All members of the ketol-acid reductoisomerase (KARI) enzyme family characterized to date have been shown to prefer the nicotinamide adenine dinucleotide phosphate hydride (NADPH) cofactor to nicotinamide adenine dinucleotide hydride (NADH). However, KARIs with the reversed cofactor preference are desirable for industrial applications, including anaerobic fermentation to produce branched-chain ...

BACKGROUND Atrial fibrosis, a common feature of atrial fibrillation, is thought to originate from the differential response of atrium versus ventricle to pathological insult. However, detailed mechanisms underlying the regional differences remain unclear. The aim of this study was to investigate the related factor(s) in mediating atrial vulnerability to fibrotic processes. METHODS AND RESULTS...

Glucose-1-(14)C and acetylglucosamine-1-(14)C were added singly and together with equal amounts of the unlabeled reciprocal to Brain Heart Infusion and used for the culture of Streptococcus pyogenes. The labeling pattern of the rhamnose, glucosamine, and muramic acid in the cell wall supported an intermediary role for acetylglucosamine in providing the C1-C6 moiety of muramic acid. Although rad...

Endotoxin was shown to depress neutrophil bactericidal activity while enhancing Nitro Blue Tetrazolium reduction and hexose monophosphate shunt activity. Separation of bactericidal action from oxidative metabolism suggests that the effect of endotoxin might involve the formation of reactive oxygen radicals such as superoxide. Chemiluminescence often accompanies metabolic activation of polymorph...

To date, efforts to switch the cofactor specificity of oxidoreductases from nicotinamide adenine dinucleotide phosphate (NADPH) to nicotinamide adenine dinucleotide (NADH) have been made on a case-by-case basis with varying degrees of success. Here we present a straightforward recipe for altering the cofactor specificity of a class of NADPH-dependent oxidoreductases, the ketol-acid reductoisome...

Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxy...

A reduced nicotinamide adenine dinucleotide (NADH)-dependent glutamate synthase has been detected and partially purified from crude extracts of Saccharomyces cerevisiae. The enzyme is specific for NADH, glutamine, and alpha-ketoglutarate (K(m) values of 2.6 muM, 1.0 mM, and 140 muM, respectively) and has a pH optimum between 7.1 and 7.7. The stoichiometry of the reaction has been determined as ...

Long-term treatment with N(omega)-nitro-l-arginine methylester (l-NAME), an NO synthase inhibitor, induces hypertension and cardiovascular injury. However, its precise mechanism is unknown. Using apoptosis signal-regulating kinase-1 (ASK1)-deficient mice, we investigated the role of ASK1 in cardiovascular injury caused by l-NAME treatment. l-NAME was orally administered to ASK1-deficient and C5...

Essential hypertensive patients show a reduced nitric oxide availability secondary to oxidative stress generation in peripheral microcirculation. Cyclooxygenase (COX) contributes to reduce nitric oxide availability. We assessed the possible vascular sources of oxidative stress, including COX-1, COX-2, and nicotinamide adenine dinucleotide phosphate oxidase, as determinants of endothelial dysfun...

A reduction in the survival of Salmonella typhimurium TA 1530 was observed when the bacteria were incubated with aflatoxin B¡,rat liver microsomes, and a reduced nicotinamide adenine dinucleotide phosphate-generating system. The lethality appeared to depend on the formation of a metabolite of aflatoxin B] by a mixed-function oxygenase system. The killing was very rapid; only 1% of the bacteria...