What are vitamins (“vital amines”)?

 Organic compounds distinct from fats, carbohydrates and

proteins
 Natural components of foods usually present in minute
amounts
 Essential for normal physiological function
 Not synthesised in host
 Absence causes specific deficiency syndromes

Other useful terms:

Vitamer - chemically-related family of compounds with
same “vitamin activity”
Pro-vitamin – a precursor which is metabolised to the
active vitamin
 Vitamins, vitamers and pro-vitamins
Vitamin Vitamer Pro-vitamin
Vitamin A retinol -carotene
retinal -cryptoxanthin
retinoic acid
Vitamin D cholecalciferol (D3)
ergocalciferol (D2)
Vitamin E -tocopherol
-tocopherol
Vitamin K phylloquinones (K1)
menaquinones (K2)
menadione (K3)
Vitamin C ascorbic acid
dehydroascorbic acid
Vitamin B1 thiamin
Vitamin B2 riboflavin
Niacin nicotinamide
nicotinic acid
Vitamin B6 pyridoxal
pyridoxal
pyridoxamine
Folic acid Folic acid
polyglutamyl folacins
Biotin biotin
Pantothenic acid pantothenic acid
Vitamin B12 cobalamin
Lipid soluble and water soluble vitamins Trace elements

Thiamin
Niacin
Pantothenic acid Copper Iron
Vitamin A
Biotin Selenium Iodine
Vitamin D
Folate Manganese Zinc
Vitamin E Vitamin C Molybdenum Cobalt
Vitamin K Riboflavin
Vitamin B6
Vitamin B12

Essential Micronutrients
 Vitamin C
“Vitamin C is the generic descriptor for all compounds exhibiting
qualitatively the biological activity of ascorbic acid”

Chemical name: 2,3-didehydro-L-threo-

hexano-1,4-lactone
Commonly used trivial names : ascorbic
acid, L-ascorbic acid
Former name: hexuronic acid
Oxidised form: dehydroascrobic acid Reduced form

80% biopotency
cf reduced form

White crystalline powder Oxidised form

History of discovery of Vitamin C

3000BC

Ebers papyrii
 History of discovery

James Lind (Scotsman) found

1772 that oranges and lemons
prevented scurvy in sailors

Recognised that compound in

1907 diet needed to prevent scurvy

1921 First extracted from lemons

1932 Molecular structure characterised

1933 Synthesised by Haworth

and Hirst
 Metabolic functions of vitamin C

Hydroxylation is any chemical process that introduces one or

more hydroxyl groups (-OH) into a compound (or radical)
thereby oxidising it. In biochemistry, hydroxylation reactions are
often facilitated by enzymes called hydroxylases

Acts as a cofactor for hydroxylation

reactions
It is a reducing agent or electron donor for
at least 8 human enzymes
Accelerates hydroxylation reactions by
maintaining the active center of metal ions in
a reduced state for optimal activity of
enzymes
 Acts as a cofactor for hydroxylation
reactions
Eg Collagen synthesis
Collagen synthesis
Collagen has 3 interwoven chains of
glycine, proline and hydroxyproline
Hydroxyproline is crucial as the H-bonds of
its OH groups give chains stability
Hydroxylysine also required for x-links
Formation of hydroxyproline and
hydroxylysine require vitamin C as a cofactor

Proline hydroxylase Lysine hydroxylase

Proline hydroxyproline Lysine hydroxylysine

Vit C + Fe2+ Vit C + Fe2+

 Acts as a cofactor for hydroxylation
reactions
Eg Carnitine synthesis

NB. Carnitine is required to transport LCFA in to

mitochondria to provide an energy source for the cell
 Aids absorption of non-heme iron from gut

Mechanism:
Vit C converts iron to its
reduced state.
Less likely to form insoluble
complexes with phytate.
 For this to occur Vit C
needs to be present in the
stomach at the same time as
the non- heme iron containing
foods.

Source: Monsen (1989)

Can act as an antioxidant
 Antioxidant role of vitamin C

Can react with many reactive oxygen

species (ROS) and reactive nitrogen
species (RNS)
Can regenerate vitamin E

To be covered in more detail

in Antioxidant lecture
 Summary of some metabolic functions of vitamin C

Collagen
 Collagensynthesis
synthesis --skin,
skin,connective
connectivetissues,
tissues,bone,
bone,
teeth,cornea
teeth, cornea
Carnitine
 Carnitinesynthesis
synthesis --all
allcells
cells
Catecholamine
 Catecholaminesynthesis
synthesis --adrenals
adrenals
Tyrosine
 Tyrosinemetabolism
metabolism --brain
brainfunction
function(dopamine)
(dopamine)
Anti-histamine
 Anti-histaminereactions
reactions --all
allorgan
organsystems
systems
Immune
 Immunefunctions
functions --neutrophils,
neutrophils,antibodies
antibodies(IgG
(IgGand
andIgM)
IgM)
Bioavailability
 Bioavailabilityof
ofiron
iron -- gut
gut
Antioxidant
 Antioxidant --cell
cellcytosol
cytosol
 Metabolism of vitamin C

Absorption
Transport
Storage
Excretion
 Absorption of Vitamin C

 Absorption requires ENERGY and Na

 Both ascorbate and dehydroascorbate are transported across the
intestinal mucosal brush border membrane
 It is a rapid process
 Efficient 80-95% absorbed at intakes of up to 100mg per day.
 Rate of absorption decreases above 100mg/day

70% of blood ascorbate

is in plasma and RBC,
remainder in leukocytes
Circulates in free solution
and bound to albumin
Transport of vitamin C

Actively transported in to cell

by sodium dependent vitamin C
transporter (SVCT).
DHA is taken up by glucose
transporters (GLUT).
DHA usually reduced to ASC
in cell by DHA reductase.
High glucose concentrations
(eg diabetic hyperglycaemia)
can inhibit ascorbate uptake by
the cells.
Mechanism of ascorbate efflux
from cell unclear but does not
require sodium).
 Storage of vitamin C

No specific storage organ.

