Metabolism Of One-carbon Compounds Research Articles

One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin

The gerosuppressant metformin operates as an efficient inhibitor of the mTOR/S6K1 gerogenic pathway due to its ability to ultimately activate the energy-sensor AMPK. If an aging-related decline in the AMPK sensitivity to cellular stress is a crucial event for mTOR-driven aging and aging-related diseases, including cancer, unraveling new proximal causes through which AMPK activation endows its gerosuppressive effects may offer not only a better understanding of metformin function but also the likely possibility of repositioning our existing gerosuppressant drugs. Here we provide our perspective on recent findings suggesting that de novo biosynthesis of purine nucleotides, which is based on the metabolism of one-carbon compounds, is a new target for metformin's actions at the crossroads of aging and cancer.

Environmental proteomics of microbial plankton in a highly productive coastal upwelling system

Metaproteomics is one of a suite of new approaches providing insights into the activities of microorganisms in natural environments. Proteins, the final products of gene expression, indicate cellular priorities, taking into account both transcriptional and posttranscriptional control mechanisms that control adaptive responses. Here, we report the proteomic composition of the < 1.2 μm fraction of a microbial community from Oregon coast summer surface waters, detected with two-dimensional liquid chromatography coupled with electrospray tandem mass spectrometry. Spectra corresponding to proteins involved in protein folding and biosynthesis, transport, and viral capsid structure were the most frequently detected. A total of 36% of all the detected proteins were best matches to the SAR11 clade, and other abundant coastal microbial clades were also well represented, including the Roseobacter clade (17%), oligotrophic marine gammaproteobacteria group (6%), OM43 clade (1%). Viral origins were attributed to 2.5% of proteins. In contrast to oligotrophic waters, phosphate transporters were not highly detected in this nutrient-rich system. However, transporters for amino acids, taurine, polyamines and glutamine synthetase were among the most highly detected proteins, supporting predictions that carbon and nitrogen are more limiting than phosphate in this environment. Intriguingly, one of the highly detected proteins was methanol dehydrogenase originating from the OM43 clade, providing further support for recent reports that the metabolism of one-carbon compounds by these streamlined methylotrophs might be an important feature of coastal ocean biogeochemistry.

Methyl Group Metabolism in the Pancreas of Folate-Deficient Rats

Several studies have suggested that the metabolism of one-carbon compounds may have a special role in the function of the exocrine pancreas. An amino acid-defined diet was used to produce folate deficiency in a group of male rats. These rats were compared with a group of rats pair-fed the same diet supplemented with adequate folate and with a third group fed the folate-supplemented diet with ad libitum access. Pancreatic folate concentrations were already severely depleted after 4 wk of feeding the deficient diet (0.95 +/- 0.10, 5.81 +/- 0.29 and 4.58 +/- 0.30 nmol/g for the deficient, pair-fed control and ad libitum-fed control groups, respectively). The level of folate present in the pancreas of nondeficient animals was second only to that reported for liver. Urinary amylase excretion by animals in the deficient group was higher than that by the other groups (245.5 +/- 21.9, compared with 181.9 +/- 14.5 and 195.3 +/- 10.9 units/mg creatinine for the deficient, pair-fed control and ad libitum-fed control groups, respectively) after 4 wk. The ratio of S-adenosylmethionine to S-adenosylhomocysteine was 18.6 +/- 1.6 and 14.5 +/- 1.0 after 4 wk for the ad libitum-fed control and pair-fed control groups, respectively, but was significantly lower at 6.3 +/- 1.1 for the deficient group. These results indicate a profound effect of folate deficiency upon methyl group metabolism of the pancreas and suggest that this may result in decreased pancreatic function.

Isolation and characterization of Paracoccus denitrificans mutants with defects in the metabolism of one-carbon compounds.

Mutants deficient in the metabolism of one-carbon compounds have been obtained by treating Paracoccus denitrificans with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Mutants were selected without enrichment procedures by newly developed plate screening tests. The obtained mutants were characterized by their growth responses, cytochrome composition, enzyme activities, and immunogenic reaction with antisera against methanol dehydrogenase. By these criteria five mutant classes could be distinguished. Class I mutants are involved in the expression of methanol dehydrogenase. Three mutants of this class have a defect in the structural gene. A double mutant was found with defects in the expression of both methanol dehydrogenase and hydrogenase. Class II mutants have a defect in a regulatory gene involved in the regulation of both methanol dehydrogenase and methylamine dehydrogenase. Class III mutants are deficient in formaldehyde metabolism. A defect may exist in the expression of a second non-NAD-linked formaldehyde dehydrogenase which was postulated to be involved in C1 metabolism. Class IV mutants are deficient in cytochrome c. Mutants of class V have a defect in synthesis of the molybdenum cofactor essential for the function of formate dehydrogenase.

The Significance of Peroxisomes in the Metabolism of One-Carbon Compounds in Yeasts

Publisher Summary This chapter reviews the role of peroxisomes in the metabolism of methanol and methylated amines in yeasts. It provides information regarding their biogenesis and turnover. The studies on the physiology and biochemistry of methanol oxidation by methylotrophic yeasts exhibit that adaptation of these organisms to growth on methanol is associated with the proliferation of large microbodies in the cells. To evaluate the unique function and structure of the microbodies during methylotrophic growth in yeasts it is necessary to consider pertinent biochemical and physiological aspects of methanol metabolism in these organisms. Microbodies of methanol-grown yeasts show a number of characteristic properties.They appear in clusters in the cell and exist in close association with strands of endoplasmic reticulum. Evidence that the microbodies of methanol-grown yeasts contain alcohol oxidase and catalase is obtained via cell fractionation and cytochemical studies. The information on various aspects of the role of peroxisomes in the metabolism of one-carbon compounds in yeasts clearly shows that these unicellular organisms offer an almost ideal model system for the study of function, morphogenesis, and turnover of these intriguing organelles.

Metabolism of One-Carbon Compounds by Chemotrophic Anaerobes

Publisher Summary This chapter focuses on the metabolism of one-carbon (C1) compounds chemotrophic anaerobes. C1-metabolizing species possess novel physiologies that are distinctive in many ways from the autotrophic and heterotrophic microorganisms, which seemingly are more widespread in the microbial world. C1 compounds refer to any oxidizable one-carbon substrate that contains carbon-bound electrons. A C1 substrate differs noticeably from the C1 compound carbon dioxide because, in addition to being able to be reduced or assimilated, it can also be oxidized and can provide electrons for use in energy metabolism or cell synthesis. The term “chemotrophic anaerobe” refers to any obligately non-oxygen-catabolizing microbial species whose growth is solely dependent on the generation of metabolic energy from chemical substrates. The chapter examines the microbial physiology that accounts for unicarbonotrophy in anaerobes. The C1 metabolites enter anaerobic ecosystems of the biosphere either as pollutants from aerobic environments, volcanic or deep subsurface emanations, or via chemical transformation reactions performed by anaerobic microorganisms. The formation of C1 metabolites often necessitates their removal in biological elemental cycles because they can accumulate and alters normal carbon and electron flow within a cell, or becomes toxic and result in cell death.

NEUROPATHOLOGICAL CHANGES IN CHRONIC CYANIDE INTOXICATION.

THE presence of a small metabolically active pool of cyanide in the body is now well established. The conversion of cyanide to thiocyanate was first demonstrated in 18941. Although thiocyanate is the main excretory product of cyanide, it has been shown that it can also be oxidized to carbon dioxide and formate, and therefore cyanide-carbon can enter into the metabolism of one-carbon compounds. Using Na14CN, it has also been shown2 that the radiocarbon appears in the methyl groups of choline and methionine and in the ureide carbons of allantoin, and some of it also finds its way into the cyano groups of cyanocobalamin.