Biomaterial Database

tert.-Butyl hydroperoxide metabolism and stimulation of the pentose phosphate pathway in isolated rat hepatocytes. 1986

G F Rush, and D Alberts

The metabolism of tert.-butyl hydroperoxide (TBHP) by the glutathione peroxidase/reductase system in isolated hepatocytes results in the rapid depletion of reduced glutathione and NADPH. The regeneration of NADPH can occur through the pentose phosphate pathway, but only when the pathway is stimulated, for example, by NADP+ and possibly oxidized glutathione, both of which can be elevated in hepatocytes exposed to TBHP. TBHP is a cytotoxicant and the role of NADPH and the pentose phosphate pathway in protecting hepatocytes from TBHP-induced injury is unknown. Isolated rat hepatocytes exposed to TBHP (0.5 mM) for 30 min metabolized more [1-14C]glucose to 14CO2 than control (638.2 +/- 96.2 vs 306.9 +/- 69.5 dpm/10(6) cells) whereas 14CO2 evolution from [6-14C]glucose was unchanged, indicating that TBHP increases the activity of the pentose phosphate pathway and not glycolysis. TBHP (0.25 mM) metabolism also resulted in a rapid oxidation of hepatocyte NADPH from 2.85 +/- 0.32 to 0.55 +/- 0.24 nmol/10(6) cells which rapidly returned to 3.58 +/- 0.27 nmol NADPH/10(6) cells. Inhibition of the pentose phosphate pathway with 6-aminonicotinamide (70 mg/kg; 5 hr prior to hepatocyte isolation) inhibited TBHP-stimulated 14CO2 evolution from [1-14C]glucose and decreased the rate of NADP+ reduction. Hepatocytes isolated from 6-aminonicotinamide-treated animals were more susceptible to TBHP-induced cell injury than were control hepatocytes. These data demonstrate the following: The metabolism of TBHP by isolated hepatocytes stimulated the activity of the pentose phosphate pathway; and inhibition of the pentose phosphate pathway with 6-aminonicotinamide potentiated the toxicity of TBHP to isolated rat hepatocytes. These results suggest that the regeneration of NADPH by the pentose phosphate pathway may play a significant role in protecting hepatocytes from TBHP-induced damage.

UI	MeSH Term	Description	Entries
D007770	L-Lactate Dehydrogenase	A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.	Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D009249	NADP	Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)	Coenzyme II,Nicotinamide-Adenine Dinucleotide Phosphate,Triphosphopyridine Nucleotide,NADPH,Dinucleotide Phosphate, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide Phosphate,Nucleotide, Triphosphopyridine,Phosphate, Nicotinamide-Adenine Dinucleotide
D009536	Niacinamide	An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.	Nicotinamide,Vitamin B 3,Vitamin PP,3-Pyridinecarboxamide,Enduramide,Nicobion,Nicotinsäureamid Jenapharm,Papulex,Vitamin B3,3 Pyridinecarboxamide,B 3, Vitamin,B3, Vitamin,Jenapharm, Nicotinsäureamid
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D010101	Oxygen Consumption	The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)	Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D010427	Pentose Phosphate Pathway	An oxidative decarboxylation process that converts GLUCOSE-6-PHOSPHATE to D-ribose-5-phosphate via 6-phosphogluconate. The pentose product is used in the biosynthesis of NUCLEIC ACIDS. The generated energy is stored in the form of NADPH. This pathway is prominent in tissues which are active in the synthesis of FATTY ACIDS and STEROIDS.	Hexose Monophosphate Shunt,Pentose Phosphate Shunt,Pentose Shunt,Pentosephosphate Pathway,Pentose-Phosphate Pathway,Pentosephosphate Shunt,Hexose Monophosphate Shunts,Pathway, Pentose Phosphate,Pathway, Pentose-Phosphate,Pathway, Pentosephosphate,Pathways, Pentose Phosphate,Pathways, Pentose-Phosphate,Pathways, Pentosephosphate,Pentose Phosphate Pathways,Pentose Phosphate Shunts,Pentose Shunts,Pentose-Phosphate Pathways,Pentosephosphate Pathways,Pentosephosphate Shunts,Shunt, Hexose Monophosphate,Shunt, Pentose,Shunt, Pentose Phosphate,Shunt, Pentosephosphate,Shunts, Hexose Monophosphate,Shunts, Pentose,Shunts, Pentose Phosphate,Shunts, Pentosephosphate
D010545	Peroxides	A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)	Peroxide
D005947	Glucose	A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.	Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose