Inadequate Niacin Intake Disrupts Growth and Retinol Homeostasis Resulting in Higher Liver and Lower Serum Retinol Concentrations in Male Rats.

Background: Niacin-derived nicotinamide adenine dinucleotide is an essential cofactor for many dehydrogenase enzymes involved in vitamin A (VA) metabolism. Several countries with high prevalence of VA deficiency rely on maize, a poor source of available niacin, as a dietary staple.

Objectives: This study evaluated the interaction of dietary niacin on VA homeostasis using male Sprague-Dawley rats, aged 21 d (baseline body weight 88.

The Mutation of Arabidopsis Highlights How the Thiamin Economy Impacts the Methylerythritol 4-Phosphate Pathway.

The thiamin-requiring mutants of Arabidopsis have a storied history as a foundational model for biochemical genetics in plants and have illuminated the central role of thiamin in metabolism. Recent integrative genetic and biochemical analyses of thiamin biosynthesis and utilization imply that leaf metabolism normally operates close to thiamin-limiting conditions. Thus, the mechanisms that allocate thiamin-diphosphate (ThDP) cofactor among the diverse thiamin-dependent enzymes localized in plastids, mitochondria, peroxisomes, and the cytosol comprise an intricate thiamin economy.

Protocol for a Case-Control Study to Investigate the Association of Pellagra With Isoniazid Exposure During Tuberculosis Preventive Treatment Scale-Up in Malawi.

Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis.

Rethinking the PDH Bypass and GABA Shunt as Thiamin-Deficiency Workarounds.

The PDH bypass and the GABA shunt serve to maintain mainline metabolic fluxes during episodes of organellar thiamin diphosphate deficiency.

Elevated plasma cystathionine is associated with increased risk of mortality among patients with suspected or established coronary heart disease.

Background: Elevated circulating cystathionine levels are related to atherosclerotic cardiovascular disease, a leading cause of death globally.

Objective: We investigated whether plasma cystathionine was associated with mortality in patients with suspected or established coronary heart disease (CHD).

Methods: Data from 2 independent cohorts of patients with suspected stable angina pectoris (SAP) (3033 patients; median 10.

Plasma cystathionine and risk of acute myocardial infarction among patients with coronary heart disease: Results from two independent cohorts.

Background: Cystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI among patients with suspected and/or verified coronary heart disease (CHD).

Evidence that the metabolite repair enzyme NAD(P)HX epimerase has a moonlighting function.

NAD(P)H-hydrate epimerase (EC 5.1.99.

Suboptimal Vitamin B Intakes of Zambian Preschool Children: Evaluation of 24-Hour Dietary Recalls.

Background: Hidden hunger affects individuals who chronically consume an inadequate intake of at least 1 micronutrient and is associated with low dietary diversity. Little data are available on dietary intake or status assessment of B vitamins among preschool children in Zambia.

Objectives: The aim of this study was to assess 24-hour dietary recall records obtained from Zambian children aged 3 to 7 years for B vitamin intake in relation to adequacy and change over time in the same community.

Corrigendum: Divisions of labor in the thiamin biosynthetic pathway among organs of maize.

[This corrects the article on p. 370 in vol. 5, PMID: 25136345.

A plastidial pantoate transporter with a potential role in pantothenate synthesis.

The pantothenate (vitamin B) synthesis pathway in plants is not fully defined because the subcellular site of its ketopantoate → pantoate reduction step is unclear. However, the pathway is known to be split between cytosol, mitochondria, and potentially plastids, and inferred to involve mitochondrial or plastidial transport of ketopantoate or pantoate. No proteins that mediate these transport steps have been identified.

Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase.

Aims: The transsulfuration pathway enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase are thought to be the major source of hydrogen sulfide (HS). In this study, we assessed the role of CBS in HS biogenesis.

Results: We show that despite discouraging enzyme kinetics of alternative HS-producing reactions utilizing cysteine compared with the canonical condensation of serine and homocysteine, our simulations of substrate competitions at biologically relevant conditions suggest that cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of HS.

Metabolomic Evaluation of the Consequences of Plasma Cystathionine Elevation in Adults with Stable Angina Pectoris.

