NADH AND NAD+

Thermoanaerobacterium aotearoense SCUT27 is a prominent producer of biofuels from lignocellulosic materials. To provide sufficient NAD(P)H for ethanol production, redox-related genes, including lactate dehydrogenase (ldh), redox-sensing transcriptional repressor (rex), and hydrogenase (hfsB), were knocked out. However, the growth of strain PRH (Δldh/Δrex/ΔhfsB) was suppressed due to the intracellular redox state imbalance with the increased NADH concentration. Coincidentally, when the Bcd-EtfAB (BCD) complex was overexpressed, the resulting strain PRH-B3 (Δldh/Δrex/ΔhfsB::BCD) grew rapidly and produced ethanol with a high yield...

The physiological role of dihydroorotate dehydrogenase (DHOD) enzymes is to catalyze the oxidation of dihydroorotate to orotate in pyrimidine biosynthesis. DHOD enzymes are structurally diverse existing as both soluble and membrane-associated forms. The Family 1 enzymes are soluble and act either as conventional single subunit flavin-dependent dehydrogenases known as Class 1A (DHODA) or as unusual heterodimeric enzymes known as Class 1B (DHODB). DHODBs possess two active sites separated by ∼20 Å, each with a noncovalently bound flavin cofactor...

The glycerol 3-phosphate shuttle (GPS) is composed of two different enzymes: cytosolic NAD+ -linked glycerol 3-phosphate dehydrogenase 1 (GPD1) and mitochondrial FAD-linked glycerol 3-phosphate dehydrogenase 2 (GPD2). These two enzymes work together to act as an NADH shuttle for mitochondrial bioenergetics and function as an important bridge between glucose and lipid metabolism. Since these genes were discovered in the 1960s, their abnormal expression has been described in various metabolic diseases and tumors...

Fetuses with growth restriction (FGR) have an early activation of hepatic glucose production (HGP), a hallmark of type 2 diabetes (T2D). Here we used fetal hepatic catheterization to directly measure HGP and substrate flux in an FGR sheep model. We hypothesized that FGR fetuses would have increased hepatic lactate and amino acid uptake to support increased HGP. Indeed, FGR compared to normal (CON) fetuses had increased HGP and activation of gluconeogenic genes. Unexpectedly, hepatic pyruvate output was increased while hepatic lactate and gluconeogenic amino acid uptake rates were decreased in FGR fetal liver...

Redox nanozymes have demonstrated tremendous promise in disrupting cellular homeostasis toward cancer therapy, but a dysfunctional competition of diverse activities makes it normally restricted by the complex tumor microenvironment (TME). As palladium nanocrystals can achieve the precise regulation of the enzyme-like activity by regulating exposed crystal planes, noble metal nanoalloys can enhance the enzyme-like activity by promoting electron transfer and enhanced active sites. Herein, bimetallic nanoalloys with optimized enzymatic activity were intelligently designed via the interaction between the Pd and layered double hydroxide, denoted as PdCu x @LDH...

PURPOSE: Chronic intermittent hypoxia (CIH) related arterial endothelium injury is a common cause of cardiovascular system injury. However, the mechanism still needs to be clarified. In this study, we aimed to clarify the role and mechanism of ferrostatin-1 (Fer-1) in CIH-related rat arterial endothelial cells (ROAEC) ferroptosis. METHODS: ROAEC was divided into control group, CIH group, and CIH+ Fer-1 group. Cell viability was detected by cell counting kit 8 kits (CCK8)...

Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD+ /NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes...

The administration of NAD+ precursors is a potential approach to protect against liver damage and metabolic dysfunction. However, the effectiveness of different NAD+ precursors in alleviating metabolic disorders is still poorly elucidated. The current study was performed to compare the effectiveness of four different NAD+ precursors, including nicotinic acid (NA), niacinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN) in alleviating high-glucose-induced injury to hepatocytes in a fish model, Megalobrama amblycephala ...

BACKGROUND/AIM: Circular RNAs can serve as detection biomarkers and therapeutic targets for tumors. Our study aimed to elucidate the mechanisms associated with circRNA LDLR (circLDLR) in gastric cancer (GC) proliferation and aerobic glycolysis. MATERIALS AND METHODS: Expression signatures of circLDLR, miR-449b-5p, and CHD1 were examined in GC samples using quantitative PCR. Proliferation ability of MKN-45 cells was assessed via CCK-8 and EdU assays, and cell apoptosis was measured by flow cytometry...

