*B1

*Water-soluble

*Whole (unrefined), enriched or fortified grains

*Yeast

*Wheat germ

*Meat (Pork)

*Legumes

*Nuts

*Green vegetables (peas, asparagus, okra)

*Supplements: thiamin HCL, thiamin nitrate

*In our body, thiamin exists as free thiamin and various phosphorylated forms:

*Thiamin monophosphate (TMP)

*Thiamin pyrophosphate (TPP) or thiamin diphosphate (TDP)

*Thiamin triphosphate (TTP)

*Free form in plants

*~95% of thiamin occurs in phosphorylated form with 80-85% as TPP in animal products

*TPP is hydrolyzed by intestinal phosphatases to free thiamin b4 absorption

*Absorption rate from foods is high

*Anti-thiamin factors:

*Thiaminases- cleave thiamin, make it inactive (raw fish, shellfish) (thermolabile- cooking inactivates it so thiamin can be absorbed)

*Thiamin antagonists- inactivate thiamin by oxyreductive process (caffeine and tannic acid) (thermostable)

*Free thiamin absorbed in small intestine

*Low concentrations: active transport (ThTr1 and ThTr2 found in variety of tissues: thiamin/H+ antiport carrier system)

*At high concentrations: passive diffusion

*Transport across basolateral membrane: thiamin/H+ antiport system

*In the blood, 90% of thiamin is transported by RBCs

*Once in RBC, thiamin is phosphorylated to TPP

*Remaining 10% is found as free thiamin bound to albumin or as TMP

*Little storage, most is functional

*Half is in skeletal muscle

*Excess thiamin, TPP, TMP are excreted either intact or catabolized for urinary excretion

*Methylene bridge btwn pyrimidine and thiazole is catabolized generating metabolites

*Coenzyme function

-Energy transformation

-Synthesis of pentoses and NADPH

*Noncoenzyme function

-TPP is important in membrane and nerve conduction: important in transmission of Na+/K+ channels and aCH receptors

*TPP functions in energy transformation as a coenzyme with:

-Pyruvate DH

-Alpha-KG DH

-BC alpha-KA DH

-Transketolases (for NADPH and pentose synthesis)

*Thiamin catalyzes the oxidative decarboxylation rxns for:

Pyruvate DH, alpha-KG DH, BC alpha-KAD

*ATP synthesis and Acetyl CoA needed for FA and cholesterol synthesis is decreased

*Accumulation of pyruvate, alpha-KG, and BCAAs in blood

*This accumulation can lead to ketoacidosis 

*Because that's where BCAA are metabolized

*Skeletal Muscle is very metabolically active (PDH, TCA need Thiamin)

Synthesis of Pentoses and NADPH

*TPP is a coenzyme for transketolase

*A key enzyme in PPP- necessary for making ribose and regenerating NADPH

*RDA Men: 1.2mg/d

*RDA Women: 1.1mg/d

*Determined:

-RDA= EAR + 20%

*Men have more muscle, are more metabolically active

*Erythrocyte transketolase activity:

-Stimulate activity by adding the substrate ribose-5-p or xyulose-5-p w/ or w/o thiamin

-If an increase in enzymatic activity by >25% with thiamin supplementation = deficiency

*Blood pyruvate, alpha-KG, or thiamin

*Thiamin in urine

*Early symptoms= vague

-Fatigue, irritability, poor memory, loss of appetite, sleep disturbances, abdominal discomfort, weight loss

*As deficiency worsens

-Cardiovas sys and neurological symptoms

*Dry, Wet, Acute

*Found mostly in older adults bc of chronic low thiamin intakes

*Nerve and muscle abnormalities

-Prickling sensation in toes

-Burning sensation in feet, leg cramps, pain

-Muscles my become weak and atrophy

*Heart abnormalities 

*Heart pumps more blood and beats faster

-Blood vessels widen= edema in legs/lungs = decrease in blood pressure = shock and death 

*In infants who are breastfed by a mom who has a thiamin def

*Symptoms in baby:

-Anorexia, vomiting, lactic acidosis, altered heart rate, lack of reflexes

*Thiamin def is often associated with alcoholism in western countries:

-Due to decrease in food intake, liver damage and a decrease in thiamin absorption

*Causes brain abnormalities:

-Wernickes: ophthalmoplegia, nystagmus, ataxia

-Korsakoff: loss of short-term memory, confusion

*Ophthalmoplegia: paralysis of ocular muscles

*Nystagmus: constant involuntary eye movement

*Ataxia: impaired muscle coordination

*Low risk of toxicity- due to limit on absorption by brush border

*UL: not established