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Nicotinamide‐adenine dinucleotide (NAD) is involved in redox homeostasis and acts as a substrate for NADases, including poly(ADP‐ribose) polymerases (PARPs) that add poly(ADP‐ribose) polymers to proteins and DNA, and sirtuins that deacetylate proteins. Nicotinamide, a by‐product of NADases increases circadian period in both plants and animals. In mammals, the effect of nicotinamide on circadian period might be mediated by the PARPs and sirtuins because they directly bind to core circadian oscillator genes. We have investigated whether PARPs and sirtuins contribute to the regulation of the circadian oscillator in Arabidopsis. We found no evidence that PARPs and sirtuins regulate the circadian oscillator of Arabidopsis or are involved in the response to nicotinamide. RNA‐seq analysis indicated that PARPs regulate the expression of only a few genes, including FLOWERING LOCUS C. However, we found profound effects of reduced sirtuin 1 expression on gene expression during the day but not at night, and an embryo lethal phenotype in knockouts. Our results demonstrate that PARPs and sirtuins are not associated with NAD regulation of the circadian oscillator and that sirtuin 1 is associated with daytime regulation of gene expression. Nicotinamide can lengthen circadian period in mammals. We find that in Arabidopsis PARPs and sirtuins are not associated with nicotiniamide regulation of the circadian oscillator but sirtuin 1 is associated with daytime regulation of gene expression. This demonstrates a major difference in the regulation of the circadian oscillator by nicotinamide in plants and animals and identifies a major role for sirtuin 1 in affecting gene expression. [ABSTRACT FROM AUTHOR]

Methotrexate inhibits tetrahydrofolic acid production and influences mitochondrial oxygen uptake and activity of several enzymes in the respiratory chain reactions, which utilize nicotinamide adenine dinucleotide-linked (NAD-linked) substrates. Hyperproliferation of keratinocytes in psoriasis requires oxidative phosphorylation, in which the reduced form of nicotinamide adenine dinucleotide (NADH) is an electron donor. One hypothesis links increased cellular metabolism to the increased NADH/NAD+ ratio; as expected, the topical application of NAD+ (oxidized form of nicotinamide-adenine dinucleotide) resulted in a clinical improvement of psoriatic lesions in one study. Nevertheless, another report revealed reduced fluorescence of NADH in psoriatic plaques. The biological activity of NADH is not limited only to serving as the electron donor. It was also found to regulate gene transcription. [ABSTRACT FROM AUTHOR]

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A review of optical, chemical, and biological sensors to detect metabolic activity at the single-cell level is presented in the context of the development of lab-on-a-chip research instrumentation. The sensors reviewed include optical sensors, at both research and commercial levels, that can optically detect intracellular metabolites including adenosine triphosphate, nicotinamide-adenine dinucleotide, reduced flavin adenine dinucleotide, and other metabolites, including oxygen, carbon dioxide, and glucose. Methods to optically detect pH changes which are a general indicator of activity in extracellular space are also briefly reviewed. Performance metrics such as sensitivity, sensor size, drift, time response, and sensing range are included when available. Highly suitable optical sensor technologies for monitoring cellular metabolic activity include luminescent (fluorescent, phosphorescent, and chemiluminescent) and colorimetric optical probes. Different approaches to extracting luminescent and colorimetric information are reviewed, including benchtop techniques, fiber-optic approaches, and the use of probes encapsulated by biologically localized embedding. A brief discussion of alternate optical sensor technologies, such as surface plasmon resonance and infrared absorption spectroscopy, is also presented. [ABSTRACT FROM PUBLISHER]

Nicotinamide adenine dinucleotide (NAD) serves as an essential redox co-factor and mediator of multiple biological processes. Besides its well-established role in electron transfer reactions, NAD serves as a substrate for other biotransformations, which, at the molecular level, can be classified as protein post-translational modifications (protein deacylation, mono-, and polyADP-ribosylation) and formation of signaling molecules (e.g., cyclic ADP ribose). These biochemical reactions control many crucial biological processes, such as cellular signaling and recognition, DNA repair and epigenetic modifications, stress response, immune response, aging and senescence, and many others. However, the links between the biological effects and underlying molecular processes are often poorly understood. Moreover, NAD has recently been found to tag the 5′-ends of some cellular RNAs, but the function of these NAD-capped RNAs remains largely unrevealed. Synthetic NAD analogs are invaluable molecular tools to detect, monitor, structurally investigate, and modulate activity of NAD-related enzymes and biological processes in order to aid their deeper understanding. Here, we review the recent advances in the design and development of NAD analogs as probes for various cellular NAD-related enzymes, enzymatic inhibitors with anticancer or antimicrobial therapeutic potential, and other NAD-related chemical biology tools. We focus on research papers published within the last 10 years. [ABSTRACT FROM AUTHOR]