Thiamin (4 questions)

Question 1

What is the main coenzyme form of thiamin?

Answer 1

Thiamine diphosphate = TPP = thiamin pyrophosphate

Question 2

What are the main food sources for thiamin?

Answer 2

1. Fortified breakfast cereals
2. Enriched grains
3. Pork chop
4. Trout

Natural sources are meats/fish

Fortified sources are breads, cereals, infant formulas

Question 3

(T/F) Thiamin can be lost in fluid from cooking if fluid is discarded and not consumed.

Answer 3

TRUE

Question 4

Where is thiamin absorbed? How?

Answer 4

S.I. via active and passive transport (pharmacological doses)

Question 5

What are the 2 transporters that aid in thiamin absorption?

Answer 5

THTR1 = lower affinity transporter

THTR2 = higher affinity transporter; ubiquitously expressed

Question 6

(T/F) Expression of the thiamine transporters are negatively impacted by alcohol intake.

Answer 6

TRUE; THTR1 and THTR2

Question 7

How is thiamin transported in the blood?

Answer 7

Bound to albumin

Question 8

Where is thiamin mainly stored?

Answer 8

The liver

Question 9

Thiamin pyrophosphokinase

Answer 9

Catalyzes the reaction: thiamin + ATP —-> ThDP or TPP in the LIVER

Aka phosphorylates free thiamin (adds Phosphate group) to form TPP

Question 10

(T/F) Plant sources of thiamine are in free form, so it can be absorbed without having to have the phosphate groups cleaved off.

Answer 10

TRUE

Question 11

How does thiamin play a VERY important role in the pyruvate decarboxylation? aka converting pyruvate —> acetyl-CoA

Answer 11

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

Question 12

Why is the reaction of oxidative decarboxylation of pyruvate important?

Answer 12

It is important for generating NADH, FADH (ATP), acetyl-CoA (can enter Kreb’s Cycle or be used to synthesize FAs or cholesterol).

Question 13

What are the 4 important functions of TPP?

Answer 13

1. Pentose Phosphate Pathway
2. Conversion of pyruvate to acetyl-CoA
3. Conversion of alpha-ketoglutarate to succinyl-CoA
4. BCAA metabolism

Question 14

In regards to the conversion of alpha-ketoglutarate —-> succinyl-CoA, how is TPP involved?

Answer 14

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

Question 15

Why is the reaction of alpha-ketoglutarate —> succinyl-CoA important?

Answer 15

It is important for generating NADH and succinyl-CoA

Question 16

In what ways can succinyl-CoA function after being synthesized from alpha-ketoglutarate?

Answer 16

It can go on to:

1. Kreb Cycle intermediate (RATE LIMITING STEP IN CYCLE)
2. Prophyrin / heme synthesis
3. Ketone metabolism

Question 17

How is TPP involved in the Pentose Phosphate Pathway?

Answer 17

TPP is a CoE. for transketolase, which is needed for the PPP.

Question 18

Why is the PPP important?

Answer 18

1. Major source of NADPH (reductive biosynthesis of FAs and cholesterol; the reduction of glutathione)
2. Needed for the biosynthesis of RIBOSE-5-PHOSPHATE (nucleic acid; essential for DNA and RNA synthesis)

Question 19

Transketolase

Answer 19

Dependent on TPP within the PPP

Question 20

How is TPP involved in BCAA metabolism?

Answer 20

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).

Question 21

What are the 3 BCAAs?

Answer 21

Leucine

Isoleucine

Valine

Question 22

(T/F) Alpha keto acids can be cytotoxic in the brain.

Answer 22

TRUE

Question 23

Maple Syrup Urine Disease

Answer 23

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

Question 24

(T/F) Pharmacological doses of thiamin may be beneficial in moderate mutations.

Answer 24

TRUE

Question 25

Thiamine deficiency

Answer 25

BERIBERI

Question 26

Dry Beriberi

Answer 26

Mainly affects lower limbs (nervous system, polyneuritis)

“Burning feet,” weakness, cramps, muscle pain

Question 27

Wet Beriberi

Answer 27

More rare, in addition to dry beriberi symptoms, results in CHF

–edema, pulmonary HTN, lactic acidosis

Question 28

(T/F) Rapid administration of thiamine treats wet and dry beriberi.

Answer 28

TRUE

Question 29

What condition is a result of thiamin deficiency related to chronic alcohol abuse?

Answer 29

Wernicke-Korsakoff Syndrome; resulting in severe brain impairment (encephalopathy)

Can be reversed with the thiamin administration

Question 30

Besides alcohol abuse, what conditions can also cause Wernicke-Korsakoff Syndrome?

Answer 30

Gastrectomy patients

Individuals with rapidly growing hepatic tumors

Drug abuse

AIDS patients

Question 31

Who else is at risk for thiamin deficiency?

Answer 31

Individuals with marginal intake and using diuretics, OR kidney failure

Question 32

In terms of treating thiamine deficiency, what should come first? Thiamin replacement or glucose administration?

Answer 32

Thiamin replacement, and then glucose administration, as thiamine requirements increase with carbohydrate intakes

Question 33

(T/F) Thiamin toxicity is common.

Answer 33

FALSE, rare

Question 34

What is the best method for assessing thiamin status?

Answer 34

Whole Blood TPP

Fasting required because it’s involved in energy metabolism

Normal values: 70-180 nmol/L

Question 35

What measurement may be used in the research setting to assess longer-term status of thiamin?

Answer 35

Erythrocyte transketolase activity; 120 days

Indirect measurement, not recommended for clinical settings due to high variability of assay