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Table 4 Antioxidants: enzymatic – nonenzymatic inactivation of free radicals.

From: Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle

ENZYMATIC ANTIOXIDANTS

SUPER OXIDE DISMUTASE (SOD)

Reactions catalyzed: [O2- + SOD → H2O2 + O2]

Various isoforms: ecSOD (extracellular); Mn-SOD (mitochondrial); Cu/Zn-SOD (intracellular)

CATALASE – Location: peroxisome.

Reaction catalyzed: [2 H2O2 + catalase → 2 H2O + O2]

GLUTATHIONE PEROXIDASE – Location: mitochondrion, cytosol, and systemic circulation.

Glutathione (GSH or glutamyl-cysteinyl-glycine tripeptide): the reduced -SH of GSH is oxidized to disulfide GSSG.

Glutathione peroxidase-catalyzed reation: [GSH + 2 H2O2 → GSSG + H2O + O2]

Glutathione reductase-catalyzed reaction: [GSSG → GSH] at the expense of [NADH → NAD+] and/or [NAD(P)H → NAD(P)+]

ENZYMATIC – NONENZYMATIC INACTIVATION OF FREE RADICALS. NITRIC OXIDE SYNTHASE Location: membrane.

Isoforms:

eNOS (endothelial): good

nNOS (neuronal): good

iNOS (inducible-inflammatory): bad

O2- and nitric oxide (NO) are consumed in this process with the creation of reactive nitrogen species (RNS).

O2- + NO → ONOO-(peroxynitrite) + tyrosine → nitrotyrosine.

Nitrotyrosine reflects redox stress and leaves a measurable footprint.

NO the good; O2• the bad; ONOO- the ugly *

NONENZYMATIC ANTIOXIDANTS

Vitamins (A, C, and E):

Thiols: Sulfhydryl (-SH)-containing molecules.

Albumin: Is an antioxidant because of it is a thiol-containing macromolecule.

Apoproteins: Ceruloplasmin and transferrin. Bind copper and iron in forms, which cannot participate in the Fenton reaction.

Uric acid: Early on in the atherosclerotic process in physiologic ranges: antioxidant.

PARADOX: Late in elevated range prooxidant with loss of supporting antioxidants above and in a milieu of oxidative – redox stress within the atherosclerotic intima. In MS, T2DM and advanced vulnerable atherosclerotic plaques SOD, Catalase, and GPX are depleted. The Urate Redox Shuttle.

PARADOX: antioxidants may become prooxidant in a certain milieu.

  1. * Beckman JS and Koppenol WH [1996] Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271(5 Part 1): C1424–C1437