NAD Deficiency, Congenital Malformations, and Niacin Supplementation

Shi, Hongjun; Enriquez, Annabelle; Rapadas, Melissa; Martin, Ella M M A; Wang, Roni; Moreau, Julie; Lim, Chai K.; Szot, Justin O.; Ip, Eddie; Hughes, James; Sugimoto, Kotaro; Humphreys, David T.; McInerney-Leo, Aideen; Leo, Paul; Maghzal, Ghassan J.; Halliday, Jake; Smith, Janine; Colley, Alison; Mark, Paul R.; Collins, Felicity; Sillence, David; Winlaw, David S.; Ho, Joshua Wk; Guillemin, Gilles J.; Brown, Matthew A.; Kikuchi, Kazu; Thomas, Paul Q.; Stocker, Roland; Giannoulatou, Eleni; Chapman, Gavin; Duncan, Emma L.; Sparrow, Duncan B.; Dunwoodie, Sally L.

doi:10.1056/nejmoa1616361

Cited by 193 publications

(269 citation statements)

References 33 publications

Supporting

Mentioning

234

Contrasting

Unclassified

Order By: Relevance

“…Zinc and vitamin D also contribute to placental development and function. Throughout gestation iron, folate, zinc, niacin, and vitamins B 6 and A support the organogenesis and development of the fetal central nervous system, while iodine is important in early brain development . A recent study demonstrated that mitochondrial efficiency was greater for women receiving MMS compared with IFA .…”

Section: The Role Of Micronutrients In Pregnancymentioning

confidence: 99%

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low‐ and middle‐income countries

Bourassa

Osendarp

Adu‐Afarwuah

et al. 2019

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Inadequate micronutrient intakes are relatively common in low‐ and middle‐income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost‐effectiveness of MMS compared with IFA. Recent meta‐analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual‐participant data meta‐analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost‐effective method to reduce the risk of adverse birth outcomes.

show abstract

Section: The Role Of Micronutrients In Pregnancymentioning

confidence: 99%

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low‐ and middle‐income countries

Bourassa

Osendarp

Adu‐Afarwuah

et al. 2019

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…KYNU is a pyridoxal‐5′‐phosphate (pyridoxal‐P)‐dependent enzyme that catalyses the cleavage of L‐kynurenine and L‐3‐hydroxykynurenine into anthranilic and 3‐hydroxyanthranilic acids, respectively. Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway …”

Section: Introductionmentioning

confidence: 99%

“…Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway. 5 Kynureninase was associated with tryptophan utilization and metabolic diseases. It has been reported that KYNU is associated with metabolic neurological, 6 cardiac 7 and renal disease.…”

Section: Introductionmentioning

confidence: 99%

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Liu

Feng

Lai

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Breast cancer is the most common malignancy among women worldwide. Kynureninase (KYNU) located in 2q22.2, which was associated with tryptophan utilization and metabolic diseases including cardiac, renal and limb defects syndrome 2. However, the role of KYNU in breast cancer (BC) development remains unclear. The expression of KYNU was examined by immunohistochemistry (IHC) in 137 primary BC tissues, and the correlation of KYNU expression with clinical pathological characteristics and the biomarkers (ER, PR, HER2, E‐cad and Ki‐67) was analysed. The role of KYNU in cancer cell proliferation, tumour growth and development was evaluated by MTT assay, soft agar colony formation assay and xenograft mouse models. Among 137 primary BC tissues, 46.7% (64/137) had high KYNU expression (IHC scores >4) while 53.3% (73/137) had low KYNU expression (IHC scores ≤4). The expression of KYNU was positively correlated with the expressions of ER (P = .002), PR (P = .007) and E‐cad (P = .03), while negatively associated with tumour grade (P = .008), tumour stage (P < .001) and the expressions of HER2 (P = .04) and Ki‐67 (P = .019). Overexpression of KYNU significantly inhibited cell proliferation in cell culture, colony formation in soft agar and xenograft BC development in NOD/SCID mice. Kynureninase suppresses BC cell proliferation, tumour growth and development. Kynureninase may function as a tumour suppressor in BC.

show abstract

“…The importance of the source of NAD precursors extends to clinically relevant human biochemistry, where specific defects in NAD synthesis pathways are linked to birth defects. 20 The structure of NAD(H) includes a nicotinamide moiety joined to adenosine diphosphate by a ribose nucleotide, while NADP(H) includes an additional phosphate attached to C2 of the ribose ring, adjacent to the adenine moiety (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

Stable isotope labeling by essential nutrients in cell culture (SILEC) for accurate measurement of nicotinamide adenine dinucleotide metabolism

Frederick

Trefely

Buas

et al. 2017

Analyst

View full text Add to dashboard Cite

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are conserved metabolic cofactors that mediate reduction-oxidation (redox) reactions throughout all domains of life. The diversity of synthetic routes and cellular processes involving the transfer of reducing equivalents to and from these cofactors makes the accurate quantitation and metabolic tracing of NAD(H) and NADP(H) of broad interest. However, current analytical techniques typically rely on standard curves that do not incorporate confounding effects of the sample matrix. We utilized the essential requirement of niacin and tryptophan for NAD synthesis in mammalian cells to devise a stable isotope labeling by essential nutrients in cell culture (SILEC) method for efficient labeling of intracellular NAD(H) and NADP(H) pools. Coupling this approach with detection by liquid chromatography-high resolution mass spectrometry (LC-HRMS), we demonstrate the utility of incorporating a [13C315N1]-nicotinamide moiety into a library of NAD-derived metabolites for use as internal standards in matrixed samples. Using a two-label system incorporating [13C315N1]-nicotinamide and [13C11]-tryptophan, we quantify the relative contribution of salvage and de novo NAD synthesis, respectively, in S. cerevisiae and HepG2 human hepatocellular carcinoma cells under basal conditions. As a further proof-of-principle, we demonstrate an improvement in the linear range for quantification of NAD and apply this method to analysis of NAD(H) in mouse liver. This method demonstrates the generalizability of SILEC, and provides a simple method for generating a library of stable isotope labeled internal standards for quantifying and tracing the metabolism of cellular and tissue NAD(H) and NADP(H).

show abstract

NAD Deficiency, Congenital Malformations, and Niacin Supplementation

Abstract: Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice. (Funded by the National Health and Medical Research Council of Australia and others.).

Cited by 193 publications

References 33 publications

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low‐ and middle‐income countries

Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low‐ and middle‐income countries

A novel role of kynureninase in the growth control of breast cancer cells and its relationships with breast cancer

Stable isotope labeling by essential nutrients in cell culture (SILEC) for accurate measurement of nicotinamide adenine dinucleotide metabolism

Contact Info

Product

Resources

About