Biochemistry and Molecular Biology Resource

 

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Eric C. Niederhoffer, Ph.D.

Associate Professor of Biochemistry and Molecular Biology

Southern Illinois University School of Medicine
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eniederhoffer@siumed.edu
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Vitamins


Vitamins are low molecular weight organic molecules that are needed to promote a variety of biological processes important to life. They are generally not made in sufficient quantities in our cells and therefore must be obtained through the diet. Information concerning dietary intake requirements and food sources may be obtained from the Food and Nutrition Information Center (United States Department of Agriculture).

Classification and Nomenclature

The first representatives were initially discovered through separation of water- and fat-soluble components of butter fat This led to classifiying vitamins as water-soluble and fat-soluble.

Vitamin Classification

Water soluble

 

Fat soluble

A, D, E, K

B-complex

 

non B-complex

C

Energy releasing

B1, B2, B3, B5, B7

Hematopoietic

B9, B12

Other

B6, choline, inositol, carnitine, p-aminobenzoic acid, coenzyme Q, lipoic acid, bioflavinoids

 

The original nomenclature was alphabetical in order of discovery (based on correcting some disease or problem) with subscripts added for related molecules. As the structure of each vitamins was determined, chemical names were provided.

Vitamin Nomenclature

Common Historical

  Common Chemical

A
retinol, retinal, retinoic acid
B1 (antiberiberi factor)
thiamin(e)
B2
riboflavin
B3 (antipellagra factor)
niacin, nicotinic acid, nicotinamide
B5
pantothenic acid
B6
pyridoxine, pyridoxal, pyridoxamine
B7
biotin
B9
folacin, folic acid
B12 (antipernicious anemia factor
cobalamin
C (antiscorbic factor)
ascorbic acid
D (antirachitic factor)
cholecalciferol (D3), ergocalciferol (D2)]
E
tocopherol
K (antihemmorrhagic factor)
phylloquinone, phytylmetnaquinone, phytomenadione (all K1), menaquinone-4 to menaquinone-13 (all K2)

Fat Soluble Vitamins

Vitamin A

Vitamin A is most commonly associated with rhodopsin (cis-retinal plus the photoreceptor protein opsin) of the visual system. The provitamin is obtained through the diet from plants rich in carotenoids (α-, β-, and γ-carotenes), which is then processed in the body, and from animals that have processed the precursor into the active form. Retinoic acid acts as a ligand for specific nuclear receptors (retinoic acid receptors and retinoid X receptors) that regulate gene transcription. Excessive amounts of the vitamin are toxic (150 mg single dose or 5000 IU/day for several years).

Vitamin A Forms

 

β-carotene (provitamin A)

retinol

retinal (retinaldehyde)

retinoic acid

Vitamin D

Vitamin D is also know as the "sunshine" vitamin because sun light converts the precursor 7-dehydrocholesterol, which is found in the skin of animals and humans, into vitamin D3. Ricketts was found to be cured by this fat-soluble factor. Ergocalciferol (D2) is obtained from the irradiation of the plant steroid ergosterol. Both vitamin D3 and D2 are converted in the body through a series of hydroxylations, first to 25-hydroxycholecalciferol (25-ergocalciferol) in the liver, and then 1,25-dihydroxycholecalciferol (1,25-dihydroxyergocalciferol) in the kidneys, the active form (also denoted as calcitriol). The active calcitriol functions are a hormone, binding to vitamin D receptors (nuclear receptors).

Vitamin D Forms

cholecalciferol (D3)

 

ergocalciferol (D2)

1,25-dihydroxycholecalciferol (calcitriol)

active hormone binds to Vit D receptors

 

Vitamin E

Vitamin E was found during studies on the impact of plant oils on reproduction and provided the name tocopherol (tokos = child birth; pherein = to bear; with "ol" at the end to signify an alcohol). The most active forms of the vitamin have been isolated from plant oils and are indicated in the table below. As a fat-soluble molecule that is easily oxidized, it is found associated with cell membranes where it serves as a lipid antioxidant.

Vitamin E (active) Forms

α-tocopherol

α-tocotrienol

β-tocopherol

γ-tocopherol

 

Vitamin K

Vitamin K (K for koagulation) was found to promote blood clotting (coagulation). Three forms exist. K1 was isolated from alfalfa (green plants) and is called phylloquinone, phytylmenaquinone, or phytomenadione. K2 was isolated from putrefied fish meal and group of related molecules are called menaquinone-4 to menaquinone-13, indicating the number of isoprenyl units associated with the molecule. K3 is a synthetic form containing no isoprenyl groups (menadione); it is no longer used because of its toxicity. The vitamin is involved in carboxylase mediated reactions that convert glutamic acid residues to γ-carboxyglutamic acid (posttranslational modifications), a residue with side groups that bind Ca2+. The well known coagulation proteins prothrombin, factors VII, IX, and X are required for blood clotting.

Vitamin K Forms

phylloquinone (K1)

menaquinone (K2)

 

menadione (K3)

 

Water Soluble Vitamins

Vitamin B1

Beriberi is a paralyzing disease (Singhalese, beri = weakness) that was cured by providing less polished rice (vitamin is associated with the germ). Thiamin (or thiamine) is converted into the active form (thiamin pyrophosphate, TPP) by the action of thiamin pyrophosphate kinase:

Thiamin is required for pyruvate dehydrogenase (link between glycolysis and citric acid cycle), α-ketoglutarate dehydrogenase (citric acid cycle), α-ketoacid dehydrogenases (branched-chain amino acid oxidation), and transketolase (pentose phosphate pathway). Thiamin is rapidly excreted in the urine along with its metabolic products (major products are pyridine acetic acid and thiazole acetic acid). Thiamin levels can be obtained by colorimetric assay of the urine or, in a more accurate assessment, functional measurement of metabolic reations. The most useful for the latter approach is determining transketolase activity in red blood cells.

Vitamin B1 Forms

thiamin (thiamine)

thiamin pyrophosphate (TPP)

 

Vitamin B2

Vitamin B2 (riboflavin) was initially discovered as the heat-stable yellow-green fluorescent component of water-soluble vitamin B. Riboflavin is processed in the body to form the two prosthetic groups flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Note that the sugar derivative connected to the flavin is a reduced sugar (polyhydric alcohol) rather than the ribose of a typical nucleotide. Interconversions between riboflavin, FMN, and FAD are illustrated below.

By definition, prosthetic groups FMN and FAD are tightly or covalently bound to their respective proteins. These flavoproteins include acyl CoA dehydrognease (β-oxidation), amino acid oxidases, cytochrome c reductase, glutathione reductase (oxidative stress defense), α-ketoacid dehydrogenases, α-ketoglutarate dehydrogenase, pyruvate dehydrogenase, succinate dehydrogenase (complex I of the respiratory chain), xanthine oxidase (purine catabolism).

Vitamin B2 Forms

riboflavin
flavin mononucleotide (FMN)

flavin adenine dinucleotide, oxidized

FAD

flavin adenine dinucleotide, reduced

FADH2

 

Vitamin B3

Vitamin B3 (niacin, nicotinic acid) is not strictly a vitamin because it can be produced from the metabolism of tryptophan. It is associated with the disease pellegra (pelle=skin, agra=rough), which in chronic cases is characterized by dermatitis, diarrhea, and dementia. High doses of niacin are useful as an antihyperlipidemic. The redox pair NAD+/NADH associations include glyceraldehyde-3-phosphate dehydrogenase (glycolysis), lactate dehydrogenase (anaerobic glycolysis), pyruvate dehydrogenase, isocitrate dehydrogenae, α-ketoglutarate dehydrogenase, glucose-6-phosphate dehydrogenase (NADPH, pentose phosphate pathway), 6-phosphogluconate dehydrogenase (NADPH, pentose phosphate pathway), complex I of the respiratory chain, and enzymes of both amino acid and fatty acid oxidation.

Vitamin B3 Forms

niacin (nicotinic acid)

nicotinamide

nicotinamide adenine dinucleotide, oxidized

NAD+

nicotinamide adenine dinucleotide, reduced

NADH

nicotinamide adenine dinucleotide phosphate, oxidized

NADP+

nicotinamide adenine dinucleotide phosphate, reduced

NADPH

 

Vitamin B5

Vitamin B5 (pantothenic acid, pantos = everywhere) consists of pantoic acid and β-alanine. It is processed in the body to become a component of coenzyme A (amino acid, carbohydrate, and lipid metabolism) and acyl carrier protein (fatty acid synthesis).

Vitamin B5 Forms

pantothenic acid

coenzyme A

CoASH

 

Vitamin B6

Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine) along with their 5'-phosphates) are involved in amino acid metabolism (alanine aminotransferase, aspartate aminotransferase, branched-chain amino acid aminotransferases, cystathionine synthase, kynurenininase, and aromatic amino acid decarboxylase), glycogen degradation (glycogen phosphorylase), porphyrin synthesis (δ-aminolevulinic acid synthetase), and in removing steroid hormone-receptor complex from DNA. There are kinases and phosphatases involved in adding or removing the phosphate group (OPO3-) and pyridoxine phosphate oxidase and aminotransferase for interconverting pyridoxine-, pyridoxal-, and pyridoxamine-5'-phosphate.

Vitamin B6 Forms

pyridoxine

pyridoxal

pyridoxamine

pyridoxine-5-phosphate

pyridoxal-5-phosphate

pyridoxamine-5-phosphate

 

Vitamin B7

Vitamin B7 (biotin, bios = life) is a prosthetic group of four enzymes in the body, pyruvate carboxylase, acetyl CoA carboxylase, propionyl CoA carboxylase, and β-methyl crotonyl CoA carboxylase. It is linked by an amide bond to a lysine (Lys) residue on the corresponding carboxylase enzyme.

Vitamin B7 Forms

biotin

binds to avidin found in raw egg whites

biocytin

carboxybiocytin

active intermediate

 

Vitamin B9

Vitamin B9 (folic acid or folacin, folium = leaf) is comprised of pteridine, p-aminobenzoic acid, and glutamic acid. Once absorbed into cells, folic acid is reduced to dihydrofolate and then to tetrahydrofolate; both steps catalyzed by dihydrofolate reductase. The major form is the reduced N5-methyl-tetrahydrofolate (N5-methyl-THF (look for the four H in the figure below). There are various intermediates of THF that serve as acceptors and donors of 1-carbon units. These include purine and thymidine synthesis (thymidylate synthase), interconversion of histidine-glutamate (glutamate formiminotransferase), serine-glycine (serine hydroxymethyl transferase), homocysteine-methionine (methionine synthase). Thus folic acid is important for RNA and DNA synthesis, which impacts cell growth and division. A deficiency in folic acid can lead to megaloblastic anemia.

Vitamin B9 Forms

folic acid (folacin)

N5-methyl-tetrahydrofolate (N5-methyl-THF)

 

Vitamin B12

Vitamin B12 (cobalamin, deoxyadenosylcobalamin, methylcobalamin) contains a cobalt ion as part of the porphyrin-like corrin ring. Uptake of extrinsic vitamin B12 requires the presence of intrinsic factor. There are two reactions of importance that require cobalamin. Recycling of methionine (homocysteine to methionine) utilizes methionine synthase, which is also dependent on folic acid, and the conversion of L-methylmalonyl CoA into succinyl CoA (methylmalonyl CoA mutase). A deficiency of vitamin B12 can lead to both megaloblastic (pernicious, if intrinsic factor is deficient)) anemia and neuropathy. Because folic acid defuciency also can lead to megaloblastic anemia, treating for folic acid deficiency alone can mask cobalamin deficiency if neuropathy is not considered.

Vitamin B12 Forms

deoxyadenosylcobalamin (R = 5-deoxyadenosyl)

methylcobalamin (R = methyl)

 

Vitamin C

Vitamin C (ascorbic acid) is important in the evolution of travel. Long trips were enabled by including citrus juices. This antiscorbutic factor (scorbutic = scurvy) has important roles in oxidation-reduction reactions (copper-containing hydroxylases). Enzymes include proline and lysine hydroxylase (collagen crosslinking) and dopamine β-hydroxylase (adrenaline formation from tyrosine). Vitamin C also plays a role in oxidative stress (free radical scavenger).

Vitamin C Forms

ascorbic acid

dehydroascorbic acid

 

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