Thiamine metabolism

Category: biosynthesis

Overview

Thiamine = vitamin B1. Active form: thiamine pyrophosphate (TPP), cofactor for pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (TCA), transketolase (PPP), and branched-chain α-ketoacid dehydrogenase (BCAA catabolism). Deficiency causes: BERIBERI (wet = high-output CHF; dry = peripheral neuropathy) when chronic; WERNICKE encephalopathy (acute confusion + ataxia + ophthalmoplegia) when acute — classic in alcoholism + hyperemesis gravidarum + bariatric surgery + chronic vomiting. Korsakoff syndrome = chronic memory deficit residual to untreated Wernicke. Glucose load WITHOUT thiamine repletion can precipitate Wernicke (the "give thiamine before glucose" ED rule). High-dose IV thiamine (500 mg q8h × 3 days) is first-line treatment.

Organ Systems

• nervous
• digestive

Pathway Steps

1. thiamine → thiamine-pyrophosphate — via thiamine pyrophosphokinase (TPK1). Thiamine pyrophosphokinase activates dietary B1 to thiamine pyrophosphate (TPP), cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase, and transketolase. Deficiency (beriberi, Wernicke-Korsakoff) cripples these enzymes — and a glucose load can precipitate Wernicke in the depleted.

Known Modulators

• riboflavin (cofactor) — vitamin B2 (FMN/FAD precursor). B2; FMN + FAD coenzyme precursor; migraine prophylaxis 400 mg/d
• benfotiamine (substrate) — thiamine (S-acyl prodrug, fat-soluble). lipophilic B1 prodrug; better tissue penetration; diabetic neuropathy supplementation
• sulbutiamine (substrate) — lipophilic B1 prodrug (CNS-penetrant). dimerized lipophilic thiamine; cognitive/asthenia indication in some markets (not US)
• r5p (cofactor) — riboflavin-5-phosphate (active FMN). active phosphorylated B2 form
• thiamine (substrate) — B1 vitamin; TPP cofactor

References

• PMID 20642790