NTR 503/403 – Metabolism II Spring 2024 Wasserbauer

Name:____Aaricka Rayburn______________________________________
Unit 1 Homework – Ch 9, Energy Vitamins: thiamin, riboflavin, niacin, pantothenic acid, biotin
Instructions: Use the lectures, notes, and textbook to answer the following questions. Please
write in your own words and do not copy directly from the powerpoints so that I can gauge
your understanding of the material. This is not a comprehensive guide for the exam however I
try to include the major topics. Homework will be graded on completeness and level of detail.
(1 point per question, 10 points total)

1. You evaluate a patient who complains of low energy and fatigue, and determine that they
have a thiamin deficiency. What are at least 3 enzymatic reactions affected by lack of
thiamin and how does this affect macronutrient metabolism?

Thiamin is essential for energy production and metabolism, therefore its effects on the
body can be critical if not addressed. Four enzymatic reactions affected by the lack of
thiamin are the pyruvate dehydrogenase complex, the α-ketoglutarate dehydrogenase
complex, branched-chain α- keto acid dehydrogenase complex, and the pentose
phosphate pathway . The pyruvate dehydrogenase complex starts at the end of the
glycolysis pathway, which is the breaking down of glucose. Thiamin is used in converting
pyruvate into acetyl-CoA, where acetyl-CoA is then used in the TCA cycle, which
ultimately ends with the ETC where ATP is produced. The α-ketoglutarate
dehydrogenase complex is part of the TCA cycle and helps convert α-ketoglutarate into
succinyl-CoA, which then continues to the ETC. The α- keto acid dehydrogenase complex
is important in the breakdown of amino acids (the building blocks of proteins)
isoleucine, leucine, and valine into succinyl-CoA. Finally, the pentose phosphate
pathway utilizes the enzyme transketolase with thiamin loosely attached to help in
DNA/RNA production and fatty acid synthesis. All macronutrients (protein, fat, and
carbohydrates) are affected by the lack of thiamin because all are part of glycolysis
pathway in some form. Therefore, incomplete breakdown of pyruvate into acetyl-CoA
and the disruption of the TCA cycle results in a decrease in ATP production and the
accumulation of pyruvate, lactate, and α-ketoglutarate.

2. a) Explain the process by which thiamin is digested and absorbed (site of GI tract, form that
is absorbed, any transporters?)

Thiamin can exist as a free form in plant foods and as phosphorylated active forms in
animal foods, 95% TDP and 5%TMP. Thiamin must become a free form before it is
absorbed by duodenum, jejunum, or the large intestine. Therefore, the active forms are
digested by intestinal phosphatases where the phosphates are removed before the
absorption in the intestines. Thiamin absorption can occur via diffusion or carrier-

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mediated active transport, all depending on the concentration gradient of thiamin. For
instance, if there is a high concentration of thiamin then passive diffusion is utilized, if
there is a low concentration of thiamin then transporters are used. These carriers are
ThTr1 and ThTr2.

b) Which dietary factors affect the integrity/stability of thiamin?

There are dietary factors that affect the integrity/stability of thiamin. Firstly, magnesium
is required for thiamin absorption. Additionally, thiamin in foods can be destroyed by
heat and alkaline environments. However, other factors are antithiamin meaning it
prevents thiamin absorption. Alcohol inhibits thiamin absorption due to its ability to
prevent the expression of the carriers of ThTr1 and ThTr2. Thiaminases found in raw fish
and polyhydroxyphenols found in coffee, tea, betel nuts, and some fruits and vegetables
also obstruct thiamin absorption. An important factor that may prevent thiamin
destruction is vitamin C.

3. a) Which coenzyme forms does riboflavin take in cells and how do they allow redox
reactions to occur?

There are two coenzyme forms that riboflavin takes in cells, FAD and FMN. A simplified
definition of a redox reaction is the movement of electrons and hydrogens in a molecule
via oxidation and reduction. Oxidation is the loss of electrons and reduction is the gain
of electrons. FAD and FMN are great oxidizing agents because of their ability to accept a
pair of hydrogen ions. Specifically, riboflavin contains an isoalloxazine ring that can be
oxidized forming FMN or FAD or the isoalloxazine ring can be reduced forming FMNH 2
or FADH2.

b) If you diagnosed a patient with a riboflavin deficiency, what are at least 3 enzymatic
reactions that would be impaired?

Three enzymatic reactions that would be impaired are the oxidative decarboxylation of
pyruvate, succinate dehydrogenase, and fatty acid beta-oxidation. The oxidative
decarboxylation of pyruvate is at the end of the glycolysis pathway and before the TCA
cycle and helps in the conversion of pyruvate to acetyl-CoA. The succinate
dehydrogenase enzyme is part of the TCA cycle and converts succinate to fumarate.
Finally, the beta-oxidation of fatty acids, where FAD is used to remove two hydrogen
from a fatty acid which then enters the ETC.

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4. a) How is riboflavin digested and what are the methods of absorption (site of GI tract, form
that is absorbed, any transporters)?

Riboflavin in foods is bound to proteins, forming FMN and FAD, and must be freed
before absorption. Hydrochloric acid in the stomach and proteases in the stomach,
pancreas, and small intestine can break the bonds. To convert FMN and FAD to free
riboflavin FAD becomes FMN by the enzymatic reaction with FAD pyrophosphatase, and
FMN becomes riboflavin by the enzymatic reaction with FMN phosphatase. The
duodenum, jejunum, and the colon all can absorb riboflavin. If there is a high
concentration of riboflavin it can diffuse across the membranes, but if there is a low
concentration there are three transporters that help with absorption, RFVT1, RFVT2,
and RFVT3.

b) If your patient is trying to increase riboflavin absorption, what are two inhibitors you
recommend they avoid?

To increase absorption of riboflavin I would recommend not drinking alcohol and avoid
the consumption of foods with divalent metals (2+ charge) such as copper, zinc, iron,
and manganese which can form chelates (chelation is the bonding of ion molecules to
metals).

5. Discuss the role of the amino acid tryptophan for adequate niacin status and other B
vitamins needed for this process.

Besides dietary niacin sources, niacin as NAD can be made in the body by the amino acid
tryptophan. The synthetization of NAD by tryptophan is performed in the liver via a
biosynthetic pathway, requiring iron, riboflavin, and PLP. It is estimated that 60mg of
tryptophan can produce 1 mg of niacin, supplying 50% of niacin intake in the U.S. The
determination of how tryptophan can affect the absorption of niacin can be seen in
individuals with Hartnup disease because the transporter for tryptophan is defective.
Additionally, the inadequate intakes of FAD (riboflavin), PLP (vitamin B6), and iron can
impair niacin synthesis.

6. a) What are the signs and symptoms of a niacin deficiency and what condition is this called?

A deficiency in niacin leads to a condition called pellagra. There are four Ds that are
used as a mnemonic device for remembering the signs, dermatitis, dementia, diarrhea,
and death. The dermatitis starts appearing like a sunburn but eventually becomes
hyperpigmented, rough, and cracked. Diarrhea occurs due to the inflammation of the
mucosa, with other gastrointestinal manifestations including glossitis, cheilosis, angular

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stomatitis, nausea, and vomiting. Dementia occurs later in the disease can include
headache, apathy, fatigue, loss of memory, peripheral neuritis, paralysis of extremities,
depression, confusion, disorientation, delusions, hallucinations, and delirium. Finally, if
pellagra is untreated it leads to death.

b) Your patient reports supplementing with 50 mg/day of nicotinic acid. What side effects
could result from this?

