Thiamin (4 questions) Flashcards
What is the main coenzyme form of thiamin?
Thiamine diphosphate = TPP = thiamin pyrophosphate
What are the main food sources for thiamin?
- Fortified breakfast cereals
- Enriched grains
- Pork chop
- Trout
Natural sources are meats/fish
Fortified sources are breads, cereals, infant formulas
(T/F) Thiamin can be lost in fluid from cooking if fluid is discarded and not consumed.
TRUE
Where is thiamin absorbed? How?
S.I. via active and passive transport (pharmacological doses)
What are the 2 transporters that aid in thiamin absorption?
THTR1 = lower affinity transporter
THTR2 = higher affinity transporter; ubiquitously expressed
(T/F) Expression of the thiamine transporters are negatively impacted by alcohol intake.
TRUE; THTR1 and THTR2
How is thiamin transported in the blood?
Bound to albumin
Where is thiamin mainly stored?
The liver
Thiamin pyrophosphokinase
Catalyzes the reaction: thiamin + ATP —-> ThDP or TPP in the LIVER
Aka phosphorylates free thiamin (adds Phosphate group) to form TPP
(T/F) Plant sources of thiamine are in free form, so it can be absorbed without having to have the phosphate groups cleaved off.
TRUE
How does thiamin play a VERY important role in the pyruvate decarboxylation? aka converting pyruvate —> acetyl-CoA
TPP is a CoE. for PYRUVATE DEHYDROGENASE (a multi-complex enzyme), needed for oxidative decarboxylation of pyruvate
Thiamin transfers the derivative of pyruvate over to the next phase of the enzyme complex. This reaction cannot be carried forward without thiamine
Why is the reaction of oxidative decarboxylation of pyruvate important?
It is important for generating NADH, FADH (ATP), acetyl-CoA (can enter Kreb’s Cycle or be used to synthesize FAs or cholesterol).
What are the 4 important functions of TPP?
- Pentose Phosphate Pathway
- Conversion of pyruvate to acetyl-CoA
- Conversion of alpha-ketoglutarate to succinyl-CoA
- BCAA metabolism
In regards to the conversion of alpha-ketoglutarate —-> succinyl-CoA, how is TPP involved?
TPP is a CoE. for ALPHA-KETOGLUTARATE DEHYDROGENASE (a multi-enzyme complex) needed for oxidative decarboxylation of alpha-ketoglutarate, in the mitochondria.
NOTE: This reaction is coupled with the NAD derivative form of NIACIN
Why is the reaction of alpha-ketoglutarate —> succinyl-CoA important?
It is important for generating NADH and succinyl-CoA
In what ways can succinyl-CoA function after being synthesized from alpha-ketoglutarate?
It can go on to:
- Kreb Cycle intermediate (RATE LIMITING STEP IN CYCLE)
- Prophyrin / heme synthesis
- Ketone metabolism
How is TPP involved in the Pentose Phosphate Pathway?
TPP is a CoE. for transketolase, which is needed for the PPP.
Why is the PPP important?
- Major source of NADPH (reductive biosynthesis of FAs and cholesterol; the reduction of glutathione)
- Needed for the biosynthesis of RIBOSE-5-PHOSPHATE (nucleic acid; essential for DNA and RNA synthesis)
Transketolase
Dependent on TPP within the PPP
How is TPP involved in BCAA metabolism?
TPP is a CoE. for branched-chain alpha-keto acid dehydrogenase (a multi-enzyme complex, needed for oxidative decarboxylation of alpha keto acid from BCAAs, in the mitochondria).
What are the 3 BCAAs?
Leucine
Isoleucine
Valine
(T/F) Alpha keto acids can be cytotoxic in the brain.
TRUE
Maple Syrup Urine Disease
Genetic disease; mutation; not able to metabolize these alpha-keto acids from BCAAs, so they are at very high risk for mental retardation due to the cytotoxic build-ups in the brain
(T/F) Pharmacological doses of thiamin may be beneficial in moderate mutations.
TRUE
Thiamine deficiency
BERIBERI
Dry Beriberi
Mainly affects lower limbs (nervous system, polyneuritis)
“Burning feet,” weakness, cramps, muscle pain
Wet Beriberi
More rare, in addition to dry beriberi symptoms, results in CHF
–edema, pulmonary HTN, lactic acidosis
(T/F) Rapid administration of thiamine treats wet and dry beriberi.
TRUE
What condition is a result of thiamin deficiency related to chronic alcohol abuse?
Wernicke-Korsakoff Syndrome; resulting in severe brain impairment (encephalopathy)
Can be reversed with the thiamin administration
Besides alcohol abuse, what conditions can also cause Wernicke-Korsakoff Syndrome?
Gastrectomy patients
Individuals with rapidly growing hepatic tumors
Drug abuse
AIDS patients
Who else is at risk for thiamin deficiency?
Individuals with marginal intake and using diuretics, OR kidney failure
In terms of treating thiamine deficiency, what should come first? Thiamin replacement or glucose administration?
Thiamin replacement, and then glucose administration, as thiamine requirements increase with carbohydrate intakes
(T/F) Thiamin toxicity is common.
FALSE, rare
What is the best method for assessing thiamin status?
Whole Blood TPP
Fasting required because it’s involved in energy metabolism
Normal values: 70-180 nmol/L
What measurement may be used in the research setting to assess longer-term status of thiamin?
Erythrocyte transketolase activity; 120 days
Indirect measurement, not recommended for clinical settings due to high variability of assay
