Nicotinamide mononucleotide (NMN) is one of the key precursors of coenzyme Ⅰ (NAD⁺). NMN exists widely in a variety of organisms, and β isomer is its active form. Studies have shown that β-NMN plays a key role in a variety of physiological and metabolic processes. As a potential active substance in anti-aging and improving degenerative and metabolic diseases, the application value of β-NMN has been deeply explored, and it is imminent to achieve large-scale production. Biosynthesis has become the preferred method to synthesize β-NMN because of its high stereoselectivity, mild reaction conditions, and fewer by-products. This paper reviews the physiological activity, chemical synthesis as well as biosynthesis of β-NMN, highlighting the metabolic pathways involved in biosynthesis. This review aims to explore the potential of improving the production strategy of β-NMN by using synthetic biology and provide a theoretical basis for the research of metabolic pathways as well as efficient production of β-NMN.
Nicotinamide Mononucleotide/metabolism* ; NAD/metabolism*

OBJECTIVE: This study aimed to investigate whether the supplementation of Verbal Fluency: Animal category test (VF) performance can improve the screening ability of Mini-Mental State Examination (MMSE) for mild cognitive impairment (MCI), dementia and their major subtypes. METHODS: Six hundred fifty-five cognitively normal (CN), 366 MCI [282 amnestic MCI (aMCI); 84 non-amnestic MCI (naMCI)] and 494 dementia [346 Alzheimer's disease (AD); and 148 non-Alzheimer's disease dementia (NAD)] individuals living in the community were included (all aged 50 years and older) in the study. RESULTS: The VF-supplemented MMSE (MMSE+VF) score had a significantly better screening ability for MCI, dementia and overall cognitive impairment (MCI plus dementia) than the MMSE raw score alone. MMSE+VF showed a significantly better ability than MMSE for both MCI subtypes, i.e., aMCI and naMCI. In the case of dementia subtypes, MMSE+VF was better than the MMSE alone for NAD screening, but not for AD screening. CONCLUSION: The results support the usefulness of VF-supplementation to improve the screening performance of MMSE for MCI and NAD.
Alzheimer Disease ; Animals ; Dementia* ; Mass Screening* ; Mild Cognitive Impairment* ; NAD

Alteration of H-and M-isozymfs of Lactic Dehydrogenase(LDH) were observed in the various tissues after exposing the rats to 50ppm and 250ppm of sulfur dioxide. These isozymes of the respective tissue were separated by Diethlaminoethyl(DEAE)-cellulose from tile tissue homogenates of brain, lung and muscle, presenting the activities by rate of reduction of nicot inamids-adenine-dinucleotide (NAD+). Pure LDH and the coenzyme NAD (NAD) were directly treated with sulfur dioxide in vitro order to find out the direct to sulfur dioxide on LDH and NAD+ and the results were as follow. 1. In the normal tissues, the H-isozyme activity was dominant in the brain and heart, and tole M-isozyme in the muscle. 2. In the lung tissue of normal rats, there was no different between tole activity of H-and M-type of LDH. 3 When rats inhale sulfur dioxide gas in concentration of 50ppm and 230ppm, it appeared that the H-type tend to be suppressed in aerobic tissues and the M-type in anaerobic tissues. 4. In the lung tissue exposed to sulfur dioxide, both the LDH activities were suppressed. 5. It seems that LDH and the coenzyme (NAD ) are not directly affected by exposing in sulfur dioxide gas.
Animals ; Brain ; Heart ; Isoenzymes ; Lung ; NAD ; Rats ; Sulfur Dioxide* ; Sulfur*

The redox biosynthesis system has important applications in green biomanufacturing of chiral compounds. Formate dehydrogenase (FDH) catalyzes the oxidation of formate into carbon dioxide, which is associated with the reduction of NAD(P)⁺ into NAD(P)H. Due to this property, FDH is used as a crucial enzyme in the redox biosynthesis system for cofactor regeneration. Nevertheless, the application of natural FDH in industrial production is hampered by low catalytic efficiency, poor stability, and inefficient coenzyme utilization. This review summarized the structural characteristics and catalytic mechanism of FDH, as well as the advances in protein engineering of FDHs toward improved enzyme activity, catalytic efficiency, stability and coenzyme preference. The applications of using FDH as a coenzyme regeneration system for green biomanufacturing of chiral compounds were summarized.
Catalysis ; Coenzymes/metabolism* ; Formate Dehydrogenases/metabolism* ; NAD/metabolism* ; Protein Engineering

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Citric Acid Cycle ; NAD/metabolism* ; Photons ; Neurons/metabolism*

Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.
Escherichia coli/genetics* ; NAD ; Succinic Acid ; Acetic Acid ; Adenosine Triphosphate

