Link reaction: pyruvate dehydrogenase template

Pyruvate + CoA-SH + NAD⁺ → acetyl-CoA + CO₂ + NADH (PDH complex), with the E1/E2/E3 steps: TPP decarboxylation to hydroxyethyl-TPP, acetyl transfer to lipoamide and CoA, and reoxidation of dihydrolipoamide by FAD and NAD⁺.

What the template shows

• In the mitochondrial matrix the pyruvate dehydrogenase complex turns pyruvate into acetyl-CoA, CO₂ and NADH
• Overall: oxidative decarboxylation (irreversible)
• R = CoA (coenzyme A, linked through its thiol)
• acetyl-CoA
• E1: TPP decarboxylates pyruvate and hands the acetyl group to lipoamide
• TPP drawn as its thiazolium ring (R¹ = pyrimidinylmethyl, R² = CH₂CH₂O-diphosphate); R = lipoyl-lysine of E2. The acetyl group sits on S8 of the lipoyl arm
• hydroxyethyl-TPP
• acetyl-dihydrolipoamide
• E2 makes acetyl-CoA; E3 reoxidises the lipoyl arm with FAD and NAD⁺
• lipoamide (oxidised)
• Five cofactors from four vitamins: TPP (thiamine, B₁), lipoamide, CoA (pantothenate, B₅), FAD (riboflavin, B₂) and NAD⁺ (niacin, B₃).
• E1 = pyruvate dehydrogenase (TPP), E2 = dihydrolipoyl transacetylase (lipoamide arm swings between the active sites), E3 = dihydrolipoyl dehydrogenase (FAD → NAD⁺).
• Regulation: PDH kinase phosphorylates and switches off E1 (stimulated by acetyl-CoA, NADH, ATP); PDH phosphatase switches it on. Products inhibit the complex.
• The step is irreversible, so animals cannot make glucose from acetyl-CoA. Thiamine deficiency (beriberi) and arsenite (binds the dithiol of lipoamide) block it.

Drawn with 89 atoms, 5 arrows, 3 shapes – every one editable in MolDraw.

Sources

• Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 16 Textbook
• Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019 Textbook
• Voet & Voet, Biochemistry, 4th ed., Wiley 2011 Textbook