BCHS-4361-09-BIOTINI_39184

BCHS-4361-09-BIOTINI_39184 - BIOTINIDASE DEFICIENCY I...

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Unformatted text preview: BIOTINIDASE DEFICIENCY I Biotin is an essential water-soluble B-complex vitamin that is the coenzyme for four human carboxylases. These include three mitochondrial enzymes and one mainly cytosolic enzyme: Pyruvate carboxylase (PC) Propionyl CoA carboxylase (PCC) -methylcrotonyl CoA carboxylase ( MCC) Acetyl CoA carboxylase (ACC) BIOTINIDASE DEFICIENCY II Functions of these enzymes: PC: initial step in gluconeogenesis. PCC: involved in branched chain amino acid and odd chain fatty acid degradtion. MCC: catabolism of leucine. ACC: committed step in fatty acid biosynthesis. All are essential in key steps of metabolism. BIOTINIDASE DEFICIENCY III Biotin is attached to apocarboxylases by the action of biotin holocarboxylase synthetase to form holocarboxylase as follows: Biotin + ATP Biotinyl-5-AMP + PP i Biotinyl-5-AMP + apocarboxylase holocarboxylase + AMP Sum: Biotin + ATP + apocarboxylase holocarboxylase + AMP + PP i BIOTINIDASE DEFICIENCY IV All four carboxylases bind a molecule of CO 2 to the biotin ring, thus creating active CO 2 , which can be transferred to an acceptor as follows: 1) Enzyme-Biotin + ATP + HCO 3- Enzyme-Biotin-CO 2 + ADP + P i 2) Enzyme-Biotin-CO 2 + Acceptor Enzyme-Biotin + Acceptor-CO 2 Sum: HCO 3- + ATP + Acceptor Acceptor-CO 2 + ADP + P i The carboxyl group of biotin forms an amide bond with an -amino group of a specific lysine in the apoenzyme. BIOTINIDASE DEFICIENCY V When the holocarboxylase is proteolytically degraded, biocytin (biotinyl- -lysine) is formed. Biotinidase then cleaves the amide bond, releasing lysine (or lysine peptides) and free biotin, which can be re-utilized . Biotinidase can also help to release protein-bound biotin, a form that may be found in the diet, thereby providing free biotin. These steps constitute the biotin cycle. BIOTINIDASE DEFICIENCY VI Biotinidase deficiency can be manifested as multiple carboxylase defciency (MCD) , This disorder is distinct from inherited isolated deficiencies of each biotin-dependent carboxylase. The latter are due to structural abnormalities in the particular enzyme. Early-onset MCD is mainly due to a biotin holocarboxylase synthase deficiency. Late-onset MCD is usually accompanied by a deficiency in serum biotinidase. BIOTINIDASE DEFICIENCY (the next few slides are taken from a presentation on screening of newborns for selected diseases) Disorder of biotin recycling Biotin Water-soluble vitamin of the B complex Acts as a coenzyme in each of 4 carboxylases (pyruvate carboxylase, propionyl-coenzyme A [CoA] carboxylase, - methylcrotonyl CoA carboxylase, and acetyl-CoA carboxylase) Biotinidase deficiency Easily treated with vitamin supplementation Can have severe consequences if diagnosis is missed seizures, developmental delay, sensorineural deafness BIOTINIDASE DEFICIENCY Incidence Of more than 8.5 million newborn infants screened worldwide up to 1990, 142 affected infants have been...
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BCHS-4361-09-BIOTINI_39184 - BIOTINIDASE DEFICIENCY I...

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