BACKGROUND/AIMS: NAD glycohydrolase (NADase) is abundantly expressed in the liver. This expression is prominent in Kupffer cells. Since it was recognized that reticulendothelial function is impaired in liver cirrhosis, we assessed how these enzyme activities were altered in patients with liver cirrhosis. METHODS: Serum samples were obtained from 61 patients with liver cirrhosis (according to the criteria of Child-Pugh 15 were classified A, 24 were classified B, and 22 were classified C) and 16 healthy subjects. NADase activities were measured fluorometrically with [adenine-14C] NAD. The reaction mixture contained [adenine-14C] NAD and enzyme (patient serum). The reaction was stopped after a 30 to 480 min incubation by the addition of 50 L of 25% trichloroacetic acid. RESULTS: Serum NADase activities in 61 patients with liver cirrhosis were significantly lower than those in healthy subjects (33+/-14 vs. 55.6+/-13 p<0.001). Serum NADase activities in severe cirrhotic patients were significantly lower than those in mild to moderate cirrhotic patients (criteria of Child-Pugh, A: 40.6+/-6.4 vs. B: 38.6+/-13 vs. C: 21.8+/-14, p<0.001). NADase activities were correlated to prothrombin time (r = 0.69), and Apo A1 (r = 0.58) that were useful in identifying high-risk subjects for severe liver disease, but not asparate aminotransferase (AST) and alanine aminotransferase (ALT). Also, NADase activities reciprocally correlated with PGAA index (r = -0.78), Child-Pugh's score (r = -0.48), and serum alpha-2-macroglobulin (r = -0.72). CONCLUSIONS: NADase activities could be used as a single diagnostic marker for liver cirrhosis in addition to the Child-Pugh's score and PGAA index.
Alanine Transaminase ; Apolipoprotein A-I ; Humans ; Kupffer Cells ; Liver Cirrhosis* ; Liver Diseases ; Liver* ; NAD* ; NAD+ Nucleosidase* ; Prothrombin Time ; Trichloroacetic Acid

The author studied the mental status of 497 patients admitted in non-psychiatric wards and 42 patients diagnosed as mental disorders by DSM-III-R criteria and admitted in three general hospitals located in Pusan city, using NADS and PSCS. The assessment were obtained from October, 1991 to March, 1992 and the results as follows: The mean±SD of Anxiety-Depression scores were 34.4±10.4 in non-psychiatric patients and 50.0±18.3 in psychiatric patients. The psychiatric group had significantly higher scores than non-psychiatric group. The mean±SD of Psychosis scores were 3.9±4.4 in non-psychiatric patients and 20.3±9.8 in psychiatric patients. The psychiatric group had significantly higher scores than non-psychiatric group. In the psychosocial factors, dissatisfaction in family atmosphere and acquaintanceship with parents (P<0.001, relatively), pessimistic in future, present and past self-images (P<0.001, relatively), and yes in previous psychiatric treatment of admission (p<0.01, relatively) had common significant relationships to Anxiety-Depression and Psychosis scores. There were correlationships between NADS scores and PSCS scores (γ=0.74), past and present self-images (γ=0.45), present and future self images (γ=0.45), past and future self-images (γ=0.34) and family atmosphere and acquaintanceship with parents (γ=0.49) The regression analysis revealed that present self-image, acquaintanceship with parents, future self-image, past self-image, and family atmosphere, in order of significance were to be descriptive or predicable variances for Anxiety-Depression status. The discriminant analysis according to Anxiety-Depression scores showed that the cases of incorrect classification were 22 for non-psychiatric patient group and 2 for psychiatric patient group.
Anxiety ; Atmosphere ; Busan ; Classification ; Depression ; Hospitals, General ; Humans ; Mental Disorders ; NAD ; Parents ; Psychology ; Psychotic Disorders

Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD⁺) metabolism. However, the functional role of NAD⁺ metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD⁺ levels affect the characteristics of glioma-driven SSEA1⁺ TICs, including clonogenic growth potential. An increase in the mitochondrial NAD⁺ levels by the overexpression of the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (NNT) significantly suppressed the sphere-forming ability and induced differentiation of TICs, suggesting a loss of the characteristics of TICs. In addition, increased SIRT3 activity and reduced lactate production, which are mainly observed in healthy and young cells, appeared following NNT-overexpressed TICs. Moreover, in vivo tumorigenic potential was substantially abolished by NNT overexpression. Conversely, the short interfering RNA-mediated knockdown of NNT facilitated the maintenance of TIC characteristics, as evidenced by the increased numbers of large tumor spheres and in vivo tumorigenic potential. Our results demonstrated that targeting the maintenance of healthy mitochondria with increased mitochondrial NAD⁺ levels and SIRT3 activity could be a promising strategy for abolishing the development of TICs as a new therapeutic approach to treating aging-associated tumors.
Glioblastoma* ; Lactic Acid ; Metabolism ; Mitochondria ; NAD ; NADP Transhydrogenases ; Phenotype ; Tics ; Up-Regulation*