Vitamins

BiochemistryUpdated 6 min read
On this page 18 sections
Figure: Vitamins

Fat Soluble

Vitamin & Chemical NameKey Functions & MCQ NotesMain SourcesDeficiency Manifestations
Vitamin A

(Retinol, Retinal, Retinoic acid)
• Vision (constituent of rhodopsin)

• Epithelial tissue maintenance & immunity

• Teratogenic in excess
Liver, fish liver oils, carrots, dark leafy greens (beta-carotene)• Night blindness (Nyctalopia - earliest sign)

• Xerophthalmia & Bitot's spots

• Keratomalacia

• Follicular hyperkeratosis
Vitamin D

(D₂: Ergocalciferol, D₃: Cholecalciferol)
• Calcium & phosphate absorption

• Active form: 1,25\-(OH)_2\D_3 (Calcitriol)

• Activated by hydroxylation in liver (25) & kidney (1)
Sunlight exposure, fatty fish, egg yolk, fortified milk

Cod Liver oil
• Rickets in children (bow legs, rachitic rosary)

• Osteomalacia in adults (soft bones)

• Hypocalcemia
Vitamin E

(Tocopherol)
• Major lipid-soluble antioxidant

• Protects cell membranes & RBCs from peroxidation
Vegetable oils, nuts, seeds, wheat germ• Hemolytic anemia (especially in premature infants)

• Neurological deficits (spinocerebellar ataxia, muscle weakness)
Vitamin K

(K₁: Phylloquinone, K₂: Menaquinone)
• Essential for γ-carboxylation of Clotting Factors II, VII, IX, X and Proteins C & S

• Inhibited by Warfarin
Green leafy vegetables; synthesized by gut flora• Prolonged Prothrombin Time (PT) & Bleeding Time

• Hemorrhagic disease of the newborn (sterile gut at birth)

Vitamin A

Vitamin A supports retinal function and normal epithelial differentiation.

  • Retinal is required for visual phototransduction.
  • Retinoic acid regulates gene transcription and epithelial differentiation.
  • Deficiency can cause night blindness, conjunctival xerosis and Bitot spots.
  • Severe deficiency can cause corneal damage and keratomalacia.

Clinical correlation: Vitamin A deficiency may affect oral and respiratory epithelium as well as vision.

Vitamin D

Vitamin D promotes intestinal calcium and phosphate absorption and supports normal bone mineralization.

DeficiencyTypical manifestation
ChildrenRickets
AdultsOsteomalacia
Severe deficiencyBone pain, muscle weakness and increased fracture risk

Vitamin D is activated through hydroxylation in the liver and kidneys. The kidney produces 1,25-dihydroxyvitamin D (calcitriol), the active hormonal form.

Vitamin E

Vitamin E protects cell membranes from oxidative damage.

Deficiency may cause:

  • Hemolytic anemia.
  • Peripheral neuropathy.
  • Ataxia and impaired proprioception, particularly in severe deficiency or malabsorption.

Vitamin K

Vitamin K is required for gamma-carboxylation of glutamate residues in coagulation proteins.

Important vitamin K-dependent proteins include:

  • Factors II, VII, IX and X.
  • Proteins C and S.

Deficiency impairs normal clotting and can prolong PT/INR, often early because factor VII has a relatively short half-life.

Remember: Vitamin K deficiency affects clotting factor function, not simply their production.

Water soluble

Vitamin & Chemical NameKey Functions & MCQ NotesMain SourcesDeficiency Manifestations
Vitamin B₁

(Thiamine)
• Coenzyme: TPP (Thiamine pyrophosphate)

• Key enzymes: Pyruvate dehydrogenase, Transketolase
Whole grains, legumes, pork, unpolished rice• Beriberi:

- Dry: Peripheral neuropathy

- Wet: High-output heart failure / edema

• Wernicke-Korsakoff syndrome (triad: ataxia, confusion, ophthalmoplegia; seen in chronic alcoholism)
Vitamin B₂

(Riboflavin)
• Coenzymes: FAD, FMN (redox reactions)

• Derived from ribitol + flavin
Milk, eggs, liver, green vegetables• Cheilosis (cracks at corners of mouth)

• Angular stomatitis & Glossitis (magenta tongue)

• Corneal neovascularization
Vitamin B₃

(Niacin / Nicotinic Acid)
• Coenzymes: NAD⁺, NADP⁺

• Synthesized from Tryptophan (requires $B_6$)

• Excess causes cutaneous flushing
Meat, fish, poultry, grains, legumes• Pellagra (3 Ds):

- Dermatitis (Casal's necklace pattern)

- Diarrhea

- Dementia

(Can lead to Death if untreated)
Vitamin B₅

(Pantothenic Acid)
• Component of Coenzyme A (CoA) & Fatty Acid SynthaseWidely distributed in foods ("pan" = everywhere)• "Burning feet" syndrome (paresthesias)

• Adrenal insufficiency, alopecia
Vitamin B₆

(Pyridoxine)
• Active form: PLP (Pyridoxal phosphate)

• Required for transamination, decarboxylation, & heme synthesis

• Elevated requirement with high protein intake & Isoniazid (INH) therapy
Meat, bananas, whole grains, nuts• Peripheral neuropathy (prevented by giving B_6 with INH)

• Microcytic sideroblastic anemia

• Convulsions / Seizures
Vitamin B₇

(Biotin)
• Coenzyme for Carboxylation reactions (e.g., Pyruvate carboxylase)

• Antagonized by Avidin in raw egg whites
Egg yolk, liver, produced by intestinal bacteria• Dermatitis, alopecia, muscle pain, paresthesias
Vitamin B₉

(Folic Acid / Folate)
• Active form: THF (Tetrahydrofolate)

• One-carbon transfers (DNA synthesis)

• No neurological signs (unlike B_12
Green leafy vegetables ("folium"), legumes, liver• Megaloblastic anemia (hypersegmented neutrophils)

• Neural tube defects (spina bifida in fetus)
Vitamin B₁₂

(Cobalamin)
• Contains Cobalt; required for DNA synthesis & myelin maintenance

• Requires Intrinsic Factor (IF) from parietal cells for absorption in terminal ileum
Meat, fish, eggs, dairy (absent in plants / strict vegans)• Pernicious anemia (Megaloblastic anemia + IF deficiency)

• Subacute combined degeneration (SCD) of spinal cord (neurological damage)
Vitamin C

(Ascorbic Acid)
• Hydroxylation of Proline & Lysine in collagen synthesis

• Antioxidant; enhances non-heme iron absorption
Citrus fruits, tomatoes, berries, broccoli, peppers• Scurvy:

- Bleeding / swollen gums, loose teeth

- Poor wound healing

- Perifollicular hemorrhages & petechiae

Vitamin B1 — Thiamine

Thiamine is converted into thiamine pyrophosphate (TPP), a cofactor for several important enzymes.

Major TPP-dependent enzymes:

  • Pyruvate dehydrogenase.
  • α-Ketoglutarate dehydrogenase.
  • Branched-chain α-ketoacid dehydrogenase.
  • Transketolase.
Deficiency syndromeKey findings
Dry beriberiPeripheral neuropathy and muscle wasting
Wet beriberiCardiovascular dysfunction and edema
Wernicke encephalopathyConfusion, ataxia and ophthalmoplegia
Korsakoff syndromeMemory impairment and confabulation

Exam tip: Give thiamine before or alongside glucose in patients at risk of deficiency, particularly those with severe malnutrition or chronic alcohol use.

Vitamin B2 — Riboflavin

Riboflavin forms FAD and FMN, which participate in oxidation-reduction reactions.

Deficiency may cause angular cheilitis, glossitis and inflammation of oral mucosa.

Vitamin B3 — Niacin

Niacin is required for synthesis of NAD and NADP.

Pellagra is classically associated with the 3 Ds:

  • Dermatitis.
  • Diarrhea.
  • Dementia.

Severe untreated deficiency can be fatal.

Vitamin B6 — Pyridoxine

Vitamin B6, in its active form pyridoxal phosphate (PLP), acts as a cofactor in amino acid metabolism, neurotransmitter synthesis and heme production.

Deficiency may cause neuropathy, seizures and sideroblastic anemia.

Drug association: Isoniazid can cause B6 deficiency; pyridoxine supplementation is used in appropriate patients to prevent or treat it.

Vitamin B9 versus B12

FeatureFolate (B9)Cobalamin (B12)
Main roleDNA synthesis and one-carbon transferDNA synthesis and neurologic function
Deficiency anemiaMegaloblasticMegaloblastic
Neurologic dysfunctionNot characteristicMay be prominent
HomocysteineIncreasedIncreased
Methylmalonic acidUsually normalIncreased
Major dietary sourcesLeafy vegetables, legumes and fortified grainsAnimal-derived foods and fortified foods

Critical exam point: Folate can correct the anemia of B12 deficiency without preventing progressive neurologic injury. Assess for B12 deficiency before treating unexplained megaloblastic anemia with folate alone.

Vitamin C — Ascorbic acid

Vitamin C is needed for hydroxylation of proline and lysine during collagen synthesis.

Deficiency causes scurvy, characterized by:

  • Bleeding gums.
  • Petechiae and perifollicular hemorrhage.
  • Poor wound healing.
  • Easy bruising.
  • Impaired collagen formation.

Clinical correlations

Clinical clueVitamin to consider
Night blindnessA
Rickets or osteomalaciaD
Hemolysis and neuropathyE
Bleeding with prolonged PTK
Wernicke encephalopathyB1
PellagraB3
Isoniazid-associated neuropathyB6
Megaloblastic anemia with neurologic signsB12
Megaloblastic anemia without typical neurologic signsFolate
Bleeding gums and poor wound healingC

Vitamin D Synthesis

7-Dehydrocholesterol (Skin)
       │  UVB Light (Sunlight)
       ▼
Cholecalciferol (Vitamin D₃)
       │  25-Hydroxylase (LIVER)
       ▼
25-Hydroxyvitamin D₃ / Calcidiol
       │  1-α-Hydroxylase (KIDNEY) [Stimulated by PTH]
       ▼
1,25-Dihydroxyvitamin D₃ / Calcitriol (ACTIVE FORM)

Step 1: Skin Synthesis (Photolysis)

  • Precursor: 7-Dehydrocholesterol (present in the Malpighian layer of the epidermis).
  • Trigger: Ultraviolet B (UVB) radiation from sunlight converts 7-dehydrocholesterol into Pre-vitamin D₃, which isomerizes to Cholecalciferol (Vitamin D₃).
  • (Dietary forms: {D}_3 comes from animal sources; {D}_2 / Ergocalciferol comes from plants/fungi).

Step 2: 1st Hydroxylation — LIVER (Storage Form)

  • Location: Liver (Hepatocytes).
  • Enzyme: 25-Hydroxylase (CYP2R1).
  • Product: 25-Hydroxyvitamin {D}_3 [25-(OH){D}_3] — also known as Calcidiol.
  • MCQ Note: Calcidiol is the major circulating & storage form used to measure serum Vitamin D levels in clinical blood tests.

Step 3: 2nd Hydroxylation — KIDNEY (Active Form)

  • Location: Kidney (Proximal Convoluted Tubule cells).
  • Enzyme: 1-alpha-Hydroxylase (CYP27B1).
  • Product: 1,25-Dihydroxyvitamin {D}_3 [1,25 {-(OH)}_2 {D}_3] — also known as Calcitriol (the physiologically active hormone).

Regulation of 1-alpha-Hydroxylase (High-Yield MCQ Points):

  • Stimulated by:
    • PTH (Parathyroid Hormone) — released during low plasma {Ca}^2+
    • Hypophosphatemia (low serum Phosphate)
  • Inhibited by:
    • High serum Calcium
    • High serum Phosphate
    • FGF-23 (Fibroblast Growth Factor 23)
    • High levels of Calcitriol itself (Negative feedback)