C8 teaching jump). Second pass: 2.80 / 2.53 / 3.95 Å are crystal facts on 2RCU; CoA, palmitoyl-CoA, and free carnitine are [schematic]; analog is amide not ester. Teaching product is C16; ACADM is taught on C8. Third pass: open “Disagreements” for rat ≠ human, amide analog vs ester substrate, 2DEB apo vs this ternary, and CPT1A/CACT vs this page.
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Chemistry primer — reverse transesterification
CPT2 in the matrix transfers the acyl chain from carnitine back onto CoA so β-oxidation can start. His372 is the compiled general base that takes the CoA thiol proton; the deprotonated sulfur attacks the acylcarnitine carbonyl; carnitine leaves. Gold is H⁺. Blue is sulfur nucleophile, not hydride. This is not CACT (antiport) and not CPT1A (OMM, reverse direction).
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Words used on screen — species hedge · analog · His372 ★
Species hedge — the mesh is rat CPT2; human CPT2 has no PDB. Analog — BUJ is hexadecanoylamino-carnitine (amide), taught as palmitoylcarnitine, not the physiological ester. His372 ★ — PDB id on this rat frame; UniProt human His372 in the drawer. CoA stub — pantetheine cartoon, not full 3′-phospho-ADP-CoA.
Legend & Fidelity
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Mechanism fidelity — measured vs. inferred
The measured layer: 2RCU (1.78 Å) rat CPT2 + BUJ analog; His372 NE2 ⋯ analog N2 = 2.80 Å; Tyr486 OH ⋯ analog O13 = 2.53 Å; His372 NE2 ⋯ Tyr120 OH = 3.95 Å. The inferred layer ([schematic]): CoA-SH stub, palmitoyl-CoA, free carnitine, transferring H⁺ / nucleophile spheres, product leave. Binding order is compiled staging, not a kinetic fit. The protein mesh is static. Schematic CoA Å are not geomClaims. The analog is amide, not ester.
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Disagreements on record
(a) Species. 2RCU is rat CPT2 (P18886), not human (P23786). Human CPT2 has no PDB. (b) Amide vs ester. BUJ is hexadecanoylamino-carnitine; the physiological substrate is the ester. His372⋯N2 = 2.80 Å is analog N, not ester O. (c) 2DEB vs 2RCU. Apo companion, not this ternary. (d) Transit 1–25 is not this mesh (Cα 32–658). (e) CPT1A is the reverse reaction on the OMM; CACT is IMM antiport. (f) Concerted vs split proton/attack — this page splits ③ then ④ for 1-event/1-step teaching. (g) Membrane association of the N-terminal insert is not this cartoon.
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Regulation — matrix localization · isoforms
CPT2 is the matrix enzyme of the carnitine shuttle. The N-terminal insert associates with the inner membrane (Rufer 2007) — not a catalytic event on this page. This mesh is rat CPT2 teaching. CPT1A (OMM) and CACT (IMM) are other pages. Human CPT2 deficiency alleles are named, not simulated.Source: UniProt P23786 · PDB 2RCU · Rufer 2007
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Kinetics scope (no measured timecourse on this page)
One palmitoylcarnitine + CoA → palmitoyl-CoA + carnitine event is drawn, not a steady-state run. Compiled BRENDA values for EC 2.3.1.21 are not re-asserted here — no measured kcat/Km on this page [schematic]. Pair with a kinetics chapter.Source: BRENDA EC 2.3.1.21 — no kcat/Km re-asserted
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Sequence
Human CPT2 UniProt P23786 · NCBI Gene 1376 (no PDB). This screen uses rat CPT2 numbering (His372 on 2RCU). Chain A. Cα 32–658. Transit 1–25 not this mesh.
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Simulation map — what you see is what is written
Setup = 2RCU pocket empty (opaque, no autoplay). ① analog palmitoylcarnitine moves in. ② schematic CoA-SH moves in. ③ gold H⁺ CoA-SH → His372. ④ slow-mo: blue CoA-S → carbonyl; analog+CoA fade to acyl-CoA + carnitine. ⑤ acyl-CoA and carnitine leave opposite ways. Only these events move.
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Sources — bibliography of this page
S1 — PDB 2RCU: rat CPT2 + hexadecanoylamino-carnitine analog, 1.78 Å — public coordinates; measured NE2⋯analog N2 = 2.80 Å · Tyr486 OH⋯analog O13 = 2.53 Å · NE2⋯Tyr120 OH = 3.95 Å
S2 — Rufer et al., J Biol Chem 2007, PMID:17585909 — CPT2 membrane association and analog complex; companion apo 2DEB
S3 — Sequence: UniProt P23786 (human CPT2, no PDB) · NCBI Gene 1376 · rat P18886
S4 — His372: UniProt P23786 ACT_SITE ECO:0000250 — compiled onto this rat His372
S5 — Kinetics: BRENDA EC 2.3.1.21 — no kcat/Km re-asserted on this page
› Backbones and ligand poses are taken directly from the listed PDB entries,
superposed into one common frame. Where no crystalline state exists for a step
(e.g., CoA, palmitoyl-CoA, free carnitine, proton/nucleophile flight, product release), the pose is drawn
schematically and labeled as such in the narration. BUJ is an amide analog, not the physiological ester.