Vitamins and Minerals

Question 1

Vitamin A

Answer 1

Retinoids

• 11-cis retinal required for vision
• Retinoic Acid required for mucus secreting cells (specialized epithelium), and growth
• Retinol required for reproduction

Transported in blood via retinol binding protein (Alpha 1 plasma protein)

Question 2

Mechanism of action of Retinol in vision

Answer 2

1. Retinol transported in to retinal pigment cell
2. Retinol converted to 11-cis retinal and enters photoreceptor (rod) cell
3. 11-cis retinal combines with Opsin to form Rhodopsin
4. Absorption of photon catalyzes isomerization of 11-cis retinal to all-trans-retinol leading to an electrical signal

Question 3

Mechanism of action of Retinoic acid in epithelial cells

Answer 3

Retinol enters epithelial cells and is oxidized to Retinoic Acid

Retinoic Acid moved from cytosol to nucleus and binds with receptor

Retinoic acid-receptor complex binds to chromatin activating the transcription of specific genes (keratin)

Question 4

Vitamin A Deficiency

Answer 4

Due to deficiency in diet or malabsorption

Causes:

• Night blindness
• Xeropthalmia- dryness of conjunctiva and cornea
• Bitot’s Spots - build up of keratin in the conjuntiva
• Keratomalacia - corneal erosion and ulceration
• Increased pulmonary infections- epithelium not maintained
• Immune Deficiency

Question 5

Vitamin A Toxicity

Answer 5

• Hypervitaminosis A –raised intracranial pressure –headaches –may mimic brain tumors
• Dry and pruritic skin
• Enlarged liver
• Pregnancy –spontaneous abortions and congenital malformations in the fetus.

Question 6

7-dehydrocholesterol

Answer 6

Intermediate in cholesterol synthesis

Forms Cholecalciferol (D3) in the skin

Question 7

1,25-dihydroxycholecalciferol

Answer 7

Active form of Vitamin D. formed by two rounds of hydroxylation of vitamin D precursors

Round 1 in Liver
Round 2 in Kidney

Has a similar method of action as that of Vitamin A

Question 8

Vitamin D Deficiency

Answer 8

Due to malabsorption, inadequate sunlight, chronic liver or renal disease

Causes:

• Rickets in children
• Overgrowth of costochondral junction - rachitic rosary
• Pigeon chest
• Osteomalacia in adults

Question 9

Alpha tocopherol

Answer 9

Most active form of Vitamin E

Most important role is as an antioxidant

Deficiency:

• Hemolytic Anemia- abnormal cell membranes
• Reduced deep tendon reflexs and gait problems due to axonal degradation

Question 10

Vitamin K

Answer 10

Cofactor in gamma-carboxylase in formation of clotting factors II, VII, IX, X as well as protein C and S

In humans it is synthesized by bacterial flora or obtained in the diet.

–Phylloquinone(plants) –dietary source
–Menaquinone(bacteria) -intestine

Question 11

Vitamin K Deficiency

Answer 11

Neonates:
Hemorrhagic Disease - Bleeding at various sites of the body

Adults:
Hematuria
Melena - black tarry stools
Eccymoses - bruises
Bleeding from the gums

Question 12

Vitamin C

Answer 12

Ascorbic Acid

Required for maintenance of normal connective tissue (collagen synthesis (Pro hydroxylation)) and wound healing

Required for the absorption of Iron - reduces Iron in the stomach

Antioxidant

Deficiency causes scurvy

Question 13

Thiamine

Answer 13

Vitamin B1

Required Cofactor for:

• pyruvate dehydrogenase (pyruvate to Acetyl CoA)
• Alpha-ketoglutarate dehydrogenase (TCA Cycle)
• Branched chain Alpha-ketoacid dehydrogenase (metabolism of BCAA)
• Acts as a coenzyme for transketolase in the pentose phosphate shunt

Question 14

TTP Deficieny

Answer 14

Dry BeriBeri: polyneuropathy that can lead to paralysis

Wet BeriBeri: Cardiac failure

Wernicke-Korsakoff Syndrome:
Associated with chronic alcoholism
•Ophthalmoplegiaand nystagmus(to and fro movement of eyeballs)
•Ataxia, confusion, disorientation and loss of memory
•Confabulation

(Diagnosis –increase in erythrocyte transketolaseactivity on addition of TPP)

Question 15

Riboflavin

Answer 15

VItamin B2

Coenzyme forms: FAD/FADH2 and FMN

Participates in oxidation –reduction reactions of TCA cycle, beta oxidation (Succinate dehydrogenase, PDH, Acyl CoA DH…..)

Question 16

FAD Deficiency

Answer 16

Nutritional deficiency

Signs and symptoms
•Cheilosis–areas of pallor, cracks and fissures at the angles of the mouth
•Glossitis–inflammation and atrophy of the tongue
•Facial dermatitis

Question 17

Niacin

Answer 17

Vitamin B3

Act as coenzymes in oxidation-reduction reactions
–NAD+ –Dehydrogenases
–NADP+ –Reactions in the HMP shunt and fatty acid synthesis

Therapeutic uses:
–Niacin inhibits lipolysis in the adipose tissue and greatly reduces production of free fatty acids –treatment of type IIb hyperlipoproteinemia

Tryptophan can be used to synthesize NAD+ and NADP+

Question 18

Vitamin B3 Deficiency

Answer 18

Pallagra

Characterized by dermatitis, dementia, Diarrhea, and can lead to death

Patients with Hartnup’sdisease can have pellagra-like symptoms*** -Need supplementation of dietary niacin

•Patients with carcinoid syndrome may also have pellagra

Question 19

Biotin

Answer 19

Vitamin B7

Prosthetic group for most carboxylation reactions

• Pyruvate carboxylase
• Acetyl-CoA carboxylase (FA Synthesis)
• Propionyl-CoA carboxylase (Odd chain FA oxidation)

Question 20

Pyridoxine

Answer 20

Vitamin B6

Precursor for pyridoxyl phosphate (PLP) which is a coenzyme for:
–Transamination (amino acid metabolism)
–Amino acid decarboxylation (synthesis of neurotransmitters)
–Condensation (ALA synthase in heme synthesis)
–Conversion of homocysteine to cysteine

Question 21

Vitamin B6 Deficiency

Answer 21

Caused by Izoniazide administration for TB

Signs and symptoms:
•Microcytic anemia (ALA synthase in Heme)
•Peripheral neuropathy (reduced neurotransmitters)
•Increased risk of cardiovascular disease (high levels of plasma homocysteine)
•Seizures may occur

Question 22

Cobalamin

Answer 22

Vitamin B12

Intrinsic Factor required for absorption

• Synthesis of Met from homocysteine.
• Converts methyl tetrahydrofolate to tetrahydrofolate (THF) required for DNA synthesis
• Conversion of FA, BCAA and Met to Succynyl CoA (a methylmalonyl CoA mutase cofactor)

Question 23

Vitamin B12 Deficiency

Answer 23

Macrocytic anemia - trapped THF in methyl form (

Neurological manifestations - accumulation of methylmalonate in the body. (Methylmalonyl aciduria)

Pernicious anemia - Lack of Intrinsic Factor for Vitamin B12 absorption from animal foods

Question 24

Folic Acid

Answer 24

Vitamin B9

Active form is Tetrahydrofolate (THF) produced by dihydrofolate reductase (requires 2 NADPH)

• Key role in one carbon metabolism
  THF receives one-carbon fragments from donors and transfers them to intermediates in purine and pyrimidine synthesis
• Synthesis of Met to homocystine
• Degradation of Histidine (FlGlu to glutamate)
• Conversion of Serine to Glycine

Question 25

Vitamin B9 Deficiency

Answer 25

Folate dediciency due to lack of dietary intake (fruits and veg), impaired absorption &/or reabsorption, Methotrexate administration, trapping due to Vit B12 deficiency - Megaloblastic anemia - inability for cells to synthesize DNA due to lack of purines and pyrimidines - Homocystinuria High FlGlu in urine used as a test for folate deficiency (Never treat with Folic acid alone!! always pair with Vit B12 till definite cause is established) Most common vitamin deficiency

Question 26

Copper Reactions

Answer 26

Cytochrome C - Part of complex IV of the Electron transport chain Superoxide Dismutase Lysyl and prolyl Oxidase - Synthesis of Collagen Tyrosinase - Sythesis of Melanin Dopamine Beta-hydroxylase - Neurotransmitter synthesis Ceruloplasm formation in the liver

Question 27

Copper Deficiency

Answer 27

Microcytic Anemia - Ceruloplasm needed for Iron metabolism in Heme formation Vascular tissue degradation/aneurysm formation due to decreased lysyl and Pro oxidase activity Menke’s syndrome

Question 28

Menke's Syndrome

Answer 28

Inherited defect in absorption of copper from the GI tract. Hair is twisty, grayish and “kinky” •Copper deficiency can lead to aneurysms and cerebral dysfunction X-linked

Question 29

Wilson's Disease

Answer 29

Accumulation of toxic levels of copper in vital organs including liver, brain and eye Defect is found in the copper transporting ATPase in the liver needed to attach copper to ceruloplasmin and also to excