title: Functional defect in neutrophil cytosols from two patients with autosomal recessive cytochrome-positive chronic granulomatous disease.
abstract: The kinetics of activation of the respiratory burst oxidase in the cell-free oxidase-activating system have been explained by a three-stage mechanism in which the membrane-associated oxidase components M: (a) take up a cytosolic factor S to form a complex M.S that is (b) slowly converted in the second stage to a precatalytic species [M.S]*, which finally (c) takes up two more (possibly identical) cytosolic components, C alpha and C beta, to successively generate [M.S]*C alpha, a low-activity (i.e., high Km) oxidase, and finally [M.S]*C alpha C beta, the ordinary (i.e., low Km) oxidase (Babior, B.M., R. Kuver, and J.T. Curnutte. 1988. J. Biol. Chem. 263:1713-1718). Studies with the cell-free oxidase-activating system from normal neutrophils and from neutrophils obtained from two patients with type II (autosomal recessive cytochrome-positive) chronic granulomatous disease (CGD) have suggested that (a) the defective element in the cytosol from patient neutrophils is S; (b) in normal neutrophil cytosol, S is limiting with respect to M; and (c) C alpha and C beta interact cooperatively with the activated precursor complex [M.S]*. It was further speculated that S might be identical to the nonphosphorylated progenitor of the phosphorylated 48-kD proteins that are missing in certain forms of CGD, and that other forms of type II CGD besides the one described in this report remain to be discovered.
authors.affiliation: Department of Basic and Clinical Research, Scripps Clinic, La Jolla, California 92037.
authors.forename: J T
authors.initials: JT
authors.lastname: Curnutte
authors.forename: P J
authors.initials: PJ
authors.lastname: Scott
authors.forename: B M
authors.initials: BM
authors.lastname: Babior
mesh_terms: D002474:Cell-Free System; D003600:Cytosol / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation; D005808:Genes, Recessive; D006105:Granulomatous Disease, Chronic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism* / Q000502:physiology; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D013481:Superoxides / Q000096:biosynthesis*
chemical_list: D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme