Thiamin Flashcards
What are the properties of thiamin?
- colorless
- water-soluble
- Unstable in UV light, moisture, alkaline/neutral solutions.
What type of solution does thiamin require to remain stable?
acid solution
What 2 compounds is thiamin made up of and which one contains the active site?
Pyrimidine and thiazole, the thiazole contains the active site
What is the active/coenzyme form of thiamin?
ThDP or TPP (thiamin di/pyro-phosphate)
What enzyme converts thiamin into ThDP?
Thiamin pyrophosphokinase
why is there both free and bound ThDP?
Once TPP or ThDP is activated, it can now be bound to enzymes to play its role in reactions.
What metabolic functions does thiamin play a role in?
- Nervous system function (nerve conduction & neural membranes)
- Energy production
- Biosynthesis of lipids
Specifically what reactions does thiamin play a role in in central metabolism? And what enzymes is it a coenzyme for in this regard?
Oxidative decarboxylation of alpha-keto acids.
PDC, a-ketoglutarate dehydrogenase, and branched-chain a-keto acid decarboxylase
What reaction does TPP assist in with the PDC?
Decarboxylation of pyruvate (1st step)
What role does TPP play in regards to branched chain AAs?
It is the coenzyme for a-keto acid decarboxylase.
It helps in the conversion of the keto acids after deamination into acetyl-CoA or Succinyl-CoA
What happens to the branched chain AA conversion when their is insufficient thiamin?
Would get a build up of the intermediates/keto acids and wont be able to convert into substrates for metabolism.
Metabolic acidosis
What is transketolation? And what pathway is it involved in?
The interconversion of sugar phosphates in pentose sugar shunt.
Pentose Phosphate pathway (G6P –> R5P and NADPH)
What is TPPs role in transketolation and with transketolase?
- Can pick up a keto group from one sugar molecule in one reaction and give it to another in a different reaction.
- Can also aid in transketolase shifting sugar carbons around between 2 molecules to produce what’s needed at that time.
Other than its role in oxidative decarboxylation and transketolation, what does thiamin play a role in regarding metabolism?
alpha-oxidation of phytanic acid (found in meat, dairy and fish).
Thiamin is needed for the proper metabolism of 3-methyl-substituted FA
What 3 AAs does TPP assist in the metabolism of?
Leucine, isoleucine, and valine
What is Refsum’s Disease?
Where there is a build up of phytanic disease. Can result from genetic enzyme disorders.
Briefly explain how thiamin is absorbed.
- converted from phosphorylated form into thiamin.
- taken up my enterocytes by either carrier-mediated transport (intake low) or through diffusion (high intake)
- metabolically trapped/phosphorylated
Why is metabolic trapping important?
- traps it in the cell
- Activates the coenzyme
- maintains the gradient
Where is thiamin stored in the body and how much?
Only small amount stored (30mg)
most in skeletal muscle (50%) + liver, kidney, and nervous system.
80% TPP, 10% TTP, rest as thiamin and TMP
How does metabolic rate influence thiamin storage and why?
Higher metabolic rate causes lower storage since more thiamin is required in metabolic reactions (being used up faster).
Briefly describe control of thiamin renal reabsorption. And how intake influences it.
reabsorbed in renal BBM via saturable carrier-mediated transport.
Excess intake (more than what tissues need) results in rapid excretion.
Where in the body can thiamin be produced?
The gut microflora can produce several metabolites.
Note: animals cannot make thiamin, only plants and some microorganisms
What are 2 plant and animal sources of thiamin?
Plant - whole grains, nuts
Animal (mainly phosphorylated forms) - organ meat, milk
What can cause loss of thiamin in foods?
- Boiling/blanching (want to minimize water used in cooking)
- Baking soda
- UV
- thiaminases (raw freshwater fish, shellfish, ferns)
- Heat-stable antagonist (caffeic and tannic acid)
- Sulfite (preservative in processed foods)
What influences individual thiamin requirements?
- Total energy intake - since involved in metabolism of CHO, protein and lipids.
- May be increased in those with high caloric requirements (chronic infection, patients on dialysis)
- requirements may be altered by thiaminases, thiamin antagonists, and vitamin c
How does vitamin C affect thiamin requirements?
Vit C may counteract the anti-thiamin affects of tannic acid
What are the thiamin recommendations for intake?
RDA: 0.4mg/1000kcal/day for 2000+ kcal diets BUT no less than 1.0mg
Males >14yrs = 1.2mg/d
Females >19yrs = 1.1mg/d
NO UL (lack of reported adverse effects)
How can thiamin status be determined?
- Urinary excretion
- Blood pyruvic acid/a-ketoglutarate (higher with thiamin deficiency), though very sensitive or specific).
- Transketolase activity
How is thiamin status determined by transketolase activity?
if TPP is added to blood and activity increases, means that blood is NOT saturated with TPP and have insufficient thiamin.
What are the levels of %TPP effect (AC)?
Adequate: <15%
Marginal: 16-20%
Deficient: >20%
What are 4 causes of thiamin deficiency?
- Reduced intake
- Increased consumption rate (high CHO diet, pregnancy, fever, physical activity)
- Increased depletion (diarrhea, dialysis)
- Decreased absorption (chronic intestinal disease, alcoholism, gastric bypass)
What are 5 populations are risk for thiamin deficiency?
- those with low intake (polish rice is main staple, elderly living at home, children with unbalanced diet)
- GI disorders
- genetic disorders (enzyme systems)
- Periods of increased CHO metabolism (preg, lactation, growth)
- Alcoholics (increased calorie intake from alcohol but decreased food intake)
- induces gastritis and damages hepatic functions.
what are the results and symptoms of thiamin deficiency?
- decreased urinary excretion
- decreased erythrocyte transketolase activity
- marginal –> usually see symptoms after 21-28 days of inadequacy (tired, irritable, depression, loss of appetite)
- Severe –> Beriberi
what is wet and dry beriberi?
Wet = CV
- lactic acidosis (acumm. of lactic and pyruvic acid leads to edema and causes increased cardiac output / myocardial exhaustion).
- results from severe physical exertion + high CHO intake + chronic thiamin defic.
Dry = neuritic
- peripheral neuropathy – tingling, numbness, weakness.
- myelin degeneration
- due to inactivity + caloric restriction + chronic thiamin defic.
what 2 thiamin deficiency conditions can alcoholism lead to?
Wernicke (neurological disorder - double vision + uncoordinated gait)
and Korsakoff (psychosis/abnormal mental state - memory loss)
