Biotin cell cycle

Biotin also has a role in regulation of the cell cycle, acting to biotinylate key nuclear proteins. 

H Biotin Coenzyme in carboxylation reactions in gluconeogenesis and fatty acid synthesis role in regulation of cell cycle Impaired fat and carbohydrate metabolism dermatitis... 

MetabolicaUy, biotin is of central importance in lipogenesis, gluconeogen-esis, and the catabolism of branched-chain (and other) amino acids. There are two well-characterized biotin-responsive inborn errors of metabolism, which are fatal if untreated holocarboxylase synthetase deficiency and biotinidase deficiency. In addition, biotin induces a number of enzymes, including glu-cokinase and other key enzymes of glycolysis. Biotinylation of histones may be important in regulation of the cell cycle. 

Biotin is the coenzyme in a small number of carboxylation reactions in mammalian metabolism and some decarboxylation and transcarboxylation reactions in bacteria. Although the biotin-dependent enzymes are cytosolic and mitochondrial, about 25% of tissue biotin is found in the nucleus, much of it bound as thioesters to histones. Biotin has two noncoenzyme functions induction of enzyme synthesis and regulation of the cell cycle. 

Zempleni J and Mock D (2001) Biotin homeostasis during the cell cycle. Nutrition Research Reviews 14, 45-63. 

Biotin is central to the metabolism of carbohydrates, amino acids, and lipids as biotin is the prosthetic group of the carboxylases. In addition to this metabolic function, biotin influences transcription in organisms ranging from bacteria to humans. Biotin exerts complex effects on cell cycle and gene transcription through epigenetic mechanisms. Nuclear biotin holocarboxylase synthetase seems to interact with other chromatin proteins to form a multiprotein gene repressor complex. 

In 1995, Hymes and Wolf discovered that biotini-dase can act as a biotinyl-transferase biocytin serves as the source of biotin, and histones are specifically biotinylated. Approximately 25% of total cellular biotinidase activity occurs in the nucleus. Zempleni and coworkers demonstrated that the abundance of biotinylated histones varies with the cell cycle, that biotinylated histones are increased approximately twofold compared to quiescent lymphocytes, and that histones are debiotinylated enzymatically in a process that is at least partially catalyzed by biotinidase. These observations suggest that biotin plays a role in regulating DNA transcription and regulation. 

Pyruvate carboxylase is the most important of the anaplerotie reactions. It exists in the mitochondria of animal cells but not in plants, and it provides a direct link between glycolysis and the TCA cycle. The enzyme is tetrameric and contains covalently bound biotin and an Mg site on each subunit. (It is examined in greater detail in our discussion of gluconeogenesis in Chapter 23.) Pyruvate carboxylase has an absolute allosteric requirement for acetyl-CoA. Thus, when acetyl-CoA levels exceed the oxaloacetate supply, allosteric activation of pyruvate carboxylase by acetyl-CoA raises oxaloacetate levels, so that the excess acetyl-CoA can enter the TCA cycle. 

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