Phosphine (PH3 ) is an important contributor to the phosphorus cycle and is widespread in various environments. However, there are few studies on PH3 in constructed wetlands (CWs). In this study, lab-scale CWs and batch experiments were conducted to explore the characteristics and mechanisms of PH3 production in sulfur-based CWs. The results showed that the PH3 release flux of sulfur-based CWs varied from 0.86±0.04 ng·m-2 ·h-1 to 1.88±0.09 ng·m-2 ·h-1 . The dissolved PH3 was the main PH3 form in CWs and varied from 2...

The novel hetero-dinuclear complex trans,trans,trans-[PtIV (py)2 (N3 )2 (OH)(μ-OOCCH2 CH2 CONHCH2 -bpyMe)IrIII (ppy)2 ]Cl (Pt-Ir), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) (Pt-OH) and donor photodynamic Ir(III) (Ir-NH2 ) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex (Pt-OH) to generate Pt(II) species, an azidyl radical and 1 O2 . The Ir(III)* excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD+ ...

The rise in antimicrobial resistance is a global health crisis and necessitates the development of novel strategies to treat infections. For example, in 2022 tuberculosis (TB) was the second leading infectious killer after COVID-19, with multi-drug-resistant strains of TB having an ∼40% fatality rate. Targeting essential biosynthetic pathways in pathogens has proven to be successful for the development of novel antimicrobial treatments. Fatty-acid synthesis (FAS) in bacteria proceeds via the type II pathway, which is substantially different from the type I pathway utilized in animals...

Here we demonstrate the preparation of enzyme-metal biohybrids of NAD+ reductase with biocatalytically-synthesised small gold nanoparticles (NPs, <10 nm) and core-shell gold-platinum NPs for tandem catalysis. Despite the variety of methods available for NP synthesis, there remains a need for more sustainable strategies which also give precise control over the shape and size of the metal NPs for applications in catalysis, biomedical devices, and electronics. We demonstrate facile biosynthesis of spherical, highly uniform, gold NPs under mild conditions using an isolated enzyme moiety, an NAD+ reductase, to reduce metal salts while oxidising a nicotinamide-containing cofactor...

NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus pneumoniae , can serves as a robust model for exploring electron transfers in the NOX family thanks to its constitutive activity...

This detailed review disclosed the NF-κB pro-inflammatory gen's activity regulation and explored the therapeutic significance, activation, and inhibition. This study uncovers the structural intricacies of the NF-κB proteins and highlights the key role of SIRT1 in NF-kB signaling pathway regulation. Particularly the Rel Homology Domain (RHD), elucidating interactions and the regulatory mechanisms involving inhibitory proteins like IκB and p100 within the NF-κB signaling cascade. Disruption of the pathway is important in uncontrolled inflammation and immune disorders...

Anaerobic alcoholic fermentation, particularly in high-sugar environments, presents metabolic challenges for yeasts. Crabtree-positive yeasts, including Saccharomyces cerevisiae, prefer fermentation even in the presence of oxygen. These yeasts rely on internal NAD+ recycling and extracellular assimilation of its precursor, nicotinic acid (vitamin B3), rather than de novo NAD+ production. Surprisingly, nicotinic acid assimilation is poorly characterised, even in S. cerevisiae. This study elucidated the timing of nicotinic acid uptake during grape juice-like fermentation and its impact on NAD(H) levels, the NAD+/NADH ratio, and metabolites produced...

Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined. Here, we report that hepatocyte Cul3 knockout results in rapid resolution of steatosis in obese mice. However, the remarkable resistance of hepatocyte Cul3 knockout mice to developing steatosis does not lead to overall metabolic improvement but causes systemic metabolic disturbances...

Mitochondrial dysfunction represents one of the most common molecular hallmarks of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by the selective degeneration and death of motor neurons. The accumulation of misfolded proteins on and within mitochondria, as observed for SOD1 G93A mutant, correlates with a drastic reduction of mitochondrial respiration and the inhibition of metabolites exchanges, including ADP/ATP and NAD+ /NADH, across the Voltage-Dependent Anion-selective Channel 1 (VDAC1), the most abundant channel protein of the outer mitochondrial membrane...

5-Methyltetrahydrofolate (5-MTHF) is the sole active form of folate functioning in the human body and is widely used as a nutraceutical. Unlike the pollution from chemical synthesis, microbial synthesis enables green production of 5-MTHF. In this study, Escherichia coli BL21 (DE3) was selected as the host. Initially, by deleting 6-phosphofructokinase 1 and overexpressing glucose-6-phosphate 1-dehydrogenase and 6-phosphogluconate dehydrogenase, the glycolysis pathway flux decreased, while the pentose phosphate pathway flux enhanced...

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+ . NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+ . Herein, M1 M2 (M i =V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with K m-NADH (16...