They were discovered as "accessory growth factors" when dietary components other than carbs, protein, fats, minerals and water were necessary to maintain optimal growth and health.
What are some examples of how vitamins were used in the past?
1. Egyptians ate liver to cure night blindness (Vitamin A deficiency causes night blindness). 2. Sailors succumbed to scurvy until Lind (1749) recommended fruits and vegies---British sailors called "Limeys".
How are Vitamins named?
They are named alphabetically (roughly) and renamed "vitamins" when most were found to NOT be amines.
Quantative estimates of nutrient intakes used for planning and assessing diets for apparently healthy people.
What reference values are included?
EAR, RDA, AI, UL
Estimated Agerage Requirement: Average daily nutrient intake ADNI estimated to meet the requirement of half the healthy individuals in a particular life stage and gender group (mean +/- SD)
Adequate Intake: ADNI based on observed/determined estimates of nutrient intake by a group of apparently healthy people that are assumed to be adequate (cannot be based on RDA)
Recommended Dietary Allowances: ADNI sufficient to meet the nutrient requirement of nearly all (~97%) healthy individuals ina particular life stage and gender group (based on EAR)
Tolerable Upper Intake: Highest ADNI that is likely to pose no risk of adverse health affects to almost all individuals in the general population (toxicity).
What should we focus on in the class?
1. Sources/Bioavailability 2. Absorption, transport, and storage. 3. Function: Metabolism (what it does) and Biochemistry (how it does it). 4. Assesement. 5. Deficiency/Toxicity/Interactions
Pork and liver products, Whole grains, dried legumes, most nuts, yeast.
What is a poor source of Thiamin?
Vegetables and milk (Cows milk has more thiamin than human milk, leads infants to have thiamin deficiency if they are only fed human milk)
Thiamin bioavailability: Milling of grains
Whole wheat flour has 0.6 mg/100g. White flour has a lot less thiamin 0.1mg/100g. So, white flour is enriched to replace the loss in the USA.
Thiamin bioavailability: Cooking Losses
Thiamin is water soluable so it is extracted into cooking water . Alkaline conditions will cause it to break down.
Thiamin bioavailability: Thiaminases
Enzymes present in some uncooked foods (raw fish, beans, rice polishings, and mustard seed) split the bond between the thiamin rings and render the vitamin inactive. All of these enzymes are destroyed by heating.
Thiamin bioavailability: Thiamin antagonists
Tea (especially green tea) and coffee contain a thiamin antagonist (polyhydroxyphenols) that interferes with the utilization of thiamin.
What is the only form in which Thiamin is absorbed?
as free thiamin
Absorption of Thiamin
Absorption is high but depends on luminal concentration: 1. at low (<1.25 uM) conc, abs is active and dependent on the counter-transport of hydrogen ions. Active transport requires thiamin transporters ThTr1 and ThTr2. 2. At high conc, absorption is passive.
Transport of Thiamin
Thiamin transport across the basolateral membrane is ATP and Na dependent. Ethanol interferes with this process. ThTr2 is required for transport across the basolateral membrane.
The active transport of thiamin requires...
ThTr1 and ThTr2
Ethanol interferes with what process?
Thiamin transport across the basolateral membrane.
Within cells, most free thiamin is...
phosphorylated to TDP
Function of Thiamin
Critical role in oxidative decarboxylation. Magnesium is required to achieve binding of the thiamin cofactor to its apoenzymes.
it removes a carbon as CO2. It converts pyruvate to acetyl CoA and is inactive when there is a thiamin deficiency.
What does Dihydrolipoyl transacetylase do?
It transfers an acetyl group to lipoic acid. The acetyl group is then tranferred from acetyl lipoic acid to CoA with the formation of acetyl CoA and dihydrolipoamide.
What does Dihydrolipoyl dehydrogenase do?
It reoxidizes (takes off H) to reactivate the system. FADH2 is oxidized by NAD+.
Branched-chain amino acid metabolism
1. functions similar to pyruvate dehydrogenase. 2. Decarboxylation of a-keto acids requires thiamin as a cofactor for branched chain a-keto dehydrogenase. 3. ketoacids arise from transamination of valine, isoleucine, and leucine. 4. Faliure results in a ccumulation of branched-chain and un-oxidized keto-acids in the blood (maple sugar urine disease.
what are the three branched chain amino acids?
valine, isoleucine, and leucine
What is Maple Sugar Urine Disease?
It is when a-keto acid dehydrogenase fails (possibly because of a thiamin deficiency). Branched-chain and unoxidized ketoacids (arising from leucine, isoleucine, and valine) are backed up into the urine. The urine comes our dark brown and smells bad. This is a 1 in 180,000 incidence and it may result in death.
an important enzyme in the pentose shunt; links glycolysis with the pentose shunt and generates important intermediates not produced elsewhere.
Pentose Shunt (hexose monophosphate shunt)
1. interconversion of sugars of varying chain lengths; necessary for fatty acid biosynthesis (NADPH; oxidative state) and the production of nucleic acids (pentose phosphates; non-oxidative stage) 2. very imp in synthetic tissues like mammary gland, adipose, liver, adrenals because NADPH is needed for synth rxns. A Catabolic rxn will use NAD+ and a synth rxn will use NADPH.
In the liver, 60% of CHO may be metabolized by what pathway?
Which requires the cofactor thiamin diphosphate TDP ?
Transketolase, not transaldolase
What are other energetic roles of thiamin?
1. TDP is required for the a-oxidation and cleavage of 3-methyl fatty acids enabling them to enter the B-oxidation pathway. 2. Thaimin triphosphate is essential for the regulation and movement of Cl- ions and the regulation of Na+ channels across neural membranes.
It affects nervous tissue independent of its role as a coenzyme, polyneuritisis a characteristic of thaimin deficiency.
This is when the person does not make thaimin triphosphate and they have neurological problems similar to thiamin deficiency.
Metabolism and Excretion
1. Thaimin can be excreted intact or it can be metabolized for urinary excretion (cleavage of pyrimidine and thiazole rings). 2. Rate of thaimin degredation does not vary greatly with variation in thiamin intake or stores (20-30 metabolites of thaimin can be generated).
RDA of thiamin
No UL (no adverse affects associated with high intakes from food or supplements), 0.2 - 0.3 mg/d for infants, 1-1.2 for adults, 1.4 for preggers
What does Beriberi mean in singhalese?
I cant I cant
What is the deficiency of thiamin called?
1. Very common where polished grains comprise 80% of diet. 2. Digestive problems: anorexia, nausea, vomiting, constipation. 3. Cardiac symptoms: heart enlargement bradycardia (early beriberi), tachycardia (late beriberi), cynanosis (blue skin), coldness of extremities.
Beriberi neurological symptoms
Alterations in reflexes, motor disturbances, inability to raise hands/toes, paresthesia (tingling), numbness of feet and heaviness of legs, muscles are tender and painful. Impossible to explain all of thiamins manefestations.
a genetic determinant that says what type of a disease you will have
1. Edemic 2. extensive cardiac problems. 3. edema starts at feet and progresses upward. 4. Peripheral vasodialation, Progressive vasodialation, the resulting fluid overload leads to edema of the dependent extremities.
Wet Beriberi: peripheral vasodialation
high cardiac output, salt and water retention mediated through the renin-angiotensin-aldosterone system in the kidneys.
wet beriberi: progressive vasodialation
salt retention; fluid is also absorbed into the circulatory system
1. extensive neurological problems; does not generally include cardiac problems. 2. chiefly occurs in older adults to low intake 3. rat arches back because everything hurts, bird loses ability to move head, and cocks it back.
1. very rapid onset, may die of heart faliure within a few hours. 2. gastrointestinal malfunction. 3. in acute stage: cyanosis, dyspnea (trouble breathing), aphonia (inability to speak), neck retraction (like chicken), edema, convulsions.
Wernicke's Encephalopathy: symptoms
Ophthalmoplegia (paralysis of eye muscles), Nystagmus (constant, involuntary eyeball movements), Ataxia of gait (imparied muscles coordination), mental disturbances (apathy, confusion, delirium), severe stages develop to coma, multiple brain regions are affected.
Wernicke's Encephalopathy results from...
1. decreased thiamin intake due to decreased food consumption. 2. decreased thaimin absorption (ThTr2 is impaired) (acute: 12% ETOH and red wine, chronic: 12% ETOH for 21d). 3. increased requirement due to liver damage; liver damage impairs TDP formation.
Korsakoff psychosis is generally considered to occur...
following neurological deterioration in patients with WE. it is the loss of retentive memory.
Wernicke's Encephalopathy and stats and consequences
1. in US and other western countries, thiamin deficiency associated with alcoholism and elders. 2. most alcoholics admitted to a hospital in a coma are suffering from WE. 3. Fatality without thiamin is about 90% after treatment with thaimin and Mg+ the overall condition improves. Never give them glucose because they wont be able to metabolize it; without thaimin, pyruvate dehydrogenase doesnt work, pyruvate is backed up, and the person will get lactic acidosis.
If alcoholic does not come out of coma promptly...
within the first 48 to 72 hours, Korsakoff's psychosis usually develops (> 50% of WE cases)
How do you assess thiamin status?
1. Do a transketolase assay 2. urinary thiamin level (less than 27 ug/g creatinine suggests deficiency)
This enzyme is used to assess thiamin status from erythrocytes. The RBC's are lysed; the enzyme activity in the presence and absence of excess TDP is measured. Transketolase Activity Coefficient = (activity w/TDP) / (activity w/o TDP)
During the Transketolase Assay, the lower the Transketolase Activity Coefficient the (less/more) thiamin in your body.
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