Coenzyme Q10 (ubiquinone) biosynthesis (PDSS1/2, COQ2-COQ9)

Coenzyme Q10 (ubiquinone) biosynthesis (GO:0006744), grounded to ten completed human gene reviews. Tail: PDSS1 (Q5T2R2) + PDSS2 (Q86YH6) share PTHR12001 and form the heterotetrameric decaprenyl- diphosphate synthase (GO:0097269; complex GO:0032478). Ring commitment: COQ2 (Q96H96 PTHR11048, GO:0008412 4-HB polyprenyltransferase, inner membrane). Head-group modification (the membrane- associated "COQ synthome"/complex Q, GO:0110142): COQ6 (Q9Y2Z9 PTHR43876, GO:0106364 FAD monooxygenase), COQ5 (Q5HYK3 PTHR43591, GO:0008425 SAM C-methyltransferase), COQ4 (Q9Y3A0 PTHR12922, GO:0120539 Zn C1 decarboxylase + synthome scaffold — the catalytic role is from 2024 biochemistry, superseding the older "non-catalytic scaffold" view), COQ7 (Q99807 PTHR11237, GO:0160224 NADH-dependent di-iron C6 hydroxylase acting on the quinone DMQ — di-iron, NOT flavin), with COQ9 (O75208 PTHR21427) a non-catalytic lipid-binding protein that presents the DMQ substrate to COQ7. The two O-methylation steps (COQ3) are not covered (COQ3 is not in the dismech gene set). Assembly/activity of the synthome requires the atypical UbiB-family enzymes COQ8A (Q8NI60) and COQ8B (Q96D53), which share PTHR43851: their demonstrated activity is ATP hydrolysis (COQ8A/Coq8p explicitly LACK canonical in-trans protein-kinase activity — a NOT annotation; reconstituted COQ8B has measured ATPase activity, and its in vitro COQ3 phosphorylation is treated as non-core); they are regulatory rather than pathway-metabolite enzymes, so the annoton carries GO:0016887 as its function together with GO:0006744 as its process. CoQ10 is the electron carrier feeding the OXPHOS Complex III curated in the respiratory-chain modules. GO term ids/labels verified against the local go.db. Disorders: primary CoQ10 deficiency COQ10D1-D9 (COQ2 D1, PDSS1 D2, PDSS2 D3, COQ8A D4, COQ9 D5, COQ6 D6, COQ4 D7, COQ7 D8, COQ8B D9), variably CoQ10-responsive. Reaction order follows the substrate specificities of the GO terms used (COQ4 GO:0120539 acts on 4-hydroxy-3-methoxy-5-polyprenylbenzoate; COQ6 GO:0120538 hydroxylates the decarboxylated phenol; COQ5 GO:0008425 methylates 2-methoxy-6-polyprenyl-1,4-benzoquinol) and the in vitro metabolon reconstitution (PMID:38425362); an earlier version placed COQ5 before COQ4, which those substrate definitions contradict. Relationship to MODULE:ubiquinone_biosynthesis: that module is the generic bacterial aerobic pathway (UbiC/UbiA/UbiD-X/Ubi hydroxylases and methylases, metabolon factors UbiJ/UbiK/UbiB); this module is the human mitochondrial specialization, where COQ2 is the UbiA ortholog, COQ5 the UbiE ortholog, COQ3 the UbiG ortholog, COQ7 replaces the UbiF-type hydroxylase, COQ8A/B are UbiB-family members, and the C1 decarboxylation is performed by the Zn-enzyme COQ4 rather than UbiD/UbiX.

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