An elevated circulating cystathionine concentration, which arises in part from insufficiencies of vitamin B-6, B-12, or folate, has been shown to be associated with cardiovascular disease (CVD) risk. Hydrogen sulfide (HS) is a gasotransmitter involved in vasodilation, neuromodulation, and inflammation. Most endogenously produced HS is formed by pyridoxal phosphate (PLP)-dependent enzymes by noncanonical reactions of the transsulfuration pathway that yield HS concurrently form lanthionine and homolanthionine.

Astronaut ophthalmic syndrome.

During and after missions on the International Space Station, some astronauts experience ophthalmic changes, including choroidal folds, optic disc edema, cotton-wool spots, globe flattening, and refraction changes. Astronauts with ophthalmic issues had significantly higher plasma concentrations of metabolites that are associated with the 1-carbon metabolic pathway than those without ophthalmic issues. We hypothesized that genetic differences might explain the metabolite differences.

Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms Modify the Associations of Plasma Glycine and Serine With Risk of Acute Myocardial Infarction in Patients With Stable Angina Pectoris in WENBIT (Western Norway B Vitamin Intervention Trial).

Background: Serine and glycine interconversion and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-mediated 1-carbon transfer are the major sources of methyl groups for 1-carbon metabolism. Recently, plasma glycine and a common polymorphism in MTHFD1 have been associated with risk of acute myocardial infarction (AMI). It is, therefore, of interest to explore if these 2 pathways interact in relation to AMI.

Does Abiotic Stress Cause Functional B Vitamin Deficiency in Plants?

B vitamins are the precursors of essential metabolic cofactors but are prone to destruction under stress conditions. It is therefore a priori reasonable that stressed plants suffer B vitamin deficiencies and that certain stress symptoms are metabolic knock-on effects of these deficiencies. Given the logic of these arguments, and the existence of data to support them, it is a shock to realize that the roles of B vitamins in plant abiotic stress have had minimal attention in the literature (100-fold less than hormones) and continue to be overlooked.

Arabidopsis TH2 Encodes the Orphan Enzyme Thiamin Monophosphate Phosphatase.

To synthesize the cofactor thiamin diphosphate (ThDP), plants must first hydrolyze thiamin monophosphate (ThMP) to thiamin, but dedicated enzymes for this hydrolysis step were unknown and widely doubted to exist. The classical thiamin-requiring th2-1 mutation in Arabidopsis thaliana was shown to reduce ThDP levels by half and to increase ThMP levels 5-fold, implying that the THIAMIN REQUIRING2 (TH2) gene product could be a dedicated ThMP phosphatase. Genomic and transcriptomic data indicated that TH2 corresponds to At5g32470, encoding a HAD (haloacid dehalogenase) family phosphatase fused to a TenA (thiamin salvage) family protein.

A family of metal-dependent phosphatases implicated in metabolite damage-control.

DUF89 family proteins occur widely in both prokaryotes and eukaryotes, but their functions are unknown. Here we define three DUF89 subfamilies (I, II, and III), with subfamily II being split into stand-alone proteins and proteins fused to pantothenate kinase (PanK). We demonstrated that DUF89 proteins have metal-dependent phosphatase activity against reactive phosphoesters or their damaged forms, notably sugar phosphates (subfamilies II and III), phosphopantetheine and its S-sulfonate or sulfonate (subfamily II-PanK fusions), and nucleotides (subfamily I).

Short-Term Vitamin B-6 Restriction Does Not Affect Plasma Concentrations of Hydrogen Sulfide Biomarkers Lanthionine and Homolanthionine in Healthy Men and Women.

Background: Suboptimal vitamin B-6 status is associated with increased cardiovascular disease risk, although the mechanism is unknown. The synthesis of the vasodilator hydrogen sulfide occurs through side reactions of the transsulfuration enzymes cystathionine β-synthase and cystathionine γ-lyase, with pyridoxal 5'-phosphate as a coenzyme. Two proposed hydrogen sulfide biomarkers, lanthionine and homolanthionine, are produced concurrently.

Evidence that COG0325 proteins are involved in PLP homeostasis.

Pyridoxal 5'-phosphate (PLP) is an essential cofactor for nearly 60 enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life.

Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions.

The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency.