Thiamin Flashcards

1
Q

What molecules make up thiamin

A

Pyrimidine + Thiazole

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2
Q

Where is the active site ?

A

Thiazole - C2 (double bond)

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3
Q

What is the active form of thiamin

A

Thiamin pyrophosphate
- addition of 2 phosphates

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4
Q

Which element is required in the synthesis of TPP

A

Mg2+

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5
Q

What are the potential outcomes for Free TPP

A
  1. ThTP
    2.AThTP
    3.Bound ThDP
    4.ThMP
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6
Q

Metabolic role for Thiamin

A

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

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7
Q

Which Vitamins are Coenzymes

A

B, C, K

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8
Q

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

A
  1. Oxidative decarboxylation of a-keto acids
  2. Transketolation
  3. A-oxidation of phytanic acids (b-ox of fat)
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9
Q

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

A

To accept and donate acetyl groups

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10
Q

TCA cycle

A

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

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11
Q

Which AA are important for Thiamin and why?

A

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

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12
Q

Describe the 2 parts to transketolase

A
  1. Xylose-5-phosphate transfer to TPP
  2. TPP can transfer to Ribose-5P or Erythrose-4P
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13
Q

Refsum’s disease

A

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

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14
Q

Describe absorption of Thiamin

A

–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

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15
Q

What is the reason why TPK activation metabolically traps thiamin

A

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

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16
Q

Where would you expect most Thiamin in the body?

A

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

17
Q

Storage

A

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

18
Q

Food sources

A

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

19
Q

Thiamin can be destroyed by?

A

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

20
Q

Requirements of Thiamin are Elevated when?

A

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

21
Q

RDA? UL?

A

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

22
Q

What are the ways to determine status of TPP

A

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

23
Q

Describe TTP blood test and markers

A

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

24
Q

How might poverty lead to a thiamin deficiency?

A

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

25
Which populations should be concernd for thiamin deficiency?
Low intake Gi disorders Increased CHO metabolism Genetic disorders Alcoholics (increases calories but not food, gastritis interferes w/absorption, damaged hepatic inhibits activation)
26
Wet Beriberi
Lactic acidosis --> myocardial exhaustion Plenty of calories, active, but none with the cofactor to break thiamin down, glycolysis is working but no Krebs cycle
27
Dry Beriberi
Neuritic No calories, not active, no food, myelin degeneration, no thiamin = neurological problems Can be caused by alcohol
28
Wernicke
Dry Beriberi - Neurological disorder Double vision, rapid eye movement, ataxia
29
Korsakoff
Dry Beriberi - Psychosis Memory loss, inability to learn, confusion
30
Bariatric Beriberi
similar to Wernicke thiamin deficiency caused by decreased food intake and repeated vomiting after surgery