However some tissues have high levels.
Total body pool 1.5-5g at saturation.
Saturation occurs at intakes of approx 100-400mg/day

Tissue Ascorbic
acid
(mg/100g) Most found in liver and
adrenals 30-40 muscle because of their large
pituitary 40-50 mass
liver 10-16 Blood leucocytes diagnostic ?
heart 5-15
muscle 3-4
brain 3-15
Excretion of vitamin C

Kidney main route of excretion

Half life 10-20 days but this
decreases with increased intake
Main urinary metabolites
oxalic acid (45%)
2,3-diketogulonic acid (20%)
L-ascorbate sulphate (1%)
Untransformed ascorbate also
in urine, particularly as tissue
saturation is achieved.
 Signs of vitamin C deficiency

Symptoms can appear within 30days

Unable to
synthesise
vitamin C
Why have we lost
the ability to
make our own
vitamin C?

Mutation

www.wildmanstevebrill.com/.../Caveman.2.gif

We do not
express this
enzyme!
 Risk of deficiency

No fruit and vegetables in diet

Elderly may have low blood
levels and low body stores and
sometimes overt clinical signs.
Smokers have higher turnover
of Vitamin C
Oral contraceptive agents may
reduce plasma levels and
increase requirements
Disease conditions
(malabsorption, alcoholism,
anorexia)
 Ascorbic acid content in selected
foods (mg/100g edible portion)

Fruits Vegetables
Banana 8–16 Onion 10–15
Apple 3–30 Tomato 10–20
Mango 10–15 Egg plant 15–20
Pineapple 15–25 Radish 25
Cherry 15–30 Spinach 35–40
Papaya 39 Cabbage 30–70
Orange 30–50 Cauliflower 50–70
Grape fruit 30–70 Broccoli 80–90
Lemon 40–50 Coriander 90
Strawberry 40–70 Brussels sprout 100–120
Currant black 150– Pepper 150–200
200
Parsley 200–300
Rose hips 250–800
 Culinary effects on dietary vitamin C

Very labile - easily destroyed by oxygen, metal ions,

increased pH, heat or light
Enzymes - ascorbic acid oxidase normally inactive within
the plant cell is released when food is chopped
- phenolase (browning enzyme) reaction occurs
when polyphenols are exposed to the air - also
destroys Vitamin C
 Cooking
 Culinary effects on dietary vitamin C

Typical % losses of vitamin C

on cooking
Boiling 45%
Frying 30%
Cooked dishes 50%

(data from McCance & Widdowson 5)

 Official recommendations

Relationship between Vitamin C intake and plasma levels

1.2

Big difference
1.0
between US RDA
0.8
and UK RNI

0.6

0.4

0.2

0 20 40 60 80 100 120 140

Vit C intake mg/day

 Official recommendations
UK RNI US RDA
Based on the prevention of Based on achieving near
scurvy maximal neutrophil
40 mg/day concentration with minimal
urinary excretion
Pregnancy - add 10mg to RNI
90 mg/day for men
Lactation - add 30mg to RNI
75 mg/day for women
Children- scaled proportionately
from adult requirements Smokers -add 35mg/day

Recommended reading
 Vitamin C and cancer
Several prospective and observational studies suggest vit C
80-110mg/day) lowers risk of cancer of lung and GI tract.
Possible mechanism? Vitamin C protects genomic DNA from
oxidation

Lutsenko, E. A. et al. J. Biol. Chem. 2002;277:16895-16899

But intervention trials not positive

 Vitamin C and coronary heart disease

 Some epidemiological studies found that intake and plasma

concentrations associated with CHD risk.
 Possible mechanisms:
(1) Stimlates NO synthesis – vasodilation
(2) Helps prevent oxidation of LDL cholesterol

To be covered more in Antioxidant lecture

 Potential adverse reactions from supplements
Generally low toxicity but 10% of supplement users consume >1g/day.

Adverse effect Reason?

Systemic conditioning Rebound scurvy due to accelerated disposal or
metabolism
Kidney stones Increased urinary excretion of oxalic acid leading
to calcium oxalate crystals
Iron overload Enhance absorbtion of iron to detrimental levels

Gastro-intestinal problems Acidic load leading to abdominal cramps and

diarrhea. Unabsorbed vit C can lead to enhanced
microbial fermentation
Colon cancer mis-diagnosis False negatives in faecal occult blood test

Pro-oxidant activity May end up with ascorbate radicals

 Summary

Vitamin C is an essential water soluble compound for health

Main function is to assist hydroxylation reactions
Deficiency leads to scurvy
We cannot synthesise vitamin C so need it from diet
Main source is fruit and vegetables but affected by cooking
Optimum intake a matter of debate but US RDA is 90mg/day
Role in preventing cancer and CVD not clear
Long term use of “mega-doses” probably not a good idea!