Introductory Lecture: Vitamin C Vitamins and Minerals By Fouad J Ismael
COMMON REPRESENTATION OF VITAMIN C STRUCTURE
Vitamin C is also called ascorbic acid. Below pH 4 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
and the hydroxy-lysine, that form the cross links in collagen. 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.
Fe(3+) + Vitamin C Fe(2+) + DHA 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).
O2- H2O2 Ascorbate + Fe3+ Dehydroascorbate + Fe2 Fe2+ + O2 Fe3+ + O2- Superoxide dismutase 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+) + O2 Fe(3+) + O2- SOD O2- + 2 H+ H2O2 Reduced iron, formed by vitamin C, acts upon oxygen to form the superoxide ion. SOD O2- + 2 H+ 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!!!
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, 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, -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.