Ramblings about work on subjects uninteresting to most people.


The case of the one hand clapping

Fatty acid synthesis happens alike in all organisms. Like an assembly line parts are hung onto a template until it grows to a long chain. The template is fixed to a bench, the ACP protein domain, and half a dozen enzymes are at work around it, and with recurring activity, to perform the task until the required length results. In one of the steps an acyl moiety is fused to a malonyl moiety and the chain so elongated. Imagine my surprise when I found everywhere the reaction depicted as

acyl-ACP + malonyl-ACP = 3-oxoacyl-ACP + CO2 + ACP         [3]

Twice ACP? That would be fine in mitochondria or bacteria, as there the ACP domain is on a separate protein and, well, let's just take two of them. But in animals' cytosol all enzymatic and ACP domains are on a single enzyme, the fatty acid synthase (FAS). Now, this FAS is a dimer in nature, which could account for the second ACP. Theoretically. We learn from the literature[1] that both monomers are sandwiched in a way that both ACP domains are far apart. Moreover, it is known[2] that the dimer can only contain one phosphopantethein (PPT) per dimer, and this also means, only one usable ACP domain.

Well, I would say one of the ACPs in the reaction actually is CoA in cytosol of animals but who is inclined to show it experimentally? Certainly not the pharma industry. The subject of mostly known physiology is boring, nothing wholly surprising or monetary is to expect. It's all Unsexy Science!

1. A. Witkowski, V. S. Rangan et al.: Structural organization of the multifunctional animal fatty-acid synthase. In: European journal of biochemistry / FEBS 198, Nr 3, June 1991, 571–579. PMID 2050137
2.  A. Jayakumar, M. H. Tai et al.: Human fatty acid synthase: properties and molecular cloning.'' In: ''Proceedings of the National Academy of Sciences of the United States of America'' V 92, Nr 19, September 1995, 8695–8699. PMID 7567999. PMC 41033
3. IUBMB Enzyme Nomenclature, EC Website

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