Thiamin

Question 1

What molecules make up thiamin

Answer 1

Pyrimidine + Thiazole

Question 2

Where is the active site ?

Answer 2

Thiazole - C2 (double bond)

Question 3

What is the active form of thiamin

Answer 3

Thiamin pyrophosphate
- addition of 2 phosphates

Question 4

Which element is required in the synthesis of TPP

Answer 4

Mg2+

Question 5

What are the potential outcomes for Free TPP

Answer 5

1. ThTP
   2.AThTP
   3.Bound ThDP
   4.ThMP

Question 6

Metabolic role for Thiamin

Answer 6

Coenzyme in >24 enzymes
Nervous system conduction (conduction and membranes)
Energy production
Biosynthesis of lipids

Question 7

Which Vitamins are Coenzymes

Answer 7

B, C, K

Question 8

Overall the main 3 reactions Thiamin is involved in metabolically can be described as?

Answer 8

1. Oxidative decarboxylation of a-keto acids
2. Transketolation
3. A-oxidation of phytanic acids (b-ox of fat)

Question 9

What is the main job of thiamin in oxidative decarboxylation of alpha-keto acids

Answer 9

To accept and donate acetyl groups

Question 10

TCA cycle

Answer 10

1.Pyruvate to Acetyl-CoA (E1)
2.A-ketoglutarate to Succinyl-CoA

Question 11

Which AA are important for Thiamin and why?

Answer 11

Leucine, isoleucine, valine
TPP dependent Decarboxylation
Without it we get a build of BCAA (keto acids)

Question 12

Describe the 2 parts to transketolase

Answer 12

1. Xylose-5-phosphate transfer to TPP
2. TPP can transfer to Ribose-5P or Erythrose-4P

Question 13

Refsum’s disease

Answer 13

A neurological disorder cause from a build up of phytanic acid because the body cannot break down fat found in meat, dairy, fish

Question 14

Describe absorption of Thiamin

Answer 14

–Not typically absorbed in active form. (broken down to thiamin)
–SLC19A2/3 is the low transporter if >5g it can diffuse
–Enter portal circulation of metabolic trapping via TPK
– Will go to the liver first then other tissues

Question 15

What is the reason why TPK activation metabolically traps thiamin

Answer 15

It converts it to TPP or TMP and the addition of phosphate groups makes the molecules too big for transport

Question 16

Where would you expect most Thiamin in the body?

Answer 16

Muscles - require a lot of energy (50% of body thiamin)

Question 17

Storage

Answer 17

small amount 30mg (80% TPP, 10% TTP, rest as Thiamin & TMP)
– small storage + high metabolic rate means diet intake is necessary

Question 18

Food sources

Answer 18

Plants (synthesize thiamin): whole grains, nuts, bread
Animals (phosphorylated): organ meat, pork, milk, eggs

Question 19

Thiamin can be destroyed by?

Answer 19

Baking soda, UV, Thiaminases, Heat-stable antagonist, Sulfite, Vit C

Question 20

Requirements of Thiamin are Elevated when?

Answer 20

Related to Total energy intake
Elevated in high caloric requirements (infection, dialysis)

Question 21

RDA? UL?

Answer 21

1mg (0.4mg/1000 kcal/day - 2000+kal diet but no less than 1.0mg)
No UL

Question 22

What are the ways to determine status of TPP

Answer 22

Urinary (rough estimate)
Blood pyruvic acid or a-ketoglutarate (not a hard marker)

Question 23

Describe TTP blood test and markers

Answer 23

If activity increase with the added TPP means you are not adequate
A: <15%
M: 16-20%
D: >20%

Question 24

How might poverty lead to a thiamin deficiency?

Answer 24

Reduced intake or having food that has lots of energy but not having enough food that contains the vitamins to acquire the energy

Question 25

Which populations should be concernd for thiamin deficiency?

Answer 25

Low intake
Gi disorders
Increased CHO metabolism
Genetic disorders
Alcoholics (increases calories but not food, gastritis interferes w/absorption, damaged hepatic inhibits activation)

Question 26

Wet Beriberi

Answer 26

Lactic acidosis –> myocardial exhaustion

Plenty of calories, active, but none with the cofactor to break thiamin down, glycolysis is working but no Krebs cycle

Question 27

Dry Beriberi

Answer 27

Neuritic

No calories, not active, no food, myelin degeneration, no thiamin = neurological problems

Can be caused by alcohol

Question 28

Wernicke

Answer 28

Dry Beriberi - Neurological disorder
Double vision, rapid eye movement, ataxia

Question 29

Korsakoff

Answer 29

Dry Beriberi - Psychosis
Memory loss, inability to learn, confusion

Question 30

Bariatric Beriberi

Answer 30

similar to Wernicke
thiamin deficiency caused by decreased food intake and repeated vomiting after surgery