PubMed Health⌕ Search

Biomedical subjects

Mark D Lucock

Publications and source records attributed to Mark D Lucock.

4 recordsLinked to original sources

G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population.

The functional consequences of the G80A RFC SNP on the expressed reduced folate carrier protein were evaluated by looking at the relationship between intake of folate, plasma folate and cellular stores of the vitamin. The effect on homocysteine was also examined. Homocysteine is a thiol that is known to be inversely associated with folate, and which is considered to be both thrombo- and athrogenic. At high levels, homocysteine may also interfere with nitric oxide mediated vasodilation, cause oxidative injury to, and proliferation of the vascular endothelium, and alter the elastic properties of the vascular wall, contributing to increased blood pressure. Participants (119; 52 male, 67 female) from a NSW retirement village were assessed. Independent of gender, the assimilation of folate from dietary sources into red cells showed a significant association for GG (r=0.399; p=0.022) and GA (r=0.564; p<0.0001) subjects, but not homozygous recessive (AA) individuals (r=0.223; p=0.236). The same genotype based pattern of significance was shown for the association between dietary folate and plasma folate (GG: r=0.524; p=0.002, GA: r=0.408; p=0.002). No genotype-related pattern of significance was shown for the association between dietary folate and homocysteine. When examined by gender, some differences were apparent; one-way ANOVA showed that genotype influenced diastolic blood pressure in males (p=0.019), while only females showed a significant correlation between dietary folate and blood pressure within specific genotypes (Systolic pressure GA: r=-0.372; p=0.025, carriage of A: r=0.-0.357; p=0.011. Diastolic pressure GA: r=-0.355; p=0.034, carriage of A: r=0.-0.310; p=0.029). The G80A RFC SNP had an impact on the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population.

Absorption↗

Synergy of genes and nutrients: the case of homocysteine.

PURPOSE OF REVIEW: Folic acid is now considered an important functional food component: it lowers potentially toxic homocysteine, prevents birth defects and modulates the risk of several cancers. The complexity of interactions involved, however, means we still have much to learn about the role of folate and homocysteine in both health and disease. RECENT FINDINGS: This review examines the emergence of homocysteine as a public health issue, and places this in context by exploring recent developments in the field of homocysteine as a vasculo, neuro and embryotoxic thiol. The paper also examines the homocysteine nexus in relation to mood disorders and cancer. It ends with an assessment of the issues associated with government-mandated folate fortification. SUMMARY: Folate fortification as a population measure may mask B12 deficiency, affect antiepileptic drug seizure control, and influence the genetic selection of a potentially deleterious genotype, albeit over a number of generations. It is likely that only large studies with a comprehensive battery of endpoints that fully address the complexity of nutrient-gene and gene-gene interactions will be able to answer all the necessary questions fully.

Folic Acid↗

Temporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal model.

Methionine dependence is unique to cancer cells and defined as the inability to grow in a methionine-deprived environment even if supplemented with the metabolic precursor homocysteine. Cobalamin-dependent methionine synthase (MS) catalyses the formation of methionine and tetrahydrofolate from homocysteine and methyltetrahydrofolate, thus linking the methionine and folate pathways. The apparent altered methionine metabolism in methionine-dependent cancer cells suggests a role for MS, although results to date are conflicting. We have analysed key metabolites of the MS-associated transmethylation, transsulphuration and folate pathways of the methionine-dependent MAC15A tumour model as a function of tumour progression over a 10-day period. MS activity increased 2-fold from day 1 to day 10. Cysteine, homocysteine, S-adenosylmethionine and S-adenosylhomocysteine levels in tumour cytosolic fractions decreased as a function of tumour progression. Plasma cysteine levels also decreased, whilst the distribution of folates in erythrocytes was altered, with a maximum increase in methyltetrahydrofolate observed by day 5. The increasing MS activity and decreasing cysteine levels suggest an increasing methionine requirement by the tumour, whilst the induction of enzyme activity indicates that MS is not defective in the methionine-dependent MAC15A tumour. The decrease in tumour S-adenosylmethionine and S-adenosylhomocysteine levels suggests that methionine is required for some function other than cellular methylation, e.g., incorporation into protein. Overall, the results support a theory of methionine conservation in response to tumour growth, where the methionine-dependent MAC15A tumour has a higher than normal methionine requirement.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