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Enzymatic and Non-enzymatic Antioxidative Effects of Folic Acid and Its Reduced Derivates

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Water Soluble Vitamins

Part of the book series: Subcellular Biochemistry ((SCBI,volume 56))

Abstract

A great part of the population appears to have insufficient folate intake, especially subgroups with higher demand, as determined through more sensitive methods and parameters currently in use. As the role of folate deficiency in congenital defects, e.g. in cardiovascular and neurodegenerative diseases, and in carcinogenesis has become better understood, folate has been recognized as having great potential to prevent these many disorders through folate supplementation or fortification for the general population. Folates are essential cofactors in the transfer and utilization of one-carbon groups in the process of DNA-biosynthesis with implications for genomic repair and stability. Folate acts indirectly to lower homocysteine levels and insures optimal functioning of the methylation cycle. Homocysteine was shown to be an independent risk factor for neurodegenerative and cardiovascular disease, which includes peripheral vascular disease, coronary artery disease, cerebrovascular disease and venous thrombosis. In fact, it was long believed that the beneficial effects of folate on vascular function and disease are related directly to the mechanism of homocysteine-diminution. Recent investigations have, however, demonstrated beneficial effects of folates unrelated to homocysteine-diminution, suggesting independent properties. One such mechanism could be free radical scavenging and antioxidant activity, as it is now recognized that free radicals play an important role in the oxidative stress leading to many diseases. It was found that folic acid and, in particular, its reduced derivates act both directly and indirectly to produce antioxidant effects. Folates interact with the endothelial enzyme NO synthase (eNOS) and, exert effects on the cofactor bioavailability of NO and thus, on peroxynitrite formation. Folate metabolism provides an interesting example of gene-environmental interaction.

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Abbreviations

Ang:

angiotensin

BH4:

tetrahydrobiopterin

CAD:

coronary artery disease

CβS:

cystathionine-β-synthase

DDPH:

2,2-diphenyl-1-picrylhydrazyl

DHF:

dihydrofolate

DHFR:

dihydrofolate reductase

ED:

endothelial dysfunction

EDHF:

endothelium-derived hyperpolarizing factor

EDRF:

endothelial derived relaxing factor

eNOS:

Endothelial NO synthase

FRAP:

ferric reducing ability of plasma

GPx:

glutathione peroxidase

Hcy:

homocysteine

HHcy:

hyperhomocysteinemia

H2O2 :

hydrogen peroxide

LDL:

low density lipoprotein

LPO:

lipid peroxidation

MDA:

malondialdehyde

MS:

methionine synthase

MTHFR:

methylenetetrahydrofolate reductase

5-MTHF:

5-methyl-tetrahydrofolate

NO:

nitric oxide

O2 − :

superoxide anion

·OH:

hydroxyl radical

ONOO− :

peroxynitrite

PG:

prostaglandin

RF:

relaxing factor

RFC-1:

reduced folate carrier-1

ROS:

radical oxygen species

SAM:

S-adenosylmethionine

SOD:

superoxide dismutase

TAC:

total antioxidant capacity

TAS:

total antioxidant status

TBARS:

2-thiobarbituric acid-reactive substances

TEAC:

trolox equivalent antioxidant capacity

THF:

tetrahydrofolate

TNFα:

tumor necrosis factor α

TXB2:

thromboxane B2

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Authors and Affiliations

  1. Heart Division, Cardiothoracic Surgery, Royal Brompton and Harefield NHS Foundation, Imperial College of Science, Technology and Medicine, Sydney Street, London, SW3 6NP, UK

    Olaf Stanger

  2. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Institute of Physiological Chemistry, Center for Physiological Medicine, Medical University of Graz, A-8010, Graz, Austria

    Willibald Wonisch

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  1. Imperial College of Science, Technology and Medicine, Royal Brompton & Harefield NHS Foundatio, Sydney Street, London, SW3 6NP, United Kingdom

    Olaf Stanger

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Stanger, O., Wonisch, W. (2012). Enzymatic and Non-enzymatic Antioxidative Effects of Folic Acid and Its Reduced Derivates. In: Stanger, O. (eds) Water Soluble Vitamins. Subcellular Biochemistry, vol 56. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2199-9_8

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