Vitamins: Types, Function & Classification

Vitamins Overview

• Organic compounds essential for biochemical reactions that act as coenzymes
• Not part of tissues, required in very small amounts
• Provitamins are precursors that convert into active vitamins
• Vitamers are different forms of the same vitamin
• Vitamin D has two vitamers: D2 and D3

Classification Of Vitamins

• Fat-soluble vitamins include A, D, E, and K
  • Dissolve in fat, require bile salts for absorption, and can be stored
• Water-soluble vitamins include vitamin C and B-complex
  • Dissolve in water and are mostly not stored, intake should be regular

Vitamin A (Retinoids)

Structure and Forms

• Provitamin A: Carotenoids, such as beta-carotene
• Active Forms: Retinol, Retinal, and Retinoic Acid

Sources

• Animal sources include liver, eggs, milk fat, and fish liver oils
• Plant sources include carrots, potatoes, and tomatoes (contain carotenoids)

Absorption and Storage

• Dietary retinol esters break down into fatty acids and retinol
• Beta-carotene converts into retinal by an enzyme after absorption
• Retinal then converts into retinol
• Retinol re-esterifies within intestinal cells with fatty acids
• Transport into the lymphatic system, reaches general circulation, and is primarily stored in the liver (90%)

Functions

• Functions like a hormone by interacting with genes and nuclear proteins
• Retinal is essential for night vision
• Retinol aids sperm production in males and supports fetal development in females
• Needed for bone and teeth creation and normal growth
• Maintains smooth skin, mucous membranes, and a healthy cornea
• Helps in glycoprotein synthesis, lung surfactant production, and cell differentiation
• Retinoids and carotenoids act as antioxidants, protecting tissues from damage and lowers epithelial cancers

Deficiency

• Night blindness is difficulty seeing in the dark
• Xerophthalmia: dry, rough cornea
• Stunted growth in children
• Rough, dry skin ("goose skin")
• Weakened mucous membranes can lead to infections

Daily requirement

• The daily Vitamin A requirement is 5000 IU

Vitamin A Toxicity

• Occurs when intake exceeds storage capacity
  • Headache and nausea
  • Bone pain
  • Hair loss

Vitamin K

• K1 is found in plants, K2 is produced by intestinal bacteria, K3 is synthetically made, water-soluble, and more potent

Sources

• Intestinal bacteria (K2), plants (K1), and synthetic production (K3)

Functions

• Essential for the synthesis of blood clotting factors (II, VII, IX, X) in the liver
• Important for the production of osteocalcin, a calcium-binding protein in bones

Mechanism of Action

• Vitamin K activates prothrombin by carboxylation of glutamic acid residues, turning it into thrombin

Deficiency

• Newborns (due to a sterile intestine)
• Long-term use of antibiotics (which kill gut bacteria)
• Liver diseases (affects prothrombin synthesis and bile salts which help Vit K abosrption)
• Use of anticoagulants (e.g., warfarin, inhibits vitamin K function)

Role in bone health

• Converts pro-osteocalcin into active osteocalcin, helping in bone mineralization

Vitamin E

Forms

• Four forms (α, β, γ, δ) are Vitamin E, with alpha-tocopherol being the most active

Sources

• Vegetable oils, leafy greens, and fish liver oils

Functions

• Powerful antioxidant that protects cells from oxidative damage caused by free radicals
• Prevents oxidation of polyunsaturated fatty acids (PUFAs) in cell membranes
• Prevents atherosclerosis & heart disease by stopping LDL oxidation

Deficiency

• More common in premature infants
• Leads to RBC hemolysis (anemia) and muscle weakness

Daily requirement

• The daily Vitamin E requirement is 15 IU
• Plays an essential role in blood clotting and bone health
• Acts as a powerful antioxidant that supports cells and heart health

Vitamin D

Sources

• Sunlight (UV rays) converts provitamins (ergosterol in plants & 7-dehydrocholesterol in humans) into active vitamin D
• Food sources: Liver, eggs, yeast, and fish liver oils

Activation

• Vitamin D3 (Cholecalciferol) is synthesized in the skin through sunlight exposure
• The liver converts it into 25-hydroxycholecalciferol
• The kidney activates it to 1,25-dihydroxycholecalciferol (Calcitriol), the active hormone form

Functions

• Regulates Serum Calcium Levels
  • Intestine: Increases calcium absorption by stimulating calbindin protein
  • Bones: Helps in calcium reabsorption
  • Kidneys: Enhances calcium reabsorption from urine
• Bone Mineralization
  • Small doses: Support bone strength by increasing calcium and phosphate levels
  • Large doses: Cause calcium and phosphate to move from bones to blood
• Phosphate Absorption
  • Enhances intestinal and renal absorption of phosphate
• Osteocalcin Synthesis
  • Promotes bone health by stimulating pro-osteocalcin production

Deficiency

• Rickets is soft, deformed bones in children
• Osteomalacia is weak, brittle bones leading to fractures in adults
• Renal Rickets: Seen in chronic kidney disease due to impaired activation of vitamin D

Daily requirement

• The daily RDA is 400 IU of Vitamin D

Vitamin D Overdose

• Leads to abnormal calcium deposition, causing kidney stones and tissue calcification
• Vitamin D is crucial for calcium & phosphate balance, bone health, and hormonal regulation Deficiency causes rickets & osteomalacia, while excess leads to kidney stones & tissue calcification

Vitamin C (L-Ascorbic Acid)

Sources

• Citrus fruits (lemon, orange), melon, strawberry, and guava (richest source)
• Green leafy vegetables (lettuce), tomatoes, potatoes, raw cabbage, and green peppers

Chemical Properties

• Highly sensitive to heat, light, and oxidation
• Exists in two active forms: L-ascorbic acid (90%) and Dehydro-L-ascorbic acid (10%)
• Further oxidation converts it into oxalic acid

Functions

• Collagen Formation
  • Essential for converting procollagen into collagen
  • Involves hydroxylation of proline & lysine via vitamin C as a coenzyme
• Iron Absorption & Mobilization
  • Keeps iron in its ferrous (Fe2+) form
• Coenzyme in Syntheses
  • Bile acid synthesis, osteocalcin synthesis, carnitine synthesis, and epinephrine synthesis
• Antioxidant Action
  • Protects tissues oxidative damage and reduces the risk of cancer

Deficiency

• Vitamin C stores last 3 months, deficiency leads to Scurvy

Collagen Deficiency Symptoms

• Bleeding (gums, muscles, joints, kidneys, GI tract, pericardium)
• Weak bones & teeth formation and slow wound healing
• Anemia results from iron absorption & bleeding
• Neurotransmitter Deficiency causes emotional & behavioral changes
• Energy Deficiency is weakness due to carnitine & fatty acid oxidation

Overdose

• Hyperoxaluria (high oxalate in urine) increasing the risk of kidney stone formation
• Vitamin C is vital for collagen synthesis, iron absorption, antioxidant protection, and neurotransmitter production
  • Deficiency causes scurvy (bleeding, weak bones, anemia)
  • Excess can lead to kidney stones

Vitamin B Complex

• All B vitamins are water-soluble and found in the same food sources, such as whole grains, liver, and yeast
• Act as coenzymes in chemical reactions, especially in the formation of red blood cells (folic acid and vitamin B12)
• Absorbed in the intestines and enter the bloodstream, the body stores small amounts of them, and these stores deplete quickly if there are dietary restrictions or increased needs

Vitamin B1 (Thiamine)

Sources

• Found in whole grains, legumes, yeast, unpolished rice, and whole wheat bread

Functions

• Helps in carbohydrate metabolism by acting as a coenzyme for keto acid reactions (pyruvate) and essential for energy production and nerve function, it also helps in sodium transport across nerve membranes

Deficiency

• Dry Beriberi: Causes nerve damage and muscle weakness
• Wet Beriberi: Leads to heart failure and swelling (edema)

Daily requirement

• The daily RDA is 1.5mg of Vitamin B1

Vitamin B2 (Riboflavin)

Sources

• Milk and dairy products, eggs, liver, and green leafy vegetables

Structure

• Composed of a flavin ring attached to ribitol (a sugar alcohol)

Active Forms

• FMN (Flavin Mononucleotide): Formed when riboflavin is phosphorylated by ATP with the help of intestinal flavokinase
• FAD (Flavin Adenine Dinucleotide): Formed by adding AMP from ATP to FMN

Functions

• Important in energy production
• Example reactions contain succinate + FAD → Succinate dehydrogenase → Fumarate + FADH2

Deficiency

• Deficiency is not fatal, but leads to
  • Ocular disturbances: Photophobia (light sensitivity) and vascularization of the cornea
  • Cheilosis: Fissuring at the corners of the mouth
  • Glossitis: Inflammation of the tongue, which appears smooth and purplish
  • Dermatitis: Inflammation of the skin

Daily requirement

• The daily RDA is 1.5mg of Vitamin B2

Vitamin B3 (Niacin or Nicotinic Acid)

Sources

• Whole grain cereals, milk, meat, liver, and yeast
• Synthesis: the amino acid tryptophan converts to niacin (1 mg of niacin produced for every 60 mg of tryptophan). Requires vitamin B6

Structure

• Is a pyridine derivative, non-toxic, a toxic alkaloid version (nicotine) is found in tobacco

Active Forms

• Niacin converts to nicotinamide, which forms NAD (Nicotinamide Adenine Dinucleotide) and NADP (Nicotinamide Adenine Dinucleotide Phosphate); essential for biochemical reactions

Functions

• Formation of NAD and NADP: the coenzymes are vital for carbohydrate, protein, and lipid metabolism
• Cholesterol Lowering: it can reduce plasma cholesterol by inhibiting the release of free fatty acids from fat tissue
• Formation of ADP-ribose: involved in the ADP-ribosylation of proteins and in DNA repair mechanisms

Deficiency

• Niacin deficiency leads to pellagra, characterized by the 3 D's: diarrhea, dermatitis, dementia, and death (if untreated)

Daily requirement

• The daily Vitamin B3 RDA is 20mg

Toxicity

• High doses (more than 500 mg/day) can cause liver damage.

Pyridoxine (Vitamin B6)

Sources and Structure

• Wheat, corn, egg yolk, liver, and meat
• Is a group of vitamers derived from the pyridine ring; these vitamers are pyridoxine, pyridoxal, and pyridoxamine
• All three act as precursors to the biologically active coenzyme pyridoxal phosphate

Functions

• Is essential in amino acid metabolism
• Synthesis of heme from glycine and succinyl CoA, Niacin (vitamin B3) from tryptophan, and sphingosine from serine and palmitate
• Is involved in glycogen breakdown (glycogenolysis)
• Involved in steroid hormone action via releasing hormone-receptor complexes from DNA

Deficiency

• Pellagra from impaired tryptophan to niacin conversion
• Convulsions in infants may be due to insufficient GABA
• Anemia (microcytic and hypochromic) can result
• Disturbance in amino acid metabolism may lead to growth and mental retardation
• Cancer can result from defective DNA-steroid binding of the breast, uterus, and prostate
• Elevated homocysteine from impaired conversion of methionine to cysteine

Toxicity

• Excessive intake (more than 200 mg/day) potentially causes neurological damage

Pantothenic Acid (Vitamin B5)

Sources

• Pantothenic Acid is found in animal tissues such as meat, liver, and kidney, and in legumes

Structure

• Pantothenic acid consists of pantothenic acid (a and y dihydroxy dimethyl butyric acid) connected to β-alanine

Functions

• No significant effect if removed from the body in humans

Daily requirement is 5-10 mg

Biotin (Vitamin B7)

Sources

• Intestinal bacteria synthesize most of the required biotin, but found additional sources like egg yolk, animal tissues, tomatoes, and yeast

Absorption

• Occurs in the ileum

Structure

• Consists of a thiophene ring attached to urea with a valeric acid side chain, it functions as a C02 carrier for carboxylase enzymes

Functions

• C02 fixation in reactions like acetyl CoA → malonyl CoA (fatty acid synthesis) and pyruvate → oxaloacetate (gluconeogenesis), it also helps in regulation of the cell cycle

Deficiency

• Biotin deficiency is rare but may occur with excessive ingestion of avidin or in cases of enzyme deficiency (holocarboxylase synthetase)

Vitamin B12 (Cobalamin)

Sources

• It can be found in meat, egg, milk, and milk products.
• Intestinal microorganisms also synthesize B12, but it is not absorbed in the colon.

Structure

• Consists of a corin ring with a cobalt ion at the center, and a nucleotide side chain.
• Can be in various forms, such as cyanocobalamin, methylcobalamin, and adenosylcobalamin.

Absorption

• B12 binds to cobalophilin in the mouth, and in the duodenum, it binds to intrinsic factor (IF). The IF-B12 complex is absorbed in the ileum and transported by transcobalamin to tissues.

Functions

• Needed for synthesizing methionine from homocysteine
• Involved in cell division and hematopoiesis
• Myelin formation

Deficiency

• May cause megaloblastic anemia due to impaired DNA replication in hematopoietic tissue, it causes Neurological Manifestations due to a deficient myelin sheath formation
• Pernicious Anemia may result from destruction of gastric parietal cells, leading to a lack of intrinsic factor

Sources of Folic Acid

• Leafy vegetables are a major source, other sources include liver, beans, and whole grain cereals

Structure

• Consists of pteroic acid conjugated to one or more glutamic acid residues
• Pterolic acid consists of a pteridine ring and para-aminobenzoic acid (PAВА)
• In plants, folic acid contains glutamic acid residues, typically two to seven, attached to the carbon of glutamate

Absorption

• Pteroylpolyglutamate is broken down into pteroylmonoglutamate by intestinal folypolyglutamate hydrolase in the jejunum
• Pteroylmonoglutamate is its form absorbed by the intestine
• Folate transport happens into the liver through the portal circulation
• In the liver, folate converts into dihydrofolate (H2 folate) and tetrahydrofolate (H4 folate)
• Then, some tetrahydrofolate becomes polyglutamate, which is stored in the liver
• Fraction of folate is excreted through bile as N5-methyl tetrahydrofolate

Functions

• Its active form, tetrahydrofolic acid (H4 folate), works as a carrier of one-carbon groups for different biochemical reactions, and synthesis happens for DNA and RNA through purine synthesis (adenine and guanine) and methylation of uracil to thymine, also creating nonessential amino acids like serine and glycine and converting homocysteine to methionine

Sources of One-Carbon Groups

• Sources of one-carbon groups, like the serine carbon is a major contribution
• Also contains tryptophan and histidine

Fate and Functions of One-Carbon Groups

• One-carbon groups assist to help in the creation of glycine and serine, uracil to thymine, convert homocysteine to methionine, and construct purines (adenine and guanine)

Deficiency

• Can cause defective DNA and RNA synthesis, affecting cell formation, including blood cells
• Causes manifestations of deficiency like Pancytopenia affecting all blood cells, Megaloblastic anemia, Leucopenia, Thrombocytopenia
• Also causes impaired growth and neural tube defects in the fetus

Drugs Inhibiting Folic Acid Formulation

• Trimethoprim which inhibits bacterial folate reductase and affects bacteria only
• Methotrexate which is used in chemotherapy inhibits both human and microorganisms strongly