Thiamin B1

active form(s)

TDP (thiamin diphosphate) = TPP (thiamin pyrophosphate). TMP is inactive

enzyme that makes TDP

thiamin pyrophosphokinase (thiamin + ATP → TDP + AMP)

where thiamin is stored

~30 mg total, mostly skeletal muscle, heart, liver, kidney, brain. ~50% in skeletal muscle

3 major roles

energy transformation, sythesis of pentoses and NADPH, nerve conduction

pyruvate dehydrogenase complex rxn 1

oxidative decarboxylation of pyruvate → acetyl CoA

pyruvate dehydrogenase complex rxn 2

3-enzyme complex bound to mitochondrial memberane

what acetyl CoA from PDH is used for

fueling the krebs cycle and synthesizing fatty acids

PDH regulation

substrates activate it. products (acetyl CoA, NADH) inhibit it

a-ketoglutarate dehydrogenase complex rxn

decarboxylation inhibited, so acetyl CoA and succinyl CoA synthesis are inhibited

dry beriberi

affects the nervous system: peripheral neuropathy (paralysis), muscle wasting in the lower extremities, pallor, tachycardia, paresthesias

wet beriberi

affects cardiovascular system: congestive heart failure, edema, tachycardia, cardiomegaly, ECG changes

origin of beriberi

asia in the early 1800s, after rice hulls (main thiamin source) were removed to make white rice

wernicke’s encephalopathy

opthalmoplegia, nystagmus ataxia, loss of memory, confusion

at-risk groups

chronic alcohol users (low intake, damaged liver, decreased absorption), elderly, people with impaired absorption (some cancers, biliary disease, IBD)