title: Complex coordinated extracellular metabolism: Acid phosphatases activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose.
abstract: Complex metabolism is thought to occur exclusively in the crowded intracellular environment. Here we report that diluted enzymes from lysed human leukocytes produce extracellular energy. Our findings involve two pathways: the purine nucleotide catabolic pathway and the pentose phosphate pathway, which function together to generate energy as NADPH. Glucose6P fuel for NADPH production is generated from structural ribose of purine ribonucleoside monophosphates, ADP, and ADP-ribose. NADPH drives glutathione reductase to reduce an oxidized glutathione disulfide-glutathione redox couple. Acid phosphatases initiate ribose5P salvage from purine ribonucleoside monophosphates, and transaldolase controls the direction of carbon chain flow through the nonoxidative branch of the pentose phosphate pathway. These metabolic control points are regulated by pH. Biologically, this energy conserving metabolism could function in perturbed extracellular spaces.
authors.affiliation: Emeritus, Department of Internal Medicine, Division of Infectious Diseases, University of Utah Health Science Center, Salt Lake City, UT, United States; VA Medical Center, Salt Lake City, UT, United States. Electronic address: john.hibbs@hsc.utah.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Hibbs
authors.affiliation: VA Medical Center, Salt Lake City, UT, United States.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Vavrin
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, United States; Metabolomics Core Research Facility, University of Utah School of Medicine, Salt Lake City, UT, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Cox
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism*; D004734:Energy Metabolism; D019803:Glutathione Disulfide / Q000378:metabolism*; D005980:Glutathione Reductase; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D011685:Purine Nucleotides / Q000096:biosynthesis* / Q000378:metabolism; D012266:Ribose / Q000378:metabolism
chemical_list: D011685:Purine Nucleotides; D009249:NADP; D012266:Ribose; D005980:Glutathione Reductase; D000135:Acid Phosphatase; D019803:Glutathione Disulfide
keywords: Extracellular metabolism; Glutathione reductase; Human leukocytes; Leukocyte and human prostate acid phosphatases; Redox regulation; Transaldolase