BIOCHEMISTRY: VITAMINS

Lecture 1&2

Lecturer: Dr. Victor A. Mobegi, PhD

(London), DLSHTM
Contacts: Email: vatunga@uonbi.ac.ke
Mobile: +254 786 837017
Office: B57
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References
1. Thomas M. Devlin. Textbook of Biochemistry with clinical
correlations
2. Lehninger, Nelson and Cox (2008). Principles of Biochemistry,
5th Edition
3. Jeremy M Berg, John L Tymoczko, and Lubert Stryer (2002).
Biochemistry 6th Edition, New York: W H Freeman
4. John W. Baynes, Marek H. Dominiczak (2007). Medical
Biochemistry, 2nd Edition, Mosby
5. Glew R and Rosenthal M (2007). Clinical Studies in Medical
Biochemistry 3rd Ed. Oxford University Press.

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VITAMINS
• Vitamins are compounds that are essential for the health of
humans and other vertebrates but cannot be synthesized by
these animals and must therefore be obtained in the diet.
• They are micronutrients that the body cannot synthesize or
cannot adequately synthesize.
• These organic molecules are needed in small amounts in the
diets of some higher animals.
• whereas E. coli can thrive on glucose and organic salts, human
beings require at least 12 vitamins in the diet.
• Vitamins were originally thought to be “vital amines” hence
the name vitamine was given.
• The first two vitamins to be discovered were called A and B,
and were fat soluble and water soluble, respectively.
• When it was shown that vitamine A was not an amine, the “e”
was dropped and vitamin became a general term. 3
• Vitamins are activated to form coenzymes which facilitate
reactions in the body by activating enzymes.
• Deficiency of vitamins is termed avitaminosis and it can arise
due to various reasons:
1. Deficient/inadequate diet
2. Insufficient utilization
3. Malabsorption of vitamin
4. Increased requirement of the vitamin e.g. a person
recovering, during pregnancy amount of vitamin
requirement increases. Children need a lot of vitamin for
growth and development.
5. Increased excretion
• Excess of vitamins is termed hypervitaminosis. Vitamin A and
D are toxic when taken in high quantities.

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Classification of Vitamins
Vitamins are classified as fat soluble (i.e. non polar) and water
soluble (i.e. polar).

Fat soluble vitamins Water soluble vitamins

• Vitamin A (retinol), Vitamin
D (calciferol), Vitamin E (α-
tocopherol) and Vitamin K
(2-methyl-1, 4-
naphthoquinone).
• Vitamin B1 (Thiamine)
• Vitamin B2 (Riboflavin)
• Vitamin B3 (Nicotinic acid or
niacin)
• Vitamin B5 (Pantothenic acid)
• Vitamin B6 (Pyridoxine)
• Vitamin B7 (Biotin)
• Vitamin B9 (Folic acid)
• Lipoic acid
• Vitamin B12 (cobalamin)
• Vitamin C (ascorbic acid)

NB: Vitamin B4(Adenine), Vitamin B8(Inositol), Vitamin B10(pABA) and Vitamin B11
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(Salicylic acid) are no longer classified as vitamins
Vitamin A (Retinol)

• β-carotene is the precursor of vitamin A.

• Vitamin A was first isolated from fish liver oils.
• Other dietary sources include:
o liver, eggs, whole milk and milk products, butter, carrots,
mango, pumpkin, sweet potatoes, and other yellow
vegetables.

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Figure 1.1 Vitamin A1 and its precursor and derivatives
Isoprene structural units are set off by dashed red lines. Cleavage of β-
carotene yields two molecules of vitamin A1 (retinol) (b). Oxidation at C-
15 converts retinol to the aldehyde, retinal (c), and further oxidation
produces retinoic acid (d). 7
• In the intestines β-carotene is cleaved to all-trans retinal by
the enzyme dioxygenase and then all-trans retinal is
converted to all-trans retinol (A1) by the enzyme retinol
dehydrogenase.
• If Vitamin A1 is required immediately, it goes to the site of
utilization.
• If not needed for use it is stored as retinyl palmitate in the
liver. This is through esterification of retinol by palmitic acid.
• If vitamin A1 is in excess it is excreted.
Retinol (A1) Retinal Retinoic acid (which is excreted)

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Role of vitamin A

• Formation of visual pigments i.e. Rhodopsin and iodopsin.

