Thiamine Review

THIAMINE - VITAMIN B1

Structure:

• Pyrimidine ring
• Thiazole moiety
• Sulfur bridge

SOURCES:

DIGESTION, ABSORPTION, METABOLISM, and EXCRETION

Phosphorylated forms must be digested

Absorption is efficient

• Inhibited by etoh
• Antithiamin factors occur in raw fish, coffee, tea
• Vitamin C prevents thiamine destruction

Re-phosphorylation occurs in gut or liver cells

Blood cells take up and phosphorylate circulating B1

Retention in tissues is limited

• 1/2 life is less than 3 weeks

Excreted in urine

FUNCTION/MOA

Thiamine has ESSENTIAL COENZYME and NON-COENZYME ROLES

• Energy production and nutrient metabolism
• Coenzyme roles in pyruvate dehydrogenase
• a-keogluterate deyhyrogenase
• Branched chain a-keto-acid dehydrogenase complexes
• Nutrient metabolism
• Inter conversion of phosphoylated sugars for the syntheses of nucleotides and some B-vitamin coenzymes (like transketolase)
• Nervous system functions (nonconenzyme)

CO-ENZYME ROLES

Energy Production and Nutrient Metabolism

• Energy transformation (coenzyme role)
• Pyruvate dehydrogenase complex
• 3 enzymes make up this complex
• 4 vitamins are needed: TDP, FAD, NAD, CoA
• Also: ATP and magnesium
• Alpha-ketoglutarate dehydrogenase complex
• Branched chain alpha-ketoacid dehydrogenase complex
• Failure to oxidize ~ Maple Syrup Urine Disease
• LIV if you hang from a BRANCH
  Leucine Isoleucine Valine are Branched Chain Amino Acids

• Reductions or inhibitions 
• Diminished synthesis of ATP
• Impaired synthesis of Ach
• Impaired synthesis of fatty acids, cholesterol
• Accumulation of:
• Pyruvate
• Lactate
• a-ketogluterate

Nutrient Metabolism - Interconversion of Phosphorylated Sugars

• TDP also functions as Transketolase, a key enzyme in the Pentose phosphate pathway for pentose and NADPH production.

• 5- Carbon Sugars: ribose

NON-CO-ENZYME ROLES: NERVOUS SYSTEM FUNCTIONS

Role in regulating Sodium Channels

Production of Ach

Membrane and nerve conduction (non-coenzyme role)

TREATMENT ROLES: MSUD: 100mg+

METABOLISM AND EXCRETION

Urinary excretion

RDA

1.2 mg per day men 1.1 mg women

DEFICIENCY

Deficiency impacts energy production

Few weeks to months of inadequate diet

Initial: fatigue, nausea

Dry Beri Beri - neuropathy, muscle weakness, cramping

Wet Beri Beri - cardiomegaly, tachycardia, edema

Acute Beri Beri - nausea vomiting lactic acidosis

RX: 30 mg TID mild, 100-800 mg daily

Risk: etoh, older, malabsorption

TOXICITY

No TUL

ASSESSMENT

Thiamine and/or TDP in blood or urine

Erythrocyte tranketolase activity in hemolyzed whole blood