Acetate thiokinase

This enzyme [EC 6.2.1.1], also referred to as acetate-CoA ligase or acetate thiokinase, catalyzes the reaction of acetate, coenzyme A, and ATP to form acetyl-CoA, AMP, and pyrophosphate. The enzyme will also utilize propanoate and propenoate as substrates. 

Reeves RE, Warren LG, Susskind B, Lo H-S (1977) An energy-conserving pyruvate-to-acetate pathway in Entamoeba histolytica. Pyruvate synthase and a new acetate thiokinase. J Biol Chem 252 726-731... 

Oberlies, G. Fuchs, G. Thauer, R.K. Acetate thiokinase and the assimilation of acetate in methanobacterium thermoautotrophicum. Arch. Microbiol., 128, 248-252 (1980)... 

Fluoroacetate, prepared commercially for rodent control, is also produced by a South African plant. After entering a cell, fluoroacetate is converted to fluoroacetyl-CoA in a reaction catalyzed by the enzyme acetate thiokinase ... 

Acetyl-CoA can be derived directly from metabolism, especially lipid degradation, or by the acetate thiokinase reaction ... 

See also Aconitase, Fluoroacetate, Citrate Synthase, Reaction Diagram, Acetate Thiokinase... 

See also Fluorocitrate, Acetate Thiokinase, Aconitase, Citrate Synthase... 

Acetate + CoASH + ATP <=> Acetyl-CoA + AMP + PPi (catalyzed by Acetate Thiokinase)... 

Roughan etal 2) compared acetate, pyruvate and malonate as potential precursors and found that acetate was about three times better than pyruvate while malonate was not used at all. Consistent with this result is the report of Kuhn elal Q) who found that acetate concentration in plant tissue is in the order of mM and that acetate thiokinase is localized in the plastld. Nevertheless, alternative substrates can not be entirely excluded at this stage. Schulze-Siebert etal (4) have reported that when chloroplasts are incubated with bicarbonate, pyruvate accumulates in the chloroplast. Furthermore Williams and Randall (5) have reported that pyruvate dehydrogenase of pea chloroplasts has an activity of 6-9 pmol/h/mg chlorophyll. It is therefore conceivable that the acetyl CoA used in the first steps of fatty acid synthesis is derived from pyruvate. 

A variety of thiokinases probably exist, but only a few of them have been identified. Acetic acid and butyryl thiokinase have been purified from a variety of sources, including yeast, liver, and muscle. These two enzymes differ in their specificity for the substrate. Acetic thiokinase catalyzes only the oxidation of propionic, acetic, and acrylic acids, but butyryl thiokinase activates fatty acids of chain lengths ranging from 4-to 12-carbon units. A third thiokinase was also discovered. It acts on fatty acid chains with 5- to 22-carbon units and is found in the microsomes. This intracellular distribution is in striking contrast with the cellular location of all other enzymes involved in fatty acid oxidation, which are all in mitochondria. The palmityl enzyme, which is active in the presence of ATP and CoA, becomes inactive when incubated in the absence of CoA therefore, it has been proposed that the active form of the enzyme involves the formation of an enzyme-CoA complex. The heart, the skeletal muscle, and the kidney also contain a thiokinase that specifically activates acetoacetic acid. Acetoacetic acid thiokinase is absent in liver this observation is significant in the pathogenesis of ketosis. 

Fatty Acid Activation. The activation of fatty acids [reaction (1)] is catalyzed by enzymes that are specific for various chain lengths. The first of these, the acetate-activating enzyme, acetic thiokinase, has... 

At this time, I was fortunate to have as collaborator Neil Madsen, who had recently come to spend a postdoctoral year in the Oxford Biochemistry Department after graduating from Carl Cori s Department in St. Louis, and who had chosen to risk possible disappointment by sharing with me the struggle with an apparently intractable problem. Neil had already succeeded in showing that acetate per se was not metabolized by extracts of our organisms but that such extracts were rich in acetate thiokinase activity and were thus able rapidly to form acetyl co-enzyme A from acetate, ATP and CoASH. However, despite all manner of tricks, we were unable to persuade such extracts either to oxidise acetate to CO2... 

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