SECTION ONE

1.0 Introduction

Vitamins are organic compounds required by the body in small amounts (micronutrients) for

metabolism, protection, maintenance of health and proper growth. They cannot be

synthesized by the body and must be obtained by outside sources like diet, rumen of bacteria

and sun (Bender and Mayes, 2003). Vitamins assist in the formation of hormones, blood

vessels, nervous system chemicals and genetic materials. Also, they generally act as catalysts,

combining with proteins to create metabolically active enzymes that are essential for life

reactions. Vitamins have different chemical nature, ranging from aldehydes, alcohols, organic

acids, their derivatives.

1.1 Types of Vitamins

Vitamins are classified according to their ability to be absorbed in fat or water which
includes

1. Fat soluble vitamins

Vitamin A (Retinol)

Vitamin D (Cholecalciferol)

Vitamin E (Tocopherol)

Vitamin K (phylloquinone)

2. Water soluble vitamins Vitamin B1 (Thiamin)

Vitamin B2 (Riboflavin)

Vitamin B3 (Niacin)

Vitamin B5 (Pantothenic Acid)

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 Vitamin B6 (Pyridoxine)

Vitamin B7 (Biotin)

Vitamin B9 (Folate)

Vitamin B12 (Cobalamin)

Vitamin C (Ascorbic Acid)

The water-soluble vitamins consist of B complex and vitamin C. Deficiencies of water-soluble

vitamins include beriberi, anemia and scurvy.

The lipid-soluble vitamins are non-polar hydrophobic compounds that can only be absorbed

efficiently when there is normal fat absorption and are transported in the blood.

According to Bender and Mayes (2003), fat-soluble vitamins are rich in aliphatic and aromatic

side chains, with less hydroxyl groups for which they are primarily non-polar and soluble only in

lipids and fats and usually requires to be transported in the body by means of chylomicrons. Fat-

soluble vitamins are involved in various biological functions such as vitamin A in vision, vitamin

D in calcium and phosphate metabolism, vitamin E as an antioxidant and vitamin K in blood

clotting. Deficiency in fat-soluble vitamins include night blindness, xerophthalmia, rickets in

young children, osteomalacia in adults, anemia of the newborn and hemorrhage of the newborn

(Bender and Mayes, 2003). The solubility of the vitamins determines their absorption, storage,

transportation and excretion.

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 SECTION TWO
2.0 Vitamin A (Retinol)

Figure 2.1 Structure of Vitamin A (Bender and Mayes, 2003)

Vitamin A is a pale-yellow primary alcohol derived from carotene existing in the forms, Retinol

(alcoholic form), Retinal (aldehyde form) and Retinoic acid (acidic form).

McGuire and Beerman (2013) explained that the primary source of vitamin A in food of animal

origin is ester, mostly retinyl palmitate, which is processed into retinol in the small intestine. The

type of retinol serves as the storage form of the vitamin and is convertible to and from retinal

aldehyde into a physically active form of retinol.

Vitamin A is obtained in liver oil, fish oil, Milk, chicken, leafy green vegetables, orange and

yellow vegetables, onions, broccoli, carrots, heavy grains and apples (Zetterstrom, 2009).

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Vitamin A is essential for growth and development, immune system maintenance and good

vision. It is essential for proper vision by incorporating retinal molecules that absorb light and

work during dim light and color differentiation (Jones, 2008). Retinal, the active vitamin A is the

required colour vision and lowlight perception molecule that incorporates the opsin protein to

form Rhodopsin. Dietary use of vitamin A as vitamin A precursors (carotenoids α and β

carotenes and β-cryptoxanthin) helps to reduce disorders such as age-related macular

degeneration (Pittas et al., 2010). Carotenoids are resistant to free radicals. The presence of

Carotenoids in diet causes an autoimmune response due to its role in the differentiation and

division of T cells mediating the conversion of these T cells to regulatory T cells and helps

reduce the risk of certain diseases such as lung cancer and diabetes indicating that vitamin A is

an important precursor to the proper functioning of the immune system as well as a vital role in

cell differentiation (Tardy et al., 2020).

Yamada (2013) stated that vitamin A is important for fertility in both men and women because it

is vital for the formation of sperm and eggs. In vitro studies have confirmed that retinoids could

inhibit the growth of certain cancer cells such as colon, breast and ovarian carcinoma.

2.1 Mechanism of Action of Vitamin A in Animals

In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins.

Retinaldehyde forms rhodopsin (in rods) and iodopsin (in cones). One cone cell contains only

one type of opsin and is sensitive to only one color. In the epithelium of the retina, all-trans-

retinol is isomerized to 11-cis-retinol and oxidized to 11-cis-retinaldehyde which reacts with a

lysine residue in opsin, to form the holoprotein rhodopsin as explained by Bender and Mayes
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(2003). The absorption of light by rhodopsin causes isomerization of the retinaldehyde from 11-

cis to all-trans, and a conformational change in opsin resulting in the release of retinaldehyde

from the protein and the initiation of a nerve impulse. There is formation of the excited form of

rhodopsin and bathorhodopsin, which occurs within picoseconds of illumination, followed by a

series of conformational changes leading to the formation of metarhodopsin II, which initiates a

guanine nucleotide amplification cascade as well as a nerve impulse followed by hydrolysis to

release all-trans-retinaldehyde and opsin (Bender and Mayes, 2003).

Vitamin A also functions in the control of cell differentiation and turnover. Retinoic acid binds

to nuclear receptors that bind to response elements of DNA and regulate the transcription of

specific genes. The retinoic acid receptors bind to the all-trans-retinoic acid and the retinoid X

receptors bind to the all-trans retinol which is then converted in the retina to 11-cis-retinal which

functions in the retina in the transduction of light into neural signals (nerve impulse to the brain)

and allows for the perception of light. 11-cis-retinal, while attached to opsin in rhodopsin is

isomerized to all-trans-retinal by light (Penniston and Tanumihardjo, 2006).

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2.2 Vitamin D (Calcitriol)

Figure 2.2.1 Structure of vitamin D (Bender and Mayes, 2003)

Vitamin D or calcitriol is a steroid hormone which carries out important role in regulating body

levels of calcium, phosphorus and in mineralization of bone. Vitamin D refers to one or more

members of a group of steroid molecules. Vitamin D can be synthesized in adequate amounts by

most mammals exposed to sufficient quantities of sunlight as its major source under most

conditions. Only when sunlight is inadequate is a dietary source required (Bender and Mayes,

2003).

Vitamin D exists in two forms, vitamin D2 and vitamin D3. The plant form of vitamin D is called

vitamin D2 or ergosterol while Vitamin D3, also known as cholecalciferol is generated in the skin

of animals when light energy is absorbed by a precursor molecule 7-dehydrocholesterol. Dietary

sources of vitamin D, includes egg yolk, fish oil and a number of plants. Vitamin D, as either D 3
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or D2, does not have significant biological activity rather, it must be metabolized within the

body to the hormonally-active form known as 1,25-dihydroxycholecalciferol and its

photochemical conversion to cholecalciferol is quite inefficient (Aranow, 2011). It has been

found that dogs and cats appear to rely on dietary intake of vitamin D more than other animals

(How et al.,1994).

2.2.1 Mechanism of Action of vitamin D in Animals

Gonzalez (2010) described that the active form of vitamin D binds to intracellular receptors

which function as transcription factors to modulate gene expression. The vitamin D receptor has

hormone-binding and DNA-binding domains and forms a complex with another intracellular

receptor, the retinoid-X receptor, which binds to DNA to either activate transcription or in some

cases, suppress transcription.

In the liver, cholecalciferol synthesized in the skin or derived from food is hydroxylated to form

the 25-hydroxyderivativecalcidiol released into the circulation bound to a vitamin D-binding

globulin which is the main storage form of the vitamin. In the kidney, calcidiol further undergoes

either 1-hydroxylation to yield the active metabolite 1,25-dihydroxyvitamin D (calcitriol) or 24-

hydroxylation to yield an inactive metabolite, 24,25-dihydroxyvitamin D (24-hydroxycalcidiol).

Calcitriol acts to reduce its own synthesis by inducing the 24-hydroxylase and repressing the 1-

hydroxylase in the kidney (Meyer et al., 2010).

The principal function of Calcitriol is to maintain the plasma calcium concentration and it

achieves this in three ways: increasing intestinal absorption of calcium, reducing excretion of

calcium (by stimulating resorption in the distal renal tubules) and mobilizing bone mineral.

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Ordinarily, the 1,25-dihydroxyvitamin D binds to endogenous vitamin D receptors, resulting in a

variety of regulatory roles including maintaining calcium balance, the regulation of parathyroid

hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of

calcium and phosphorus, increased calcium and phosphorus mobilization from bone to plasma in

order to maintain balanced levels of each in bone and the plasma respectively as described by

Meyer et al., (2010). The binding affinity of vitamin D receptor for 1,25-

dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol

(Marcinowska-Suchowierska et al., 2018).

Norman et al., (1997) reported that 1,25-dihydroxycholecalciferol also exerts effects that involve

a genomic action. The first of these that was identified involved the rapid stimulation of intestinal

calcium transport in a vitamin D replete chick, called transcaltachia. Analogs of 1,25-

dihydroxycholecalciferol with little genomic activity were comparable in function with respect to

transcaltachia. The collection of various pathways known to be regulated by 1,25-

dihydroxycholecalciferol opens up a large selection of targets for clinical application, with the

provision that functional selectivity can be achieved to match the cell-specific genomic activity.

This discovery has positively encouraged the development of 1,25-dihydroxycholecalciferol

analogs for such functions (Norman et al., 1997).

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2.3 Vitamin E

(Tocopherol)

Fig 2.3.1 Structure of Vitamin E alpha Tocopherol (Vasudevan and Vaidyanathan, 2017).

Vitamin E is a fat-soluble vitamin with several forms having alpha-tocopherol as the only form

used by the human body. Vasudevan and Vaidyanathan (2017) described the main role of vitamin

E as an antioxidant, scavenging loose electrons called “free radicals” that can damage cells. It

also enhances immune function and prevents clots from forming in heart arteries. Antioxidant

vitamins, including vitamin E, came to public attention in the 1980s when scientists began to

understand that free radical damage was involved in the early stages of artery-clogging

atherosclerosis, and might also contribute to cancer, vision loss, and a host of other chronic

conditions. The most important sources of vitamin E includes oil from soya, palm, corn,

safflower, sunflower, wheat germ and nut oils. Other sources include nuts, seeds, whole grains,

leafy green vegetables, chick peas, avocados, sweet potatoes, sweetcorn, red peppers, carrots,

parsnips, milk, eggs and cheese. Vitamin E has the ability to protect cells from free radical

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damage as well as reduce the production of free radicals in some situations. High dose of vitamin

E has been used to prevent chronic diseases (Bender and Mayes, 2003). No unique function for

vitamin E has been defined. However, it acts as a lipid-soluble antioxidant in cell membranes,

where many of its functions can be provided by synthetic antioxidants. Vitamin E is the name for

two families of compounds, the tocopherols and the tocotrienols. The different vitamers

(compounds having similar vitamin activity) have different biological functions. The most active

form is D-α-tocopherol. Vitamin E intake is usually measured in milligrams of D-α-tocopherol

equivalents. Synthetic D-α-tocopherol does not have the same biological potency as the naturally

occurring compound (Bender and Mayes, 2003). Vitamin E also helps to reduce the production of

prostaglandins such as thromboxane, which cause platelet clumping (Rizvi et al., 2014).

Vitamin E is used for treating vitamin E deficiency, which is rare, but can occur in people with

certain genetic disorders and in very low-weight premature infants. Vitamin E is also used for

many other conditions, but there is no good scientific evidence to support many of these other

uses.

2.3.1 Mechanism of action of Vitamin E in animals

Vitamin E is absorbed by micelles into chylomicrons which is transported via lipoproteins then

stored in adipose tissue and further excreted through the bile, urine and skin. Vitamin E also

serves as an antioxidant, though very unstable but easily oxidized and protect cells against

oxidative damage by free radicals, for example oxidation of the lipids in the cell membrane plays

a role in aging, sexual performance, prevention of cancer and heart disease as explained by

Pandey (2014). Vitamin E reacts with the lipid peroxide radicals formed by peroxidation of

polyunsaturated fatty acids before establishing a chain reaction. The tocopheroxyl free radical
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product is relatively unreactive and ultimately forms non-radical compounds. The tocopheroxyl

radical is reduced back to tocopherol by reaction with vitamin C from plasma. The reaction

results in monodehydroascorbate free radical and undergoes enzymic or non-enzymic reaction to

yield ascorbate and dehydroascorbate, neither of which is a free radical. The stability of the

tocopheroxyl free radical means that it can penetrate farther into cells and carry out a chain

reaction. Vitamin E like other antioxidants,may also have pro-oxidant actions especially at high

concentrations. This may explain why, though studies have shown an association between high

blood concentrations of vitamin E and a lower incidence of atherosclerosis. The effect of high

doses of vitamin E have been ineffective in most cases (Bender and Mayes, 2003).

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2.4 Vitamin K (Phylloquinone)

Figure 2.4.1

Structure of

vitamin K

(Bender and

Mayes,

2003).

Vitamin K are polymers found in food as dietary supplements. Vasudevan and Vaidyanathan

(2017) stated that the human body requires vitamin K for post-synthesis modification of certain

proteins that are required for blood coagulation (K is derived from Koagulation, a German word

for "coagulation") or for controlling binding of calcium in bones and other tissues. Vitamin K is

referred to as the blood-clotting vitamin.

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Vitamin K was discovered as a result of investigations into the cause of a bleeding disorder,

hemorrhagic (sweet clover) disease of cattle and chicken fed on a fat-free diet. The missing factor

in the diet of the chicken was vitamin K, while the cattle feed contained dicumarol, an antagonist

of the vitamin K. Antagonists of vitamin K are used to reduce blood coagulation in patients at

risk of thrombosis. The most widely used agent is warfarin.

Two compounds have the biological activity of vitamin K: phylloquinone, the normal dietary

source, found in green vegetables and menaquinone, synthesized by intestinal bacteria with

differing lengths of side-chain (menadione, menadiol and menadiol diacetate) synthetic

compounds that can be metabolized to phylloquinone. Menaquinones are absorbed to some extent

but it is not clear to what extent they are biologically active as it is possible to induce signs of

vitamin K deficiency simply by feeding a phylloquinone deficient diet without inhibiting

intestinal bacterial action. (Dowd et al., 1995).

In normal adults, dietary deficiency of vitamin K will not occur since the intestinal bacterial

synthesis is sufficient to meet the needs of the body. However, deficiency can occur in conditions

of malabsorption of lipids. This can result from obstructive jaundice, chronic pancreatitis, and

sprue. Prolonged antibiotic therapy and gastrointestinal infections with diarrhea will destroy the

bacterial flora and can also lead to vitamin K deficiency (Vasudevan and Vaidyanathan, 2017).

2.4.1 Mechanism of action of Vitamin K in Animals

Vitamin K is the prosthetic group for the carboxylation of glutamate residues in the post-synthetic

modification of proteins to form the unusual amino acid γ-carboxyglutamate (Glu), which

chelates the calcium ion. Vitamin K hydroquinone is oxidized to the epoxide which activates a

glutamate residue in the protein substrate to a carbanion that reacts non-enzymically with carbon
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dioxide to form γ-carboxyglutamate. Vitamin K epoxide is reduced to the quinone by a warfarin-

sensitive reductase, and the quinone is reduced to the active hydroquinone by either the same

warfarin-sensitive reductase or a warfarin-insensitive quinone reductase (Bender and Mayes,

2003). In the presence of warfarin, vitamin K epoxide cannot be reduced but accumulates, and is

excreted. If enough vitamin K (a quinone) is provided in the diet, it can be reduced to the active

hydroquinone by the warfarin-insensitive enzyme and carboxylation can continue with the

utilization of vitamin K and excretion of the epoxide. A high dose of vitamin K is the antidote to

an overdose of warfarin. Prothrombin and several other proteins of the blood clotting system each

contain between four and six γ-carboxyglutamate residues which chelate calcium ions and so

permit the binding of the blood clotting proteins to membranes (Bender and Mayes, 2003).

In vitamin K deficiency or in the presence of warfarin, an abnormal precursor of prothrombin

(preprothrombin) containing little or no γ-carboxyglutamate, and incapable of chelating calcium,

is released into the circulation. Treatment of pregnant women with warfarin can lead to fetal bone

abnormalities (fetal warfarin syndrome). Two proteins are present in bone that contain γ-

carboxyglutamate, osteocalcin and bone matrix Glu protein. Osteocalcin also contains

hydroxyproline, so its synthesis is dependent on both vitamins K, C and D (Uotila, 1990).

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 SECTION THREE

3.0 SUMMARY

Vitamins are a group of organic nutrients required in small quantities for a variety of biochemical

functions such as metabolism, maintenance of health and proper growth which cannot be

generally synthesized by the body and must be supplied in the diet. Vitamins are classified as

water-soluble and fat soluble. Fat-soluble vitamins include vitamin A, Vitamin D, Vitamin E and

Vitamin K. Vitamin A primarily known as retinol is a pale-yellow, primary alcohol derived from

carotene, having an aldehyde form, retinal and acidic form, retinoic acid. Vitamin A is essential

for vision and eye health. Vitamin A also functions in the control of cell differentiation and turn

over by the binding action of nuclear receptors to response elements of DNA regulating the

transcription of specific genes. Vitamin D (Calcitriol) is a steroid hormone that is involved in

regulating body levels of calcium, phosphorus and in mineralization of bones. Vitamin D occurs

in two forms, Vitamin D2 and D3. Vitamin D is obtained from adequate sunlight and must be

metabolized into its hormonally active form, 1,25-dihydroxycholecalciferol to carry out

biological functions such as binding to intracellular receptors that functions as transcription

factors to modulate gene expression and maintain plasma calcium concentration. Vitamin E

(Tocopherol) is a fat-soluble vitamin with several forms but having alpha-tocopherol as the only

form used by the human body. Vitamin E serve as antioxidants in cell membranes. Vitamin K

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 (Phylloquinone) functions as a prosthetic group for the carboxylation of glutamate residues in the

post-synthetic modification of proteins to form amino acid, gamma-carboxyglutamate which

chelates the calcium ion. The Fat-soluble vitamins A, D, E and K are important for a wide variety

of physiological functions.

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