According to the Food and Nutrition Board the upper-level intake for adults for niacin (in
both forms, nicotinic acid and nicotinamide) from fortified foods and supplements is
35mg/day. Therefore, if a patient is supplementing with 50mg/day of nicotinic acid it can
lead to vasodilatory effects such as flushing. Also, burning, itching, tingling, headaches, GI
issues like heartburn, nausea, and vomiting, liver injury, hyperuricemia (too much uric acid
in blood), and possible gout and glucose intolerance may occur.

7. a) Pantothenic acid can be found in its free form but often exists as coenzyme A. Why is
coenzyme A essential for numerous metabolic reactions?
Coenzyme A is involved in nutrient metabolism and energy production. One of the
important parts of the structure of coenzyme A is the active site (-SH) which can form a
thio-ester bond allowing acyl groups such as acetyl and succinyl to attach. The thio-ester
bond is a high energy bond that converts food into usable energy.

b) What are 3 pathways that cannot function without pantothenic acid in the diet?

CoA and its derivatives function in hundreds of metabolic reactions, including the
metabolism of carbohydrates, lipids, and proteins. One pathway is the oxidative
decarboxylation of pyruvate where CoA helps convert pyruvate to acetyl-CoA by
attaching itself to the acetyl group. Also, pantothenic acid participates in the TCA cycle
by being involved in the oxidative decarboxylation of α-ketoglutarate to succinyl-CoA
(attaching itself to succinyl). Finally, pantothenic acid acts in fatty acid synthesis by
converting itself, with the help of CO2, biotin, ATP, and acetyl-CoA carboxylase to
malonyl-CoA which is a key metabolite in fatty acid synthesis.

8. a) What happens when biotin binds to apocarboxylases and what does this do for metabolic
reactions?
An apocarboxylases are carboxylases without being bound to biotin. The attachment of
the apocarboxylases to biotin called biotinylation is done by holocarboxylase synthetase
which turns the apocarboxylases to holocarboxylases. The importance of binding biotin
to the carboxylases is to carry CO2 for carboxylation reactions. Additionally, the breaking
down of the biotin carboxylases yields biocytin. Biocytin is an amide formed from biotin

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and the amino acid L-lysine. The enzyme biotinidase splits biocytin which makes biotin
available to be used by other enzymes or excreted.

b) Name 2 types of carboxylases and their substrates and end products.

Pyruvate carboxylase is a biotin dependent mitochondrial enzyme that converts

pyruvate to oxaloacetate. Oxaloacetate is a substrate for gluconeogenesis, the pathway
to form a new glucose molecule. Additionally, oxaloacetate is also used to replenish the
oxaloacetate in the TCA cycle, helping to create more ATP.

Β-methylcrotonyl CoA carboxylase, a mitochondrial enzyme, converts Β-methylcrotonyl-

CoA to Β-methylglutaconyl-CoA in the degradation of the amino acid leucine. The
catabolism of leucine produces acetoacetate and acetyl-CoA. Acetoacetate is used in the
ketogenesis pathway to form ketone bodies. The acetyl-CoA main function is the TCA
cycle that helps in producing more ATP.

9. Name the nutrient-medication interactions for the energy vitamins:

a. Thiamin Furosemide (diuretic) and Theophylline (bronchodilator)
b. Riboflavin- Tricyclic antidepressant meds and Tetracycline (antibiotic)
c. Niacin- Isoniazid (tuberculosis drug) and Mercaptopurine (cancer/autoimmune
treatment
d. Pantothenic acid- tetracycline (antibiotic)
e. Biotin- Anticonvulsant drug therapies (phenobarbital, phenytoin,
carbamazepine)

10. Name at least 3 populations at risk of deficiency for the following energy vitamins:
a. Thiamin- chronic alcoholics, older adults, patients with diabetes
b. Riboflavin- chronic alcoholics, patients with thyroid disease, diabetics
c. Niacin- chronic alcoholics, older adults, patients with Hartnup disease
d. Pantothenic acid- chronic alcoholics, diabetics, patients with inflammatory bowel
disease
e. Biotin-patients with partial gastrectomy, chronic alcoholics, patients with GI
disorders (IBD)