Chapter 4- Vitamins

Question 1

VITAMIN A

RETINOL

Answer 1

1. Antioxidant, found in liver and leafy veg
2. Constituent of visual pigments
3. Essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells)– prevents squamous metaplasia
4. Used to treat measles and AML type M#
5. Deficiency: night blindness, dry skin, vulnerable to infections
6. Excess: arthralgias, fatigue, headaches, skin changes, sore throat alopecia
7. Teratogenic! Can cause cleft palate and cardiac abnormalities

Question 2

VITAMIN B1

THIAMINE

Answer 2

1. In thiamine pyrophosphate, a cofactor for decarboxylation enzymes:
   a. Pyruvate dehydrogenase (links glycolysis to TCA cycle)
   b. a-ketoglutarate dehydrogenase (TCA cycle)
   c. Transketolase (HMP shunt)
   d. Branched-chain AA dehydrogenase
2. Deficiency: impaired glucose breakdown–> ATP depletion worsened by glucose infusion; highly aerobic tissues (brain and heart) affected first. Wernicke-Korsakoff syndrome and beriberi. Seen in malnutrition as well as alcoholism (it occurs due to malnutrition and malabsorption)
   a. W-K: confusion, opthalmoplegia, ataxia, confabulation, personality change, memory loss. Damage to medial dorsal nucleus of thalamus, mammillary bodies.
   b. Dry beriberi: polyneuritis, symmetrical muscle wasting.
   c. Wet beriberi: high-output cardiac failure (dilated cardiomyopathy), edema

Question 3

VITAMIN B2

RIBOFLAVIN

Answer 3

1. Cofactor in oxidation (loses e-) and reduction (gains e-) e.g. FAD, FMN, FADH2.
2. Deficiency: cheilosis (inflammation of lips, scaling, fissures at corners of mouth), corneal vascularization. Also, stomatitis, glossitis, dermatitis.

Question 4

VITAMIN B3

NIACIN

Answer 4

1. Constituent of NAD+, NADP+ (used in redox reactions). Derived from tryptophan. Synthesis requires Vitamin B6 and B2.
2. Deficiency: glossitis
3. Severe deficiency causes pellagra= dermatitis, diarrhea, dementia.
4. Pellagra can be caused by Hartnup disease (reduced tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism) and INH (reduced B6).
5. Excess: Facial flushing (due to pharmacologic doses for treatment of hyperlipidemia)

Question 5

VITAMIN B5

PANTOTHENATE

Answer 5

1. Essential component of CoA (a cofactor for acyl transfers) and fatty acid synthesis
2. Deficiency: dermatitis, enteritis, alopecia, adrenal insufficiency

Question 6

VITAMIN B6

PYRIDOXINE

Answer 6

1. Converted to pyridoxal phosphate, a cofactor used in transamination (e.g. ALT and AST), decarboxylation reactions, glycogen phosphorylase.
2. Synthesis of cystathionine, heme, niacin, histamine, and NT including serotonin, epi, NE, and GABA
3. Deficiency: Convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by INH and oral contraceptives), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess. Get cheilosis, glossitis, dermatitis too.

Question 7

VITAMIN B7

BIOTIN

Answer 7

1. Cofactor for carboxylation enzymes (which add a 1-carbon group)
   a. Pyruvate carboxylase: pyruvate (3C)–> oxaloacetate (4C)
   b. Acetyl-CoA carboxylase: acetyl-CoA (2C) –> malonyl-CoA (3C)
   c. Propionyl-CoA carboxylase: propionyl-CoA (3C)–> methylmalonyl CoA (4C)
2. Deficiency is relatively rare. Caused by antibiotic use or excessive ingestion of raw eggs (avidin)
3. Deficiency: dermatitis, alopecia, enteritis

Question 8

VITAMIN B9

FOLIC ACID

Answer 8

1. Converted by thetrhadydrofolate (THF), a coenzyme for 1-carbon transfer/methylation reactions.
2. Important for synthesis of nitrogenous bases in DNA and RNA.
3. Found in leafy green vegetables, small reserve pool stored primarily in the liver.
4. Deficiency: macrocytic, megaloblastic anemia; no neurological symptoms (vs B12).
5. Most common vitamin deficiency in the US, seen in alcoholism and pregnancy.
6. Deficiency can be caused by several drugs (phenytoin, sulfonamides, MTX)

Question 9

VITAMIN B12

COBALAMIN

Answer 9

1. Cofactor for homocysteine methyltransferase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase. Increases methylmalonic acid.
2. Found in animal products (strict veg can be deficient). Synthesized only by microogranisms.
3. Macrocytic, megaloblastic anemia, hypersegmented PMNs, neurologic symptoms (paresthesias, subacute combined degeneration) due to abnormal myelin. Prolonged deficiency leads to irreversible NS damage (posterior and lateral spinal cord damage)
4. We have a very large reserve pool (several years) stored in the liver. So deficiency is usually caused by malabsorption (sprue, enteritis, diphyllobothrium latum), lack of IF (pernicious anemia, gastric bypass surgery), or absence of terminal ileum (Crohn’s disease).

Question 10

VITAMIN C

ASCORBIC ACID

Answer 10

1. Antioxidant, found in fruits and veg
2. Also facilitates iron absorption by keeping iron in Fe2+ reduced state
3. Necessary for hydroxylation of proline and lysine in collagen synthesis
4. Necessary for dopamine B-hydroxylase, which converts dopamine to NE
5. Deficiency: scurvy (swollen gums, bruising, hemarthrosis, anemia, poor wound healing due to collagen synthesis defect) and weakened immune response.
6. Excess: nausea, vomiting, diarrhea, fatigue, sleep problems. Can also increase risk of iron toxicity in predisposed individuals (transfusions, hemochromatosis)

Question 11

VITAMIN D

Answer 11

1. D2= ergocalciferol- ingested from plants
   D3=cholecalciferol- consumed in milk, formed in sun-exposed skin
   25-OH D3= storage form
   1,25 OH2 D3= calcitriol-active form
2. Increases intestinal absorption of calcium and phosphate, increases bone mineralization
3. Deficiency: rickets in kids (bone pain and deformity), osteomalacia in adults (bone pain and muscle weakness), hypocalcemic tetany
4. Breast milk doesn’t have much Vitamin D (supplement in dark-skinned patients)
5. Excess: hypercalcemia, hypercalciuria, loss of appetite, stupor.
   *Seen in sarcoidosis (increased activatino of Vit D by epithelioid macrophages)

Question 12

VITAMIN E

Answer 12

1. Antioxidant-protects erythrocytes and membranes from free radical damage
2. Deficiency: Increases fragility of RBCs (hemolytic anemia), muscle weakness, posterior column and spinocerebellar tract demyelination

E for erythrocytes

Question 13

VITAMIN K

Answer 13

1. Catalyzes gamma-carboxylation of glutamic acid residues on various proteins concerned with blood clotting.
2. Synthesized by intestinal flora
3. Necessary for the synthesis of clotting factors II, VII, IX, X, proteins C and S.
4. Deficiency: neonatal hemorrhage with increased PT and aPTT but normal bleeding time (neonates have sterile intestines and are unable to synthesize vitamin K. It’s also not in breast milk). Give neonates vitamin K injection at birth to prevent hemorrhage!
5. Deficiency can also occur after prolonged use of broad-spectrum antibiotics

Question 14

ZINC

Answer 14

1. Essential for the activity of 100+ enzymes.
2. Important in formation of zinc fingers (TF motif)
3. Deficiency: delayed wound healing, hypogonadism, reduced adult hair, dysgeusia, anosmia
4. May predispose to alcohol cirrhosis.