• Retinal, a vitamin A derivative, is the pigment that initiates the
response of rod and cone cells of the retina to light, producing
a neuronal signal to the brain.
• Acting through receptor proteins in the cell nucleus, the
vitamin A derivative retinoic acid regulates gene
expression in the development of epithelial tissue, including
skin.
• Retinoic acid activates transcription of specific genes that
mediate growth and development.

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Role of vitamin A in vision
• Visual transduction begins when light falls on rhodopsin,
many thousands of molecules of which are present in each
disk of the outer segments of rod and cone cells (which are
two distinct receptor systems in retina of the eye).
• Retinal combines with the protein opsin to form rhodopsin.
• The light-absorbing pigment (chromophore) 11-cis-retinal is
covalently attached to opsin, the protein component of
rhodopsin.
• When a rhodopsin molecule is excited by visible light, the 11-
cis-retinal undergoes a series of photochemical reactions
that convert it to all-trans-retinal forcing a change in the
shape of the entire rhodopsin molecule.
• This transformation in the rod cell of the vertebrate retina
sends an electrical signal to the brain that is the basis of visual
transduction. 10
• 11-cis retinal is regenerated through enzymatic reactions so
that it can be available to combine with opsin to regenerate
rhodopsin.
A B C
All trans-retinal All trans-retinol (A1) 11-cis-retinol 11-cis-retinal

A=retinal reductase, B=retinol isomerase, C=retinal reductase

• Rhodopsin (visual purple pigment) enables vision in dim light.

• Iodopsin (violet pigment) also forms a complex with retinal
and this permits vision in very bright light.

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Deficiency

• Xerophthalmia-This is a condition where you have a very dry

eye. The cornea is affected and this can lead to blindness.
Lack of vitamin A lead to lack of mucous which makes the eye
moisturized.
• Keratomalacia
• Dry and scaly skin
• Night blindness
• Glare blindness

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Further Reading

Read on: Clinical application of optogenetics on Retinitis

pigmentosa (RP)
Reference
Reardon S. Injection of light-sensitive proteins restores blind
man's vision. Nature. 2021 May 24. doi: 10.1038/d41586-021-
01421-0. Epub ahead of print. PMID: 34035510.

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Vitamin D
• Vitamin D3 (cholecalciferol), is normally formed in the skin
from 7-dehydrocholesterol in a photochemical reaction driven
by the UV component of sunlight.
• 7-Dehydrocholesterol (provitamin D3) is photolyzed by the
ultraviolet light of sunlight to previtamin D3, which
spontaneously isomerizes to vitamin D3.
• Vitamin D3 is not itself biologically active, but it is converted
by hydroxylation reactions in the liver and kidney to
calcitriol (1,25-dihydroxycholecalciferol), a hormone that
regulates calcium uptake in the intestine and calcium levels in
kidney and bone.
• Vitamin D2 (ergocalciferol) is a commercial product formed by
UV irradiation of the ergosterol of yeast. Vitamin D2 is
structurally similar to D3, with slight modification to the
side chain attached to the sterol D ring.
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• Both have the same biological effects, and D2 is commonly
added to milk and butter as a dietary supplement. Cod-liver oil is
a rich source of vitamin D.

Synthesis of vitamin D

Figure 1.2. The synthesis of vitamin D from 7-dehydrocholesterol

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Role of vitamin D
• Vitamin D plays an essential role in the control of calcium and
phosphorus metabolism and is required for proper
calcification of bones. 1, 25-dihydroxycholecalciferol is a
hormone that regulates calcium uptake in the intestine and
calcium levels in kidney and bone.
• Like steroid hormones, 1, 25-dihydroxycholecalciferol,
regulates gene expression by interacting with specific nuclear
receptor proteins to form a complex that functions as a
transcription factor.
• Calcitriol works in concert with parathyroid hormone in Ca2+
homeostasis, regulating [Ca2+ ] in the blood and the balance
between Ca2+ deposition and Ca2+ mobilization from bone.
• Acting through nuclear receptors, calcitriol activates the
synthesis of an intestinal Ca2+ binding protein essential for
uptake of dietary Ca2+ . 17
Deficiency
• Vitamin D deficiency in childhood produces rickets, a disease
characterized by inadequate calcification of cartilage and
bone.
• In adults, vitamin D deficiency leads to softening and
weakening of bones, a condition called osteomalacia.
• In women past the age of menopause and in elderly men the
production of 1,25-dihydroxyvitamin D decreases.
• Deficiency can also occur in pregnant women
• This may be a cause of the serious bone loss termed
osteoporosis , where the rate of resorption of bone by
osteoclasts exceeds that of bone formation by osteoblasts

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• Administration of synthetic 1α,25-dihydroxyvitamin D3 or a
synthetic analog, provides an effective treatment for these
persons and also for children with an inherited defect in
production of this hormone.

• Since it is 1,25-dihydroxy derivative that is essential for control

of calcium ion metabolism, human patients with damaged
kidneys often suffer severe demineralization of their bones
(renal osteodystrophy).

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Vitamin E (α-tocopherols)
• Vitamin E is the collective name for a group of closely related
lipids called tocopherols, all of which contain a substituted
aromatic ring and a long isoprenoid side chain.
• Because they are hydrophobic, tocopherols associate with cell
membranes, lipid deposits, and lipoproteins in the blood.

Figure 1.3 Structure of vitamin E

• Dietary sources: Tocopherols are found in eggs and vegetable

oils and are especially abundant in wheat germ.
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Role of vitamin E
• Tocopherols are biological antioxidants. The major function of
the tocopherols is thought to be the protection of
phospholipids of cell membranes against oxidative attack by
free radicals and organic peroxides.
• Vitamin E prevents membrane lipid peroxidation.
• It is thought to be critical to defense against oxidative injury
and to help the body combat the development of tumors and
to slow aging.

Deficiency
Vitamin E deficiency in the rabbit or rat is accompanied by
muscular degeneration (muscular dystrophy).
Sterility in rats
Fragile erythrocytes
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Vitamin K
• This is a fat-soluble vitamin which is required for normal blood
clotting (K from the German koagulation). Vitamin K1
(phylloquinone) is found in green plant leaves; a related form,
Vitamin K2 (menaquinone), is formed by bacteria living in the
vertebrate intestine.

Figure 1.4 Structure of vitamin K1 (phylloquinone)

Role of vitamin K
• Vitamin K is essential for the synthesis of prothrombin and
several other clotting factors. The vitamin K-dependent
carboxylation reaction converts glutamate, a weak chelator of
Ca2+ into γ-carboxyglutamate, a much stronger chelator. 22
• Prothrombin is thus able to bind Ca2+

In the structures of vitamin K and its epoxide, R represents a

side chain containing several isoprenoid residues.
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• Several coagulation factors (II, VII, IX, and X) require
posttranslational modification of glutamate residues to γ-
carboxyglutamate.
• The enzyme, γ-glutamyl carboxylase, requires reduced vitamin
K as a cosubstrate and converts it to an epoxide. The latter is
reduced again by vitamin K epoxide reductase, which is
inhibited by the drug warfarin.
• Dicoumarol is used clinically as an anticoagulant to prevent
thromboses in patients prone to clot formation. Dicoumarol
and such related vitamin K antagonists as warfarin also serve
as effective rat poisons.
Deficiency
• Insufficient carboxylation of glutamate in prothrombin, a
clotting protein, slows blood clotting and can lead to
hemorrhage.
• In infants this can cause hemorrhagic disease of the newborn.
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