An alcoholic presents with confusion, ataxia, and ophthalmoplegia. Before giving glucose, what must you administer first?
The Pattern
The 3 Dehydrogenases
Five B vitamins feed the same three enzymes. Understand this and you understand half the chapter.
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Three critical dehydrogenases need B1 + B3 + B4 + B5 as cofactors:
1. Pyruvate dehydrogenase (pyruvate → acetyl-CoA)
2. α-ketoglutarate dehydrogenase (TCA cycle)
3. Branched-chain amino acid dehydrogenase
B1 also feeds a 4th enzyme: transketolase (pentose phosphate pathway — used by the brain).
1. Pyruvate dehydrogenase (pyruvate → acetyl-CoA)
2. α-ketoglutarate dehydrogenase (TCA cycle)
3. Branched-chain amino acid dehydrogenase
B1 also feeds a 4th enzyme: transketolase (pentose phosphate pathway — used by the brain).
| Vitamin | Cofactor Form | Pyr DH | α-KG DH | BCAA DH | Other |
|---|---|---|---|---|---|
| B1 Thiamine | TPP | ✔ | ✔ | ✔ | Transketolase |
| B2 Riboflavin | FAD, FMN | ✔ | ✔ | ✔ | ETC complexes I & II |
| B3 Niacin | NAD, NADP | ✔ | ✔ | ✔ | — |
| B4 Lipoic Acid | Lipoamide | ✔ | ✔ | ✔ | — |
| B5 Pantothenic | CoA | ✔ | ✔ | ✔ | Coenzyme A |
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Board trap: The heart needs all 3 dehydrogenases. The brain specifically needs transketolase (B1). That’s why B1 deficiency hits the brain (Wernicke’s) AND heart (beriberi).
The B Vitamins
Tap to Explore Each One
Click any vitamin to reveal its clinical details
B1
Thiamine
TPP • The Brain & Heart Vitamin
Wernicke’s
Enzymes: Pyruvate DH, α-KG DH, BCAA DH + Transketolase
Deficiency — Wernicke’s Encephalopathy:
Classic triad: confusion + ataxia + ophthalmoplegia
Wernicke’s area is in the posterior temporal lobeWernicke’s area is responsible for receiving and understanding spoken/written language. Damage causes receptive aphasia — the patient speaks fluently but makes no sense.
Classic triad: confusion + ataxia + ophthalmoplegia
Wernicke’s area is in the posterior temporal lobeWernicke’s area is responsible for receiving and understanding spoken/written language. Damage causes receptive aphasia — the patient speaks fluently but makes no sense.
Progression → Wernicke-Korsakoff:
Mamillary bodies involved → confabulation (making up memories) + can’t convert short-term to long-term memory
Mamillary bodies involved → confabulation (making up memories) + can’t convert short-term to long-term memory
Beriberi (heart failure):
• Dry beriberi: peripheral neuropathy without heart failure
• Wet beriberi: massive ventricular dilation, pulmonary edema, high-output heart failure
• Dry beriberi: peripheral neuropathy without heart failure
• Wet beriberi: massive ventricular dilation, pulmonary edema, high-output heart failure
CRITICAL: Always give thiamine BEFORE glucose in alcoholics. Glucose metabolism burns through remaining B1 and can precipitate Wernicke’s.
B2
Riboflavin
FAD • FMN
Angular Cheilosis
Role: Makes cofactors FAD and FMN (electron carriers in ETC)
Best source: Milk
Destroyed by: Sunlight (why milk comes in opaque containers)
Deficiency: Angular cheilosis (cracking at corners of mouth) + cheilitis + glossitis
B3
Niacin
NAD • NADH • NADP • NADPH
Pellagra
Cofactors: NAD, NADH, NADP, NADPH
Made from: TryptophanTryptophan can be used to make either serotonin OR niacin. In carcinoid syndrome, serotonin is overproduced, using up tryptophan and causing niacin deficiency (pellagra).
Deficiency — Pellagra (the 4 D’s):
🔑The 4 D’s: Diarrhea, Dermatitis, Dementia, Death
• Diarrhea • Dermatitis (photosensitive, sun-exposed areas) • Dementia • Death
• Diarrhea • Dermatitis (photosensitive, sun-exposed areas) • Dementia • Death
Also caused by:
• Hartnup disease — defective renal transport of tryptophan (leaks into urine, can’t make niacin)
• Carcinoid syndrome — tumor uses up tryptophan making serotonin
• Hartnup disease — defective renal transport of tryptophan (leaks into urine, can’t make niacin)
• Carcinoid syndrome — tumor uses up tryptophan making serotonin
Clinical use of niacin:
• Blocks VLDL production → treats hypertriglyceridemia
• Best drug for raising HDL (45% increase)
• Side effects: flushing (prostaglandins → mast cell degranulation → histamine). Prevent with aspirin/NSAIDs. Treat with antihistamines
• Also: insulin resistance, gout (competes with uric acid excretion)
• Blocks VLDL production → treats hypertriglyceridemia
• Best drug for raising HDL (45% increase)
• Side effects: flushing (prostaglandins → mast cell degranulation → histamine). Prevent with aspirin/NSAIDs. Treat with antihistamines
• Also: insulin resistance, gout (competes with uric acid excretion)
B4
Lipoic Acid
Lipoamide
No deficiency
Enzymes: Same 3 dehydrogenases (pyruvate DH, α-KG DH, BCAA DH)
Deficiency: None clinically significant
Board relevance: low. Just know it feeds the 3 dehydrogenases.
B5
Pantothenic Acid
Coenzyme A
No deficiency
Enzymes: Same 3 dehydrogenases + Coenzyme A (central to all of metabolism)
Deficiency: None clinically significant ("pantothenic" = "everywhere")
Board relevance: low. Know it makes CoA.
B6
Pyridoxine
Pyridoxal Phosphate (PLP)
Neuropathy
Roles: Makes heme (ALA synthase) • Needed by all transaminasesAST and ALT both require pyridoxal phosphate (PLP) as a cofactor. This is why severe B6 deficiency can affect liver enzyme measurements. • Neurotransmitter synthesis
Cofactor form: Pyridoxal phosphate (PLP)
Depleted by: INH (isoniazid) — TB drug pulls B6 out of the body. Always co-prescribe B6 with INH.
Deficiency: Peripheral neuropathy • Sideroblastic anemia (can’t make heme) • Seizures in infants
B9
Folate
Tetrahydrofolate (THF)
Megaloblastic Anemia
Duration: Lasts only 24 hours — first vitamin to run out when cells are rapidly dividing
Role: Makes THF → thymidine → DNA synthesis
Deficiency:
• Megaloblastic anemia + hypersegmented neutrophilsThe cytoplasm divided normally but the nucleus couldn’t (needs DNA) — so it tried and formed extra segments. >5 lobes = hypersegmented. This finding is shared with B12 deficiency.
• Neural tube defects in fetuses (spina bifida, anencephaly)
• Most common cause: overcooked vegetables (heat destroys folate)
• Megaloblastic anemia + hypersegmented neutrophilsThe cytoplasm divided normally but the nucleus couldn’t (needs DNA) — so it tried and formed extra segments. >5 lobes = hypersegmented. This finding is shared with B12 deficiency.
• Neural tube defects in fetuses (spina bifida, anencephaly)
• Most common cause: overcooked vegetables (heat destroys folate)
When are cells dividing most rapidly? 1. Pregnancy, 2. Age 0-2, 3. Age 4-7, 4. Puberty
B12
Cobalamin
Cyanocobalamin
Megaloblastic + Neuro
Duration: Lasts 6-9 months in the liver (acts fat-soluble despite being water-soluble)
Enzymes:
• Homocysteine methyltransferase (also needs folate → makes THF)
• Methyl malonyl-CoA mutase (recycles odd-chain fatty acids → myelin)
• Homocysteine methyltransferase (also needs folate → makes THF)
• Methyl malonyl-CoA mutase (recycles odd-chain fatty acids → myelin)
Absorption: Needs intrinsic factorMade by parietal cells in the stomach. Binds B12 in the duodenum, and the complex is absorbed in the terminal ileum. Pernicious anemia = autoimmune destruction of parietal cells = no IF = no B12 absorption. (from parietal cells) → absorbed in terminal ileum
Deficiency:
• Megaloblastic anemia + hypersegmented neutrophils (same as folate)
• PLUS neurological symptoms: subacute combined degeneration (posterior columns + lateral corticospinal tracts) → loss of proprioception, ataxia, spastic paresis
• ↑ Methylmalonic acid (distinguishes B12 from folate deficiency)
• Megaloblastic anemia + hypersegmented neutrophils (same as folate)
• PLUS neurological symptoms: subacute combined degeneration (posterior columns + lateral corticospinal tracts) → loss of proprioception, ataxia, spastic paresis
• ↑ Methylmalonic acid (distinguishes B12 from folate deficiency)
Causes: Pernicious anemia, vegan diet, Crohn’s/ileal resection, Diphyllobothrium latumFish tapeworm — competes with the host for B12 absorption. Classic board question: immigrant who eats raw freshwater fish develops megaloblastic anemia. (fish tapeworm), metformin
C
Vitamin C
Ascorbic Acid
Scurvy
Role: Collagen synthesis (hydroxylationVitamin C is the cofactor for prolyl hydroxylase and lysyl hydroxylase, which convert proline and lysine residues into hydroxyproline and hydroxylysine in collagen. Without these steps, collagen can’t form stable triple helices. of proline & lysine) • Iron absorption (keeps Fe in Fe²⁺ form) • Antioxidant
Deficiency — Scurvy:
• Weak collagen → bleeding gums, loose teeth, poor wound healing
• Perifollicular hemorrhages, corkscrew hairs
• Easy bruising, petechiae
• Subperiosteal hemorrhage in children
• Weak collagen → bleeding gums, loose teeth, poor wound healing
• Perifollicular hemorrhages, corkscrew hairs
• Easy bruising, petechiae
• Subperiosteal hemorrhage in children
At-risk: Elderly, alcoholics, anyone not eating fruits/vegetables • Also: smokers (increased oxidative stress burns through Vitamin C faster)
Excess: Kidney stones (oxalate), diarrhea, false-negative guaiac test
High-Yield Comparison
Folate (B9) vs B12
Both cause megaloblastic anemia. The board WILL ask you to tell them apart.
| Feature | B9 (Folate) | B12 (Cobalamin) |
|---|---|---|
| Duration in body | 24 hours | 6-9 months |
| Megaloblastic anemia | ✔ | ✔ |
| Hypersegmented neutrophils | ✔ | ✔ |
| Neurological symptoms | ✘ No | ✔ Yes (subacute combined degeneration) |
| Methylmalonic acid | Normal | ↑ Elevated |
| Homocysteine | ↑ Elevated | ↑ Elevated |
| Common causes | Overcooked vegetables, pregnancy, alcoholism | Pernicious anemia, vegan diet, ileal disease |
| Neural tube defects | ✔ Yes | ✘ No |
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The distinguisher: If a patient has megaloblastic anemia + neurological symptoms (numbness, ataxia, proprioception loss), it’s B12. Confirm with ↑ methylmalonic acid. Folate deficiency does NOT cause neuro symptoms.
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