From owner-metabolic-reg@net.bio.net Wed Nov 10 22:00:00 1993 Path: biosci!daresbury!bioftp.unibas.ch!embl-heidelberg.de!rice From: rice@embl-heidelberg.de (Peter Rice) Newsgroups: bionet.metabolic-reg Subject: Re: TCA = Beta-OX Message-ID: <1993Nov11.173045.127365@embl-heidelberg.de> Date: 11 Nov 93 16:30:44 GMT References: Organization: EMBL, European Molecular Biology Laboratory Lines: 63 In article , eanv20@castle.ed.ac.uk (John Woods) writes: > Here's the original verision of MR's question. Thinking caps on ... > Hi. Your ingenuity please. > Three sequential reactions of fatty acid oxidation are chemically > identical to three reactions of the citric acid cycle. What is the > explanation for this textbook chestnut? Is there some chemical or > structural biological logic? > The reactions are fatty acyl CoA to 3-ketoacyl CoA and succinate > to oxaloacetate. Basically that's: > beta oxidation citric acid cyc > R--CH2--CH2--C(O)--COA -> COO--CH2--CH2--COO > R--CH==CH--C(O)--CoA -> COO--CH==CH--COO > R--CHOH--CH2--C(O)--CoA -> COO--CHOH--CH2--COO > R--C(O)--CH2--C(O)--CoA COO--C(O)--CH2--CO > I've heard some pretty impressive biochemists mock each other's > ideas about why this sequence is repeated. Is there some subterranean > chemical logic? I don't know if there is any structural congruity among > the enzymes of the parallel reactions. Worth a look, I suppose, if there > isn't a more obvious explanation. > Ideas? > Morgan Ryan / morgan@rock.concert.net I tried tracking these through SRS, but the sequence information is patchy in terms of species covered for each pathway. Swiss-Prot seems to have no homology reported between these pathways, but I didn't check all combinations with sequence searches and there are homologies to other enzymes in some cases. Homology checks could be complicated by the origins of the genes. Am I right in thinking that both beta oxidation and the citric acid cycle are mitochondrial in eukaryotes? It is not clear to me from the sequence database entries or from my metabolic pathways wall chart. Then there is the question of whether the genes themselves are nuclear or mitochondrial. A check of the human mitochondrial genome sequence shows only 4 protein coding genes: ATPase 6, cytochrome oxidase subunits 2 and 3, and cytochrome b, so does this mean the that all these genes are nuclear in human? The enzyme information, from Amos Bairoch's ENZYME database: Mitochondrial beta-oxidation Citric acid cycle EC Cofactor EC Cofactor 1.3.99.3 Flavoprotein* 1.3.5.1 Ubiquinone ** 4.2.1.17 - 4.2.1.2 - 1.1.1.36 NADP 1.1.1.37 NAD * further electron transfer by EC 1.5.5.1 to Ubiquinone ** EC 1.3.5.1 complex can be further degraded to EC 1.3.99.1 which no longer directly reacts with ubiquinone Objoke: the citric acid cycle is different because it has an extra first step - succinyl-CoA to succinate - while beta oxidation leaves toe CoA attached :-) ----------------------------------------------------------------------------- Peter Rice, EMBL | Post: Computer Group | European Molecular Internet: Peter.Rice@EMBL-Heidelberg.DE | Biology Laboratory | Postfach 10-2209 Phone: +49-6221-387247 | 69012 Heidelberg Fax: +49-6221-387306 | Germany .