Biochemistry chapters
Water-soluble vitamins
Each B vitamin and vitamin C: its active coenzyme form, the reactions it serves, food sources, deficiency disease (beriberi, Wernicke, pellagra, megaloblastic anaemia, subacute combined degeneration, scurvy) and the drugs or conditions that cause deficiency.
- B1 (thiamine) → TPP for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain keto-acid dehydrogenase and transketolase; deficiency (polished rice, alcohol): dry beriberi (neuropathy), wet beriberi (high-output heart failure), Wernicke encephalopathy (confusion, ophthalmoplegia, ataxia: give thiamine before glucose). B3 (niacin) → NAD/NADP; deficiency pellagra (dermatitis, diarrhoea, dementia, death) from maize diets, Hartnup disease, carcinoid syndrome and isoniazid; B6 → PLP for transamination and decarboxylation; deficiency (isoniazid) → neuropathy, seizures, sideroblastic anaemia.
- Folate (THF: one-carbon transfer, DNA synthesis) and B12 (methionine synthase, methylmalonyl-CoA mutase) deficiencies both cause megaloblastic anaemia with raised homocysteine, but only B12 raises methylmalonic acid and causes subacute combined degeneration of the cord; giving folate alone in B12 deficiency can worsen the neurology; folate before conception prevents neural tube defects.
- Vitamin C is needed to hydroxylate proline and lysine in collagen and helps iron absorption; deficiency (scurvy) causes bleeding gums, perifollicular haemorrhages, corkscrew hairs and poor wound healing.
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Overview
Water-soluble vitamins (the B group and vitamin C) act mostly as coenzymes. They are not stored in large amounts (except B12, stored in the liver for several years), so deficiency can appear within weeks to months, and excess is excreted in urine (toxicity is uncommon).
Summary table
| Vitamin | Active form | Main role | Deficiency |
|---|---|---|---|
| B1 Thiamine | Thiamine pyrophosphate (TPP) | Oxidative decarboxylation (pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain keto-acid dehydrogenase); transketolase (pentose phosphate pathway) | Beriberi, Wernicke-Korsakoff |
| B2 Riboflavin | FAD, FMN | Redox (succinate dehydrogenase, electron transport chain, glutathione reductase) | Angular stomatitis, cheilosis, glossitis (magenta tongue), corneal vascularisation, seborrhoeic dermatitis |
| B3 Niacin | NAD⁺, NADP⁺ | Redox (dehydrogenases); made from tryptophan (needs B2, B6) | Pellagra |
| B5 Pantothenic acid | Coenzyme A | Acyl transfer (fatty acid synthesis and oxidation, TCA cycle) | Rare (burning feet) |
| B6 Pyridoxine | Pyridoxal phosphate (PLP) | Transamination, decarboxylation (GABA, serotonin, histamine, dopamine), ALA synthase (haem), glycogen phosphorylase, cystathionine synthase | Peripheral neuropathy, seizures (infants), sideroblastic anaemia, dermatitis, cheilosis |
| B7 Biotin | Biotin | Carboxylations: pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase | Dermatitis, alopecia, enteritis (raw egg whites: avidin binds biotin) |
| B9 Folate | Tetrahydrofolate (THF) | One-carbon transfer: purine and thymidine (DNA) synthesis | Megaloblastic anaemia, neural tube defects |
| B12 Cobalamin | Methylcobalamin, deoxyadenosylcobalamin | Methionine synthase (homocysteine → methionine; regenerates THF), methylmalonyl-CoA mutase | Megaloblastic anaemia, neurological damage |
| C Ascorbic acid | Ascorbate | Hydroxylation of proline and lysine (collagen), dopamine β-hydroxylase, antioxidant, iron absorption (Fe³⁺ → Fe²⁺) | Scurvy |
Thiamine (B1)
Sources: whole grains, pulses, meat; lost in polished rice and by heating.
At-risk groups: alcohol dependence (poor intake and absorption), malnutrition, prolonged vomiting (hyperemesis), refeeding, bariatric surgery, diets of polished rice.
Deficiency:
- Dry beriberi: symmetrical peripheral neuropathy (sensory and motor), muscle wasting.
- Wet beriberi: high-output heart failure (vasodilation), oedema.
- Infantile beriberi: breastfed babies of deficient mothers.
- Wernicke encephalopathy: confusion, ophthalmoplegia (nystagmus, lateral rectus palsy), ataxia; lesions in mammillary bodies and periaqueductal grey. Emergency: IV thiamine.
- Korsakoff syndrome: permanent memory loss with confabulation.
Test: red cell transketolase activity (rises when TPP is added).
Give thiamine before glucose in malnourished or alcohol-dependent patients; glucose alone uses up the remaining thiamine and can precipitate Wernicke encephalopathy.
Niacin (B3)
Sources: meat, fish, peanuts, cereals; also made from tryptophan (about 60 mg tryptophan → 1 mg niacin).
Pellagra: "3 Ds" (dermatitis of sun-exposed skin, including Casal's necklace; diarrhoea; dementia) and a fourth D, death.
Causes: maize-based diets (niacin bound as niacytin, low tryptophan), Hartnup disease (tryptophan not absorbed), carcinoid syndrome (tryptophan diverted to serotonin), isoniazid (B6 deficiency blocks tryptophan → niacin), alcohol.
Pharmacological niacin lowers LDL and triglycerides and raises HDL; adverse effects: flushing (prostaglandins; reduced by aspirin), hyperuricaemia, hyperglycaemia, liver toxicity.
Pyridoxine (B6)
Causes of deficiency: isoniazid, penicillamine, hydralazine, oral contraceptives, alcohol.
Features: peripheral neuropathy, convulsions in infants, sideroblastic anaemia (ALA synthase needs PLP), cheilosis, glossitis, depression.
Large doses cause sensory neuropathy (toxicity possible despite water solubility).
Folate (B9)
Sources: green leafy vegetables, liver, legumes; destroyed by prolonged cooking. Stores last only about 3–4 months.
Causes of deficiency: poor diet (elderly, alcohol), pregnancy and lactation (higher need), haemolytic anaemias (thalassaemia, sickle cell), malabsorption (coeliac disease), drugs: methotrexate, trimethoprim, pyrimethamine (inhibit dihydrofolate reductase), phenytoin, phenobarbitone, valproate, sulfasalazine.
Features: megaloblastic anaemia (macrocytes, hypersegmented neutrophils), glossitis; in pregnancy, neural tube defects in the baby.
Prevention of neural tube defects: 400 micrograms folic acid daily from before conception to 12 weeks; 5 mg daily for high-risk women (previous NTD, epilepsy drugs, diabetes, obesity, sickle cell).
Vitamin B12 (cobalamin)
Sources: only animal foods (meat, fish, eggs, milk); strict vegans risk deficiency. Stores in the liver last 3–5 years.
Absorption: released from food by acid and pepsin → binds R-protein (haptocorrin) → freed by pancreatic enzymes → binds intrinsic factor (from parietal cells) → absorbed in the terminal ileum.
Causes of deficiency:
- Pernicious anaemia (autoimmune: antibodies to intrinsic factor and parietal cells; atrophic gastritis): the commonest cause in many populations.
- Gastrectomy, bariatric surgery.
- Terminal ileal disease or resection (Crohn's disease, TB).
- Fish tapeworm (Diphyllobothrium latum), blind loop (bacterial overgrowth), pancreatic insufficiency.
- Strict vegan diet.
- Drugs: metformin, PPIs, H2 blockers; nitrous oxide (inactivates B12).
Biochemistry:
- Methionine synthase: homocysteine + N⁵-methyl-THF → methionine + THF. Without B12, folate is trapped as N⁵-methyl-THF (folate trap), so DNA synthesis fails → megaloblastic anaemia; homocysteine rises.
- Methylmalonyl-CoA mutase: methylmalonyl-CoA → succinyl-CoA. Without B12, methylmalonic acid rises and abnormal fatty acids enter myelin → neurological damage.
Features: megaloblastic anaemia, glossitis, mild jaundice (ineffective erythropoiesis), subacute combined degeneration of the spinal cord (dorsal columns: loss of vibration and position sense; lateral corticospinal tracts: weakness, extensor plantars with absent ankle jerks), peripheral neuropathy, dementia, optic atrophy.
| Test | Folate deficiency | B12 deficiency |
|---|---|---|
| Homocysteine | ↑ | ↑ |
| Methylmalonic acid | Normal | ↑ |
| Neurological signs | No (except depression) | Yes |
Treating B12 deficiency with folate alone may correct the anaemia but lets the neurological damage progress. Always check and replace B12 first (IM hydroxocobalamin).
Vitamin C
Sources: citrus fruits, guava, amla, tomatoes, green vegetables; destroyed by heat and storage.
Functions: hydroxylation of proline and lysine (prolyl and lysyl hydroxylases) to make stable collagen; iron absorption (reduces ferric to ferrous iron); antioxidant; synthesis of noradrenaline (dopamine β-hydroxylase), carnitine and bile acids.
Scurvy: swollen, bleeding gums, perifollicular haemorrhages, corkscrew hairs, bruising, poor wound healing, anaemia, joint and muscle bleeding; in infants: painful subperiosteal haemorrhage (pseudoparalysis), scorbutic rosary.
Excess vitamin C can promote oxalate kidney stones.
Standard: 400 micrograms = 0.4 mg daily
High risk: 5 mg daily
5 mg ÷ 0.4 mg = 12.5 → the high-risk dose is 12.5 times the standard dose
From 3 months before conception to 12 weeks of pregnancy:
about 6 months ≈ 180 days → 180 tablets of either strength
Expect: coenzyme forms (TPP, FAD, NAD, CoA, PLP, THF, methylcobalamin), enzymes needing thiamine, beriberi and Wernicke-Korsakoff, thiamine before glucose, causes and features of pellagra, isoniazid and B6, biotin and avidin, folate vs B12 deficiency (methylmalonic acid, neurology), causes of B12 deficiency, subacute combined degeneration, folate trap, folic acid in pregnancy, vitamin C and collagen, and scurvy.
Quick revision
- B1 TPP: PDH, α-KGDH, transketolase; beriberi, Wernicke (thiamine before glucose).
- B2 FAD/FMN: angular stomatitis, cheilosis.
- B3 NAD: pellagra (dermatitis, diarrhoea, dementia); maize, Hartnup, carcinoid, isoniazid.
- B6 PLP: transamination; isoniazid neuropathy, sideroblastic anaemia.
- Biotin: carboxylases; raw egg avidin.
- Folate: DNA synthesis; megaloblastic anaemia, NTDs; methotrexate, trimethoprim, phenytoin.
- B12: ↑ MMA and homocysteine; subacute combined degeneration; pernicious anaemia.
- Vitamin C: collagen hydroxylation; scurvy.
Written by The House Job from standard biochemistry references (Lippincott Illustrated Reviews: Biochemistry).
FAQ
Which vitamin deficiency causes Wernicke encephalopathy?
Thiamine (vitamin B1) deficiency, most often in people with alcohol dependence or malnutrition.
What are the features of pellagra?
Dermatitis, diarrhoea and dementia, which can end in death if untreated; it is caused by niacin deficiency.
How can B12 deficiency be distinguished from folate deficiency in the laboratory?
Both raise homocysteine, but only B12 deficiency raises methylmalonic acid.
Why does vitamin C deficiency cause bleeding gums?
Vitamin C is needed to hydroxylate proline and lysine in collagen; without it, collagen is weak and blood vessels and gums bleed easily.