Thiamin: Vitamin B1 Flashcards
thiamin rich foods
grains, proteins, legumes, fruits
active form of thiamin
thiamin pyrophosphate (diphosphate, TPP) or TDP
thiamin has __ activity
thiamin has co-factor activity
thiamin is very stable in __
unstable in __ and __
thiamin is very stable in acid
unstable in base and UV light
thiamin binds __ and converts to __ form
thiamin binds keto-sugar and converts to CoA form
most important biological form of thiamin:
TPP or TDP bc of its co-factor activity
thiamin is destroyed by __ and __
thiamin is destroyed by alkali (pH > 8) and by prolonged heat
__, __, and __ consumption can decrease thiamin availability
raw fish, heme-containing meats, and coffee/tea consumption can decrease thiamin availability
thiaminases exist in __ and function to __
thiaminases exist in 2 isoforms and function to cleave thiamin at methylene bridge
thiaminases are __ and inactivated with __
thiaminases are thermolabile and inactivated with cooking
which thiaminase is more common?
thiaminase 1
thiaminase 1 is mainly present in
freshwater fish and shellfish
thiaminase II is present in
some bacteria and yeast
raw fish contains __ that destroy __
raw fish contains thiaminases that destroy thiamin
OCT aka
organic cation transporter
absorption of thiamin at physiological concentrations: __
inhibited by __
absorption of thiamin at physiological concentrations: Th-Tr mediated
inhibited by alcohol
absorption of thiamin at high concentrations:
passive diffusion
2 main thiamin transporters:
ThTr1 and ThTr2
ThTr1 and ThTr2 are __
they exchange thiamin for __
greatest activity in __
ThTr1 and ThTr2 are antiporters
they exchange thiamin for H+ ions
greatest activity in upper jejunum
ThTr1 expression and capacity
highly expressed in all cells
high capacity
ThTr2 expression and capacity
low capacity, high specificty for thiamin
expression increases in response to LOW thiamin intake
main form of thiamin in portal circulation
free thiamin
thiamin release into circulation
- ThTr2 on basal side of enterocyte pushes thiamin to basal side
- free thiamin goes into portal circulation
thiamin absorption
- TMP, TDP to free thiamin (alkaline phosphatase)
- ThTr1 and 2 on apical surface of enterocyte absorb thiamin
organic cation transporters (OCT) may transport __ thiamin in __
organic cation transporters (OCT) may transport free thiamin in intestine
Defects in __ gene which encodes ThTr1 causes a thiamin responseive deficiency disorder, known as __
Defects in SLC19A2 gene which encodes ThTr1 causes a thiamin responseive deficiency disorder, known as Rogers syndrome
Rogers syndrome, what transporter still works? is it enough?
ThTr2
but it is not enough to do the work of both
~90% thiamin in circulation is in __ as __
~90% thiamin in circulation is in blood cells as TDP
thiamin enters red blood cells by
facilitated diffusion
in peripheral tissues, transport into cells mediated by __ (__) and __ (__)
in peripheral tissues, transport into cells mediated by ThTr1 (free thiamin) and RFC-1 (uptakes TMP, also reduced folate carriers)
mutations in ThTr1 (Rogers syndrome) is characterized by __, __, and __
repsonsive to __
mutations in ThTr1 (Rogers syndrome) is characterized by megaloblastic anemia, sensorineural deafness, and diabetes
repsonsive to thiamin treatment
thiamin is stored mostly in (5)
- liver
- skeletal muscle
- heart
- kidney
- brain
these are high energy tissues, thiamin deficiency = low energy
50% of body’s thiamin is in
muscle
is we consume no thiamin, we notice in __
is we consume no thiamin, we notice in a few weeks
2 types of TDP dependent rxns
- decarboxylation of alpha-ketoacids to acyl-CoA
- interconversion of sugar phosphates
3 decarboxylation rxns requiring TDP
- pyruvate dehydrogenase (TCA)
- alpha-KG dehydrogenase (TCA)
- branched-chain amino acid dehydrogenase
1 interconversion of sugar phosphates rxn
- transketolase (PPP)
TDP-depdendent rxns create __ and __ equivalents for macromolecule synthesis
TDP-depdendent rxns create energy: ATP and reducing equivalents for macromolecule synthesis
inhibition of the TDP requiring rxns leads to accumulation of pyruvate, lactate, and alpha-KG, leading to __
inhibition of the TDP requiring rxns leads to accumulation of pyruvate, lactate, and alpha-KG, leading to acidosis
determining thiamin status
measure RBC transketolase
excess __ causes thiamin deficiency
excess glucose causes thiamin deficiency
why does excess glucose cause thiamin deficiency?
thiamin follows glucose
SO, we supplement thiamin with IV glucose
__ inhibits both thiamin transporters
alcohol
groups at risk for thiamin deficiency
- elderly
- malabsorption
- alcohol (Wernicke-Korsakoff syndrome)
- cancer patients undergoing chemo
- excess glucose infusion
- congestive heart failure
why does excess glucose infusion put you at risk for low thiamin?
thiamin follows glucose
thiamin is involved in rxns that produce glucose
thiamian deficiency
- beri beri
- Wernicke-Korsakoff
dry beri beri
chronic
neuropathies caused by inactivity + calorie restriction + not enough thiamin
wet beri beri
cardiovascular, rapidly fatal (bc cardiac component)
severe physical effort + high carb intake = edema
acute beri beri
infants
anorexia, vomiting
lactic acidosis
heart failure
Wernicke-Korsakoff syndrome
alcohol addiction promotes low __ and __ damage
Wernicke-Korsakoff syndrome
alcohol addiction promotes low thiamin intake and liver damage
Wernicke encephalopahty
ataxia, abnormal motor function, paralysis of eye movements, amnesia, apathy
wernicke-korsakoff treatment?
thiamin supplementation usually helps, but some damage is irreversible
