Introductory Lecture:
Vitamin C
Vitamins and Minerals
Sept 3, 2014
Dr. Garry Handelman
COMMON REPRESENTATION OF
VITAMIN C STRUCTURE
Vitamin C is also called ascorbic acid. Below pH
4.5, vitamin C has all its protons (form on the
left), but at pH 7.4, it has a negative charge
(form on the right).
By convention, we use the form on the left.
Form at acidic pH
Form at body pH
PATHWAY OF
VITAMIN C
BIOSYNTHESIS:
Primates lack
the enzyme marked
with the ARROW.
Missing
enyzme
Collagen fibrils held together by cross-links
Vitamin C is required
to form both the
hydroxy-proline,
and the hydroxy-lysine,
that form the cross
links in collagen.
Iron is also needed,
notice that ascorbate
restores Fe(2+).
Vitamin C is an ELECTRON DONOR = REDUCING AGENT.
The electrons are donated to Fe3+ and Cu2+.
It can recycled (in part) by a pathway that uses
glutathione (GSH). A portion of vitamin C can
be returned to the active form..
CARNITINE SYNTHESIS REQUIRES VITAMIN C
But there is also a lot of carnitine in the normal diet.
NOREPINEPHRINE SYNTHESIS REQUIRES VITC
Vitamin C also keeps Cu in the 1+ oxidation state,
which is needed for norepinephrine synthesis
Vitamin C has some additional functions, that
are not as well-studied:
•Addition of amide groups to protein ends
•Tyrosine synthesis (from phenylalanine) and
catabolism
•Serotonin synthesis (from tryptophan)
•Antioxidant activity: there is some controversy
about this function, we will review.
REDUCTION OF FERRIC TO FERROUS:
Central to many actions of vitamin C
Fe2+ is a needed cofactor for many enzymes.
Dietary iron absorption is optimal with Fe2+,
which may be important for anemia prevention.
Fe(3+) + Vitamin C
Fe(2+) + DHA
The vitamin C is converted in this process to
the oxidized form, dehydroascorbate (DHA).
Ascorbate + Fe3+
Dehydroascorbate + Fe2
Fe2+ + O2
O2-
Fe3+
Superoxide
dismutase
+
O2-
H2O2
Thus, vitamin C can be a PRO-OXIDANT, although there is
little evidence that this is harmful.
BUT: under some circumstances, this PRO-OXIDANT
effect might be beneficial, as seen on the next slide.
Fe(2+) +
Fe(3+) + O2-
O2
Reduced iron, formed by vitamin C, acts upon oxygen to form
the superoxide ion.
O 2 - + 2 H+
SOD
H2O2
The enzyme superoxide dismutase (SOD), which is very
abundant in the extracellular fluid, converts the superoxide
to hydrogen peroxide, which can kill some tumor cells.
Very high-dose vitamin C is being used as a cancer therapy,
with some encouraging results. We will review this when
we discuss anti-oxidants/pro-oxidants.
VITAMIN C HAS SEVERAL METABOLITES.
SOME CLINICIANS ARE CONCERNED ABOUT
OXALIC ACID, WHICH CAN ACCUMULATE
AND FORM CRYSTALS IN THE TISSUES.
-Low levels of plasma vitamin C are often
noted in people are sick (MANY citations)
-Is the illness the RESULT of low vitamin C
intake, or is the illness the CAUSE?
-You have been assigned a paper that
discusses benefits of vitamin C in people
who were admitted to the hospital.
Most people get 40-200 mg/day of
vitamin C. But scurvy only occurs
at perhaps <5 mg/day.
Are people really completely healthy
at 20 mg/day? THIS HAS BEEN A
VERY TOUGH QUESTION!!!
Inflammation can decrease plasma vit C: effects
of Interleukin-2 treatment for malignancy
Marcus et al, AJCN, 1991
THIS IS SCURVY: SEVERE
VITAMIN C DEFICIENCY!
What does BORDERLINE
deficiency look like?
We don’t know! Defining
borderline deficiency is a
challenging problem in
micronutrient nutrition.
Assignment, for Sept 10
We have discussed several biochemical events that
require the action of vitamin C
Based on the biochemical step, what OBSERVABLE
changes would you predict, during severe vitamin C
deficiency?
In each case, explain how the lack of that biochemical
event leads to the observed deficiency symptoms.
In class next week, we will discuss how OTHER
HEALTH PROBLEMS can lead to symptoms
that overlap with vitamin C deficiency.
Papers to read, for Sept 10
-Relationship between vitamin C intake
and plasma levels
-Diagnosis of scurvy in a child: the clinical
challenge of a rare disorder
-Benefits of providing vitamin C supplements
to people in the hospital.