Tuesday, July 3, 2007

Antioxidant role of Vitamin C

Ascorbate is an effective scavenger of all aggressive
reactive oxygen species within the aqueous environment
of the cytosol and extracellular fl uids. These
species include hydroxyl, superoxide anion and nonlipid
peroxyl radicals together with the non-radicals
singlet oxygen and hydrogen peroxide (Sies & Stahl,
1995). Ascorbate reacts with free radicals to produce
the ascorbyl radical and detoxifi ed product through
a single-electron transfer. Fig. 19.8 shows a possible
scheme in which ascorbate can be recycled during the
scavenging process.
Ascorbate is not the only antioxidant in aqueous
systems: other water-soluble antioxidants such as protein thiols and urate are also present. However,
ascorbate is the only endogenous antioxidant that effectively
protects the lipids in blood plasma (and also
low-density lipoprotein) against oxidative damage
initiated by non-lipid peroxyl radicals generated in
the aqueous phase. This is observed as a complete cessation
of lipid peroxidation when ascorbate is added
to plasma; other endogenous antioxidants, including
α-tocopherol, do not have this effect (Frei, 1991). Apparently,
ascorbate traps virtually all peroxyl radicals
generated in the aqueous phase before they can diffuse
into the lipid phase. Thus, ascorbate acts as the fi rst
and major line of antioxidant defence in the protection
of lipoidal plasma constituents and low-density
lipoprotein. In this action, ascorbate spares vitamin
E, the chain-breaking antioxidant in the lipid phase
(Doba et al., 1985).
In its role as a lipid-soluble, chain-breaking antioxidant
in biomembranes and lipoproteins (see Section
9.5), vitamin E (tocopherol, T-OH) scavenges
lipid peroxyl free radicals and itself is converted to
the tocopheroxyl radical (T-O•). Lipid peroxyl radicals,
because of their location in lipid environments,
cannot be scavenged by ascorbate anion. However, in
vitro studies using phospholipid liposomes as model
biomembranes have shown that ascorbate (AH–)
restores the antioxidant activity of vitamin E by converting
the tocopheroxyl radical back to the phenolic
tocopherol (reaction 19.7). Ascorbate works at the
lipid–water interface of membranes, very close to the
polar head groups of tocopherol.
T-O• + AH– → T-OH + A–• (19.7)
Whether vitamin C regenerates vitamin E in vivo is
debatable. Burton et al. (1990) found no evidence for
an interaction between the two vitamins in guinea
pigs and concluded that any such interaction must be
negligible in comparison with the normal turnover
of vitamin E.
As discussed above, ascorbate is an excellent antioxidant
but, paradoxically, it can also behave as a pro-oxidant
at lower concentrations (Buettner & Jurkiewicz,
1996). This crossover effect from pro-oxidant to
antioxidant is dependent on the ability of transition
metals in their reduced forms (e.g. Fe2+ and Cu+) to
catalyse the generation of free radicals. Ascorbate,
being a powerful reducing agent, maintains transition
metals in their catalytic reduced forms. At a high concentration
of ascorbate, the length of free radical chain
reactions will be small owing to ascorbate’s free radical
scavenging action. As the concentration of ascorbate is
lowered, there will come a point where its antioxidant
action is negligible but its capacity to reduce catalytic
metals is still suffi cient. At this crossover point ascorbate
switches from being an antioxidant to a prooxidant.
The antioxidant/pro-oxidant behaviour of
ascorbate has implications in the protection of plasma
LDL from oxidative modifi cation (Section 19.11.3).
The antioxidant action of vitamin C has a wide variety
of protective roles in the body. For example:
• the DNA in human sperm is protected from free
radical damage (Fraga et al., 1991);
• lung tissue is protected from free radical damage
resulting from inhalation of tobacco smoke, pollutants
and ozone;
• ocular tissue is protected from photo-oxidative
damage that can ultimately result in cataract formation;
• the high concentrations of ascorbate in neutrophils
and macrophages and its release on stimulation
protect these phagocytes and host tissue during the
respiratory burst in which reactive oxygen species
are produced to kill phagocytosed pathogens.

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