Introductory Lecture:

Vitamin C

Vitamins and Minerals Sept 3, 2014

Dr. Garry Handelman

COMMON REPRESENTATION OFVITAMIN 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 OFVITAMIN CBIOSYNTHESIS:

Primates lackthe enzyme markedwith the ARROW.

Missing enyzme

Collagen fibrils held together by cross-links

Vitamin C is requiredto form both thehydroxy-proline,and the hydroxy-lysine,that form the crosslinks in collagen.

Iron is also needed, notice that ascorbaterestores 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 usesglutathione (GSH). A portion of vitamin C can

be returned to the active form..

CARNITINE SYNTHESIS REQUIRES VITAMIN CBut 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, thatare 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 tothe oxidized form, dehydroascorbate (DHA).

Ascorbate + Fe3+ Dehydroascorbate + Fe2

Fe2+ + O2 Fe3+ + O2-

O2- H2O2

Thus, vitamin C can be a PRO-OXIDANT, although there islittle evidence that this is harmful.

BUT: under some circumstances, this PRO-OXIDANTeffect might be beneficial, as seen on the next slide.

Superoxidedismutase

Fe(2+) + O2 Fe(3+) + O2-

Reduced iron, formed by vitamin C, acts upon oxygen to formthe superoxide ion.

O2- + 2 H+ H2O2

SOD

The enzyme superoxide dismutase (SOD), which is veryabundant 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 whenwe discuss anti-oxidants/pro-oxidants.

VITAMIN C HAS SEVERAL METABOLITES.SOME CLINICIANS ARE CONCERNED ABOUTOXALIC ACID, WHICH CAN ACCUMULATEAND 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: SEVEREVITAMIN C DEFICIENCY!

What does BORDERLINEdeficiency look like?

We don’t know! Definingborderline deficiency is achallenging problem in micronutrient nutrition.

Assignment, for Sept 10

We have discussed several biochemical events thatrequire the action of vitamin C

Based on the biochemical step, what OBSERVABLEchanges would you predict, during severe vitamin Cdeficiency?

In each case, explain how the lack of that biochemicalevent leads to the observed deficiency symptoms.

In class next week, we will discuss how OTHERHEALTH PROBLEMS can lead to symptomsthat overlap with vitamin C deficiency.

Papers to read, for Sept 10

-Relationship between vitamin C intakeand plasma levels

-Diagnosis of scurvy in a child: the clinicalchallenge of a rare disorder

-Benefits of providing vitamin C supplementsto people in the hospital.