NHM 573 - Exam 2

Biotin, Thiamin, Riboflavin, Niacin, Pantothenic Acid

What is biotin essential for?

Fatty acid synthesis, gluconeogenesis, propionyl-CoA metabolism, and gene expression.

What are major food sources of biotin?

Egg yolks, nuts/seeds, liver, whole grains, legumes, dairy products, and biotin produced by gut microbiota.

Why is there no RDA for biotin?

The evidence was insufficient to establish an EAR and RDA, so only an AI was established.

What is the AI for biotin for adults?

30 µg/day for adults 19+.

What is the biotin AI during pregnancy and lactation?

Pregnancy: 30 µg/day
Lactation: 35 µg/day

What form is dietary biotin usually found in?

Protein-bound biotin.

What happens to protein-bound biotin during digestion?

Proteases and peptidases break the protein-bound biotin into biocytin (biotin-lysine) or biotin oligopeptides.

What enzyme releases biotin from biocytin and biotin oligopeptides?

Biotinidase.

Where is biotinidase expressed?

The brush-border membrane.

What transporter absorbs biotin?

Sodium-dependent multivitamin transporter (SMVT).

Where is biotin absorption greatest?

The jejunum.

How well are biotin supplements absorbed?

Approximately 100% absorbed.

What is the main organ involved in biotin recycling?

The liver.

What type of enzymes require biotin as a coenzyme?

Carboxylase enzymes.

What enzyme uses biotin for fatty acid synthesis?

Acetyl-CoA carboxylase (ACC).

What enzyme uses biotin for gluconeogenesis?

Pyruvate carboxylase (PC).

What enzyme uses biotin for odd-chain fatty acid and certain amino acid metabolism?

Propionyl-CoA carboxylase (PCC).

Which amino acids are listed with propionyl-CoA carboxylase?

Valine, isoleucine, methionine, and threonine.

What enzyme requires biotin for leucine metabolism?

Methylcrotonyl-CoA carboxylase (MCC).

What are the four major biotin-dependent carboxylases?

ACC, PC, PCC, and MCC.

What is histone biotinylation?

Biotin is transferred to lysine residues on histones, producing a diet-related epigenetic modification involved in gene regulation.

What enzyme transfers biotin to lysines on histones?

Biotinidase.

During which phases of the cell cycle does histone biotinylation increase?

G1, S, G2, and M compared with G0.

Is histone biotinylation greater in proliferating or quiescent cells?

Proliferating cells.

What does histone biotinylation indicate?

It is part of a mechanism involved in cell-cycle regulation and gene expression.

Has biotin toxicity been reported at very high doses?

Toxicity has not been reported, even with pharmacological doses 300–600 times normal dietary intake.

What potential concern exists with very high biotin doses?

Possible long-term epigenetic consequences.

Is biotin deficiency common?

No. It is very rare in healthy populations.

How can raw egg whites cause biotin deficiency?

Raw egg whites contain avidin, which binds biotin and prevents its absorption.

How can alcoholism contribute to biotin deficiency?

It can reduce SMVT1 expression, impairing biotin absorption/uptake.

What can mutations in the SMVT gene cause?

Impaired biotin absorption and uptake.

What can mutations in the biotinidase gene cause?

Impaired biotin absorption and recycling.

What is thiamin essential for?

Energy-nutrient metabolism and the pentose phosphate pathway.

What are major food sources of thiamin?

Fortified grains/cereals, pork, legumes, fish, and seafood.

What is the adult RDA for thiamin?

Men 19–50: 1.2 mg/day
Women 19–50: 1.1 mg/day

What are the pregnancy and lactation RDAs for thiamin?

1.4 mg/day for both pregnancy and lactation.

What is the RDA for adults 51+?

Men: 1.2 mg/day
Women: 1.1 mg/day

What is the primary active coenzyme form of thiamin?

Thiamin pyrophosphate (TPP), also called thiamin diphosphate (ThDP).

In what form is dietary thiamin mainly found?

Bound to protein.

What must happen to thiamin before absorption?

Protein-bound thiamin must undergo hydrolysis.

What enzyme converts phosphorylated thiamin derivatives into free thiamin?

Intestinal alkaline phosphatase.

What transporter moves thiamin into and out of the enterocyte?

THTR1

What transporter is used for thiamin uptake only?

THTR2

How can thiamin enter/leave the intestine at high concentrations?

Through passive diffusion.

What happens to free thiamin inside the enterocyte?

It can be converted to TPP by thiamin pyrophosphokinase (TPK1).

What happens to free thiamin inside the enterocyte?

It can be converted to TPP by thiamin pyrophosphokinase (TPK1).

What enzyme can remove phosphate from thiamin?

A phosphatase enzyme.

What types of cells have high thiamin requirements?

Neurons, enterocytes/blood cells, hepatocytes/adipocytes, and heart/muscle cells.

Why are serum thiamin concentrations low?

Cellular and bone marrow uptake is rapid, so serum concentrations remain low.

What is the major active form of thiamin?

TPP/ThDP.

What major type of reaction requires thiamin?

Oxidative decarboxylation reactions.

What happens in the pyruvate dehydrogenase complex?

Pyruvate → acetyl-CoA, and ThDP is required.

What is the first enzyme in the pyruvate dehydrogenase complex?

Pyruvate decarboxylase.

What does ThDP do in pyruvate dehydrogenase?

It acts as an intermediate to transfer the hydroxyethyl group to lipoic acid, while CO₂ is removed.

What enzyme complex uses ThDP to convert α-ketoglutarate?

Alpha-ketoglutarate dehydrogenase complex.

What does α-ketoglutarate dehydrogenase produce?

NADH and succinyl-CoA.

Where does α-ketoglutarate dehydrogenase occur?

In the mitochondria.

What other processes are associated with the α-ketoglutarate dehydrogenase reaction?

Krebs cycle, porphyrin/heme synthesis, and ketone metabolism.

What enzyme complex requires ThDP for BCAA metabolism?

Branched-chain ketoacid dehydrogenase (BCKD) complex.

What are the three catalytic components of BCKD?

E1, E2, and E3.

What happens in Step 1 of BCKD?

Decarboxylation produces CO₂ and an acyl group.

What happens in Step 2 of BCKD?

The acyl group attaches to ThDP.

What happens in Step 3?

The acyl group is transferred to a lipoic acid derivative.

What happens in Step 4?

CoA is attached.

What enzyme requires ThDP in the pentose phosphate pathway?

Transketolase.

What type of reactions does transketolase catalyze?

Two reversible reactions in the nonoxidative pentose phosphate pathway.

What is the first transketolase reaction?

Xylulose-5-P + ribose-5-P → glyceraldehyde-3-P + sedoheptulose-7-P.

What is the second transketolase reaction?

Xylulose-5-P + erythrose-4-P → glyceraldehyde-3-P + fructose-6-P.

What does transketolase regulate?

It regulates carbon flux between the nonoxidative PPP and glycolysis/gluconeogenesis.

What is ribose-5-phosphate used to synthesize?

Ribose portions of NAD⁺, FAD, CoA, purine nucleotides, and pyrimidine nucleotides.

What is beriberi?

A disease caused by severe thiamin deficiency.

What is dry beriberi?

Thiamin deficiency primarily affecting the nervous system/lower limbs, including polyneuritis, burning feet, weakness, cramps, and muscle pain.

What is wet beriberi?

Thiamin deficiency associated with cardiovascular effects, including congestive heart failure, edema, pulmonary hypertension, and lactic acidosis.

Why are the nervous system and heart particularly affected by thiamin deficiency?

They have high metabolic demands.

Can severe beriberi be fatal?

Yes

What is Wernicke-Korsakoff syndrome associated with?

Severe thiamin deficiency, especially alcohol-related deficiency.

How does alcohol contribute to thiamin deficiency?

Alcohol reduces intestinal expression of thiamin transporters THTR2/3, impairing absorption.

What are symptoms of Wernicke encephalopathy?

Confusion and ataxia, with severe brain impairment/encephalopathy.

What can occur if deficiency is prolonged?

Psychosis, amnesia, learning defects, personality changes, and permanent lesions.

What non-alcohol-related conditions can increase Wernicke-Korsakoff risk?

Gastrectomy, rapidly growing hepatic tumors, drug abuse, and AIDS.

What increases thiamin requirements?

Higher carbohydrate intake and physiological stress.

Who may be susceptible to thiamin deficiency?

People using diuretics or with kidney failure.

What condition is associated with thiamin deficiency during nutritional rehabilitation?

Refeeding syndrome.

Is thiamin toxicity common?

No. Toxicity is rare.

What therapeutic doses are listed for thiamin in the PowerPoint?

10–100 mg/day.

How is thiamin status assessed using erythrocyte transketolase?

Transketolase activity is measured before and after adding TPP. The percentage increase is called the TPP effect.

What TPP effect indicates normal thiamin status?

<15%