Formation of ketone bodies by resting lymphocytes.
1. Both beta-hydroxy-beta-methylglutaryl-coenzyme A synthase and lyase activities are present in rat mesenteric lymphocytes: all of the synthase and almost all (80%) of the lyase were present in the mitochondrial compartment of the cell. 2. A high rate of acetoacetate formation was observed in mesenteric lymphocytes incubated in vitro for 60 min in the absence of added substrate; addition of pyruvate or glutamine increased the "endogenous" rate of acetoacetate formation by about 30%. 3. The rates of ketone body formation are similar to maximal rates observed for rat liver. 4. It is suggested that the high rate of endogenous acetoacetate production occurs from long chain fatty acids: this suggestion is consistent with the reported high "endogenous" rate of O2 consumption by lymphocytes. 5. Of the pyruvate metabolized via pyruvate dehydrogenase in lymphocytes, ca 50-70% could be accounted for as acetoacetate, acetate, 3-hydroxybutyrate and citrate: the fate of the remainder is not known. 6. There was a high rate of endogenous acetoacetate formation by isolated mitochondria from these cells. 7. The rate was doubled by addition of pyruvate or butyrate; it was trebled by addition of propionate, ADP or carbonyl cyanide trichloro-methoxyphenylhydrazone; but it was decreased by addition of antimycin A or glutamine. 8. It is suggested that the high rates of acetoacetate formation in these cells acts as a dynamic "buffer" system for the acetyl coenzyme A (CoA) concentration: that is, acetyl CoA is always available for fatty acid synthesis, cholesterologenesis, chain extension of fatty acids or acetylation of proteins (e.g. for covalent control of their activity) which will be demanded at different stages of the cell cycle. 9. This is another example of branch-point sensitivity in control in cells with the potential for rapid cell division.
Curi
R
R
Department of Biochemistry, University of Oxford, England.
Williams
J F
JF
Newsholme
E A
EA
D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000378:metabolism; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis*; D008214:Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D007652:Oxo-Acid-Lyases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000090:Acetoacetates; D007657:Ketone Bodies; C016635:acetoacetic acid; D006904:Hydroxymethylglutaryl-CoA Synthase; D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase