P5P-dependent Enzymes
Pyridoxal phosphate (P5P)

Author: Gianpiero Pescarmona
Date: 06/04/2019

Description

Enymes requiring P5P in Saccharomyces cerevisiae.

P5P+dependent+enzymes+human

Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase. 2006

  • Abstract
    Human cystathionine beta-synthase plays a key role in maintaining low intracellular levels of homocysteine and is unique in being a pyridoxal phosphate-dependent enzyme that is a hemeprotein. It catalyzes the beta-replacement of serine and homocysteine to generate the condensation product, cystathionine.
    In this review, we have utilized the available structural models for human cystathionine beta-synthase to conduct a structure-function analysis of a select group of pathogenic mutations described in patients with hereditary hyperhomocysteinemia.

hyperhomocysteinemia from heme or P5P deficiency?

P5P
hyperhomocysteinemia+p5p

Pyridoxal-5'-phosphate deficiency is associated with hyperhomocysteinemia regardless of antioxidant, thiamine, riboflavin, cobalamine, and folate status in critically ill patients. 2015 Yes

Heme

homocysteine+porphyria

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Preliminary report: hyperhomocysteinemia in patients with acute intermittent porphyria. 2010":https://www.ncbi.nlm.nih.gov/pubmed/20627200

  • Abstract
    Homocysteine is an intermediate of methionine metabolism, and its elevation in tissues is correlated with an increased risk for vascular diseases. We measured homocysteine in plasma of 24 patients with acute intermittent porphyria (AIP) and long-term high excretion of heme precursors. Fifteen (62.5%) presented hyperhomocysteinemia (total homocysteine in plasma >15 μmol/L). No association was found between hyperhomocysteinemia and either urinary excretion of heme precursors or clinical status. All the patients showed normal levels of vitamin B₁₂ and folic acid, but 13 (54%) presented low plasma levels of pyridoxal 5'-phosphate (PLP <15 nmol/L). Cystathionine β-synthase (CBS) catalyzes a major removal pathway of homocysteine and is dependent on both PLP and heme as cofactors. It is hypothesized that, in AIP, CBS reduced hepatic activity resulting from either a low heme status and/or consumptive depletion of PLP due to increased demand by 5-aminolevulinatesynthase hyperactivity can induce hyperhomocysteinemia.
Comments
2019-04-06T22:48:19 - Gianpiero Pescarmona

Porous Carrageenan-Derived Carbons for Efficient Ciprofloxacin Removal from Water. 2018

  • Herein, hydrochars (HCs) and porous activated carbons (ACs) derived from natural occurring polysaccharides with variable sulfate content (κ-, ι- and λ-carrageenan) were prepared and investigated in the uptake of ciprofloxacin, which is an antibiotic detected in water sources and that poses serious hazards to public health.

High-content screening for compounds that affect mtDNA-encoded protein levels in eukaryotic cells. 2010

  • Compounds that interfere with the synthesis of either mitochondrial DNA or mtDNA-encoded proteins reduce the levels of 13 proteins essential for oxidative phosphorylation, leading to a decrease in mitochondrial adenosine triphosphate (ATP) production. Toxicity caused by these compounds is seldom identified in 24- to 72-h cytotoxicity assays due to the low turnover rates of both mtDNA and mtDNA-encoded proteins. To address this problem, the authors developed a 96-well format, high-content screening (HCS) assay that measures, in eukaryotic cells, the level of Complex IV-subunit 1, an mtDNA-encoded protein synthesized on mitochondrial ribosomes, and the level of Complex V-alpha subunit, a nuclear DNA-encoded protein synthesized on cytosolic ribosomes. The effect of several antibiotics and antiretrovirals on these 2 proteins was assessed, in transformed human liver epithelial cells, 6 days after compound treatment. The results confirmed effects of drugs known to reduce mtDNA-encoded protein levels and also revealed novel information showing that several fluoroquinolones and a macrolide, josamycin, impaired expression of mtDNA-encoded proteins. The HCS assay was robust with an average Z' factor of 0.62. The assay enables large-scale screening of compounds to identify those that potentially affect mtDNA-encoded protein levels and can be implemented within a screening paradigm to minimize compound attrition.

homocysteine+aging

Homocysteine is known to be elevated in the elderly, which is possibly due to an insufficient availability of folate, B6 and/or B12.

homocysteine+estrogen

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Estrogen replacement attenuates exaggerated neointimal hyperplasia following carotid endarterectomy in rats. 2011":https://www.ncbi.nlm.nih.gov/pubmed/22262116

  • BACKGROUND To investigate whether estrogen may attenuate neointima formation in hyperhomocysteinemic rat carotid endarterectomy.
    METHODS Rats were divided into 6 groups: ovariectomized estradiol-treated homocysteine or chow; ovariectomized placebo-treated homocysteine or chow; intact placebo-treated homocysteine or chow. Chow served as controls while homocysteine served as exaggerated intimal hyperplasia. Prior to endarterectomy, rats were implanted with estradiol mini-pump or placebo, diets given 2 weeks before and after surgery. Homocysteine, estrogen, and neointimal hyperplasia were determined.
    RESULTS Homocysteine was elevated in homocysteine groups versus controls except in estradiol-treated group. Intimal hyperplasia increased in placebo-treated ovariectomized homocysteine versus intact group. Exaggerated intimal hyperplasia in placebo-treated ovariectomized homocysteine was reduced by estrogen and so was homocysteine. Estrogen replacement in ovariectomized homocysteine group reduced intimal hyperplasia to that of intact or ovariectomized controls.
    CONCLUSION Estradiol treatment in this ovariectomized hyperhomocysteinemia carotid endarterectomy and resultant attenuation of homocysteine and neointima may have relevance to the beneficial effects of estrogen on hyperplastic response.

Evidence for interactions between homocysteine and genistein: insights into stroke risk and potential treatment. 2017

  • Elevated plasma homocysteine (2-amino-4-sulfanylbutanoic acid) level is a risk factor for stroke. Moreover, it has been suggested that high levels of homocysteine in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype. In clinical studies, supplementation with genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) decreased plasma homocysteine levels considerably. Therefore, genistein could be considered as a potential drug for prevention and/or treatment of stroke. However, the mechanism of the effect of genistein on homocysteine level remains to be elucidated. In this report, direct functional interactions between homocysteine and genistein are demonstrated in in vitro experimental systems for determination of methylenetetrahydrofolate reductase (MetF) and glutathione peroxidase (GPx) activities, reconstructed with purified compounds, and in a simple in vivo system, based on measurement of growth rate of Vibrio harveyi and Bacillus subtilis cultures. Results of molecular modelling indicated that homocysteine can directly interact with genistein. Therefore, genistein-mediated decrease in plasma levels of homocysteine, and alleviation of biochemical and physiological effects of one of these compounds by another, might be ascribed to formation of homocysteine-genistein complexes in which biological activities of these molecules are abolished or alleviated.
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