Thiamin Flashcards
What molecules make up thiamin
Pyrimidine + Thiazole
Where is the active site ?
Thiazole - C2 (double bond)
What is the active form of thiamin
Thiamin pyrophosphate
- addition of 2 phosphates
Which element is required in the synthesis of TPP
Mg2+
What are the potential outcomes for Free TPP
- ThTP
2.AThTP
3.Bound ThDP
4.ThMP
Metabolic role for Thiamin
Coenzyme in >24 enzymes
Nervous system conduction (conduction and membranes)
Energy production
Biosynthesis of lipids
Which Vitamins are Coenzymes
B, C, K
Overall the main 3 reactions Thiamin is involved in metabolically can be described as?
- Oxidative decarboxylation of a-keto acids
- Transketolation
- A-oxidation of phytanic acids (b-ox of fat)
What is the main job of thiamin in oxidative decarboxylation of alpha-keto acids
To accept and donate acetyl groups
TCA cycle
1.Pyruvate to Acetyl-CoA (E1)
2.A-ketoglutarate to Succinyl-CoA
Which AA are important for Thiamin and why?
Leucine, isoleucine, valine
TPP dependent Decarboxylation
Without it we get a build of BCAA (keto acids)
Describe the 2 parts to transketolase
- Xylose-5-phosphate transfer to TPP
- TPP can transfer to Ribose-5P or Erythrose-4P
Refsum’s disease
A neurological disorder cause from a build up of phytanic acid because the body cannot break down fat found in meat, dairy, fish
Describe absorption of Thiamin
–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
What is the reason why TPK activation metabolically traps thiamin
It converts it to TPP or TMP and the addition of phosphate groups makes the molecules too big for transport
Where would you expect most Thiamin in the body?
Muscles - require a lot of energy (50% of body thiamin)
Storage
small amount 30mg (80% TPP, 10% TTP, rest as Thiamin & TMP)
– small storage + high metabolic rate means diet intake is necessary
Food sources
Plants (synthesize thiamin): whole grains, nuts, bread
Animals (phosphorylated): organ meat, pork, milk, eggs
Thiamin can be destroyed by?
Baking soda, UV, Thiaminases, Heat-stable antagonist, Sulfite, Vit C
Requirements of Thiamin are Elevated when?
Related to Total energy intake
Elevated in high caloric requirements (infection, dialysis)
RDA? UL?
1mg (0.4mg/1000 kcal/day - 2000+kal diet but no less than 1.0mg)
No UL
What are the ways to determine status of TPP
Urinary (rough estimate)
Blood pyruvic acid or a-ketoglutarate (not a hard marker)
Describe TTP blood test and markers
If activity increase with the added TPP means you are not adequate
A: <15%
M: 16-20%
D: >20%
How might poverty lead to a thiamin deficiency?
Reduced intake or having food that has lots of energy but not having enough food that contains the vitamins to acquire the energy
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)
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
Dry Beriberi
Neuritic
No calories, not active, no food, myelin degeneration, no thiamin = neurological problems
Can be caused by alcohol
Wernicke
Dry Beriberi - Neurological disorder
Double vision, rapid eye movement, ataxia
Korsakoff
Dry Beriberi - Psychosis
Memory loss, inability to learn, confusion
Bariatric Beriberi
similar to Wernicke
thiamin deficiency caused by decreased food intake and repeated vomiting after surgery
