Biotin regulates the genetic expression of holocarboxylase synthetase and mitochondrial carboxylases in rats.
Biotin is the cofactor of carboxylases [pyruvate (PC), propionyl-CoA (PCC), 3-methyl crotonyl-CoA and acetyl-CoA], to which it is covalently bound by the action of holocarboxylase synthetase (HCS). We have studied whether biotin also regulates their expression, as it does other, nonrelated enzymes (e.g., glucokinase, phosphoenol pyruvate carboxykinase, guanylate cyclase). For this purpose, HCS, PC and PCC mRNAs were studied in biotin-deficient rat liver, kidney, muscle and brain of biotin-deficient rats. PC- and PCC-specific activities and protein masses were also measured. The 24-h time course of HCS mRNA in deficient rats was examined after biotin supplementation. HCS mRNA was significantly reduced during vitamin deficiency. It increased in deficient rats after biotin was injected, reaching control levels 24 h after administration. These changes seem to be the first known instance in mammals of an effect of a water-soluble vitamin on a mRNA functionally related to it. In contrast, the decreased activities of the carboxylases were associated with reductions in the amounts of their enzyme proteins except in brain. However, their mRNA levels were not affected. There are no reports on these types of vitamin affecting the mRNA or protein levels of their apoenzymes or their products. This work provides evidence for biotin being a modulator of the genetic expression of the enzymes involved in its function as a cofactor. As such, it may be a useful model for probing a similar role for other water-soluble vitamins.
Rodríguez-Meléndez
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Unidad de Genética de la Nutrición of the Instituto de Investigaciones Biomédicas, UNAM and Instituto Nacional de Pediatría, México DF 04530.
Cano
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S
Méndez
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Velázquez
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A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001710:Biotin / Q000172:deficiency* / Q000494:pharmacology*; D019921:Biotinylation; D001921:Brain / Q000201:enzymology; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D011766:Pyruvate Carboxylase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D001710:Biotin; D002262:Carboxy-Lyases; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases; D011766:Pyruvate Carboxylase; D043586:Methylmalonyl-CoA Decarboxylase