2. Thiamin, riboflavin, niacin Flashcards
General functions of B vitamins (4)
- micronutrient metabolism
- energy production ATP
- energy release
- carbon metabolism - transfer of single carbon units
Coenzymes
required for the activity of enzymes
enzymes
at as catalysts, drive many reactions and pathways
relation of B vitamins and coenzymes?
part of the “structure” of coenzymes
T/F
B vits work together?
True
Vitamins are involved in Intermediary Metabolism of …? (5)
- Carbs
- Proteins
- Fats
- ATP Generation
- Nucleic Acids/Fatty Acids/Steriods
Carb metabolism pathways vitamins are involved in?
glycolysis and gluconeogenesis
Protein metabolism pathways vitamins are involved in?
Protein synthesis and amino acid oxidation
Fat metabolism pathways vitamins are involved in?
FA synthesis and Beta oxidation
ATP generation metabolism pathways vitamins are involved in?
Respiratory chain and oxidative phosphorylation
Nucleic Acids/Fatty Acids/Steriods metabolism pathways vitamins are involved in?
pentose phosphate pathways
What is added to thiamine to synthesize its coenzyme form?
Phosphates
What is thiamines coenzyme form?
Thiamine pyrophosphate (TPP)
Thiamine’s main metabolic role
- facilitates energy release from foods
- central role in carb metabolism
Reactions thiamine is involved in?
2 types
multiple enzymes
- Oxidative decarboxylations:
- pyruvate dehydrogenase
- alpha-ketoglutarate dehydrogenase - Transketolase Reactions:
- transketolase (requires magnesium)
Thiamines short form?
B1
thiamine requires what other vitamin to perform transketolase reactions?
Magnesium
TCA cycle full name?
Citric Acid Cycle
Thiamine deficiency?
Beri-Beri
Translation of beri-beri?
i can’t i cant
Symptoms of beri beri?
*** anorexia + weight loss
neurological symptoms
paralysis
cardiovasc + resp
What deficiency causes beri-beri?
thiamine
T/F
-disease can’t be reversed
False:
Thiamine reverses disease rapidly
Why is beri beri rare?
Thiamine is fortified in Canadian flour since 1949
What is thiamine fortified in?
Canadian Flour
3 types of beri-beri?
- Wet (edema)
- Dry (no edema)
- Infantile
Symptoms Wet beri-beri (edema)
cardio-resp
- heart swelling
- pulmonary congestion
Symptoms dry beri-beri (no edema)
- central nervous system impairment
- (alcohol - Wernicke-Korsakoff Syndrome)
- confusion, memory loss, confabulation
What does edema mean?
Swelling
What does “confabulation” mean?
memory disturbance
-fabricated, distorted or misinterpreted memories about oneself or the world, without the conscious intention to deceive
Cause of Infantile beri-beri?
Symptoms?
breast fed infants of deficient mothers
- vomiting, diarrhea, convulsions
- aphonia
- sudden death can occur
what is “aphonia” ?
inability to produce voice
Thiamine deficiency has been identified in what major disease? (Why?)
Diabetes
Consider role of thiamine in glucose metabolism
3 benefits of thiamine? (particularly in diabetes patients)
improved glucose metabolism, imflammatory status and vascular function
2 Health claims in Europe regarding thiamine?
- Normal carb and energy-yeilding metabolism
- Maintenance of normal neurological function
Why is riboflavin called B2
2nd B vit discovered
3 forms of riboflavin?
- Riboflavin
- Flavin Mononucleotide FMN (added Phosphate)
- Flavin Adenine Dinucleotide FAD (added phosphate, ribose and adenine)
*FMN and FAD are the coenzyme forms
Riboflavin essential for what conversion?
conversion of B6 to is co-enzyme forms
Riboflavins coenzyme forms?
FMN - Flavin Mononucleotide
FAD - Flavin Adenine Dinucleotide
Riboflavin’s metabolic roles?
accept/donate hydrogen (on OH 3)
- FAD
Flavin-dependent enzymes (flavoproteins)
- Electron Transport Chain (Respiratory Chain)
Riboflavin involvement in TCA cycle?
Relation to the electron transport chain?
TCA Cycle
- FAD accept 2H+ from Succinate –> Fumarate
Electron transport chain
- FADH2 involved with coenzyme Q
Riboflavin involvement in TCA cycle?
Relation to the electron transport chain?
TCA Cycle (OH 1 and 4) - FAD accept 2H+ from Succinate --> Fumarate
Electron transport chain
- FADH2 involved with coenzyme Q
Photolabile
susceptible to change with light
Riboflavin food sources?
Fortified in?
Milk products, liver, meat
fortified flour in Canada
What processing destroys thiamine and riboflavin?
Milling of wheat
True/False
Riboflavin deficiency can be fatal?
False
Deficiency is non specific and never fatal
Symptoms of riboflavin deficiency
lesion symptoms
- cheilosis
- megenta tongue
- angular stomatitis (mouth)
- soborrheic dermatitis (skin)
**What other vitamin could riboflavin def affect?
Iron
Why??
Iron status can be interfered with from what vitamin deficiency
riboflavin
How does riboflavin deficiency affect iron? (2)
- Impairs mobilization of iron from its storage protein (ferritin)
- Impairs iron absorption
Studies of women show correcting a marginal riboflavin deficiency improves _____ status
(other than but related to iron)
hemoglobin status
B3 name
Niacin
Niacins other name
B3
2 chemical structures of niacin?
where are they found
Nicotinic Acid (drug form) Nicotinimide (major blood circulating form)
2 Co-enzyme forms of niacin?
NAD(H) - Nicotinamide adenine dinucleotide
NADP(H)
Where does the action occur for the coenzymes of Niacin?
at the Nitrogen
Niacin can be synthesized from what amino acid?
tryptphan
What ratio is niacin synthesized from tryptophan?
60mg tryptophan = 1mg of niacin
What macronutrient must be considered when calculating niacin intake?
Protein
- niacin can be synthesized from the amino acid tryptophan
meaning of Niacin Equivalent?
units used to express niacin content of food. It represents preformed niacin plus tryptophan equivalents (60 mg tryptophan = 1 mg niacin).
Kynurinine Pathway
a metabolic pathway leading to the production of nicotinamide adenine dinucleotide (NAD+) from the degradation of the essential amino acid tryptophan
What is the key intermediate in kynurenine pathway
kynurenine
What vit(s) are needed in the Kynurinine Pathway?
riboflavin + B6
Does Kynurinine Pathway produce enough niacin?
No, niacin still essential in the diet
- completely replaces need in rodents dogs and pigs
Major steps and vitamins involved in the Kynurinine Pathway
Tryptophan –> Kynurine –> NAD/NADP
riboflavin and B6 needed for Kynurine –> NAD/NADP
Metabolic role of niacin (3)
- macronutrient metabolism
- transfers hydrogen during metabolic reactions
- oxidation/reduction reactions
How many enzyme is niacin involved with?
Atleast 200
Where is niacin used in the TCA cycle?
all NAD+ –> NADH+H+
- ** Pyruvate –> Acetyl CoA
2/3. Isocitric Acid –> alpha ketoglutaric acid –> succinyl-Coa
- Malic Acid –> Oxaloacetic Acid
(final step, re-enters TCA cycle)
Niacin in the Electron Transport Chain?
10 NADH enter the start from 1 molecule of glucose
Decarboxylation reactions:
2 NADH glucose–> pyretic acid (Glycolysis)
2 NADH pyruvate –> acetyl CoA
6 NADH (TCA cycle)
Niacin in Glycolysis/Gluconeogenesis
Glycolysis:
Glyceraldehyde-3-phosphate –> 1,3 Biphosphoglycerate
NAD+ –> NADH+H+
Gluconeogenesis:
reverse
Niacin in Pentose Phosphate Pathway
Glucose-6-phosphate –> Ribose-5-phosphate
2x NADP –> NADPH + H+
2 purposes of the pentose phosphate pathway?
- generate “NADPH” used for synthesis of “FA and steroids”
2. generate “ribose” for synthesis of “nucleic acids”
Oxidation means hydrogen ______ ?
Acceptor
ex. NAD(P) –> NAD(P)H
Reduction means hydrogen ______?
Donor
ex. NAD(P)H –> NAD(P)
Niacin “oxidation” is used for the metabolism of? (4)
NAD(P) –> NAD(P)H
Pyruvate, TCA intermediates, glycolysis intermediates, pentose phosphate pathway
Niacin “reduction” is used for?
NAD(P)H –> NAD(P)
Reductive biosynthesis of fatty acids and steroids
Where is NADPH generated?
Pentose Phosphate Pathway
Pellagra is italian for?
rough skin
What disease is associated with Niacin deficiency
pellagra
Pellagra is associated with a deficiency of what vitamin
Niacin (B3)
Symptoms of pellagra
4 D’s
- diarrhea
- dermatitis
- dementia
- death
*case study OH 7
Hartnup’s Disease
Improved with?
- Autosomal recessive disorder
- Develop pellagra (niacin deficiency) due to defect in absorption process for Tryptophan
improved with nicotinamide treatment
Causes of pellagra symptoms in absence of dietary niacin deficiency? (2)
- Isoniaizid; prolonged treatment (drug competes with B6, needed in the Kururenine pathway)
- Hartnup’s Disease (autosomal recessive disorder, defect in tryptophan absorption)
Problem with niacin in corn?
How to fix it?
Niacin bond and unavailable
- also low in tryptophan
Alkali treatment (ex. lime water) breaks bond
Niacin requirement is expressed as?
Niacin Equivalent (NE)
Niacin (Nicotinic Acid) typically used to treat what disease? Why?
CVD
Cholesterol lowering agent
Why is Nicotinic Acid unique among lipid-lowering drugs (such as statins)
Reduce LDL cholesterol (typical)
Increase HDL cholesterol Decrease Lipoprotein (a)
Benefits of niacin (nicotinic acid) with cardiovascular disease?
- lowers LDL and lipoprotein (a)
- increase HDL
- prevents progression of atherosclerotic lesions in coronary arteries
often used in combination with other drugs
Did increase HDL studies (from niacin) show decrease in heart attacks, strokes or need for angioplasty?
no
LDL lowering showed greater heart stability but no correlation to HDL levels
Niacin Flush
common side effect to niacin treatment
- abdominal pain, rash, liver toxicity
- rapidly absorbed GI tract
How to reduce niacin flush symptoms?
take with meals
avoid hot liquids + alcohol
work dose up gradually
– Extended-release niacin (Niaspan)
Large scale niacin flush problem?
Uncle Ben’s Rice
- excessive Niacin when served in food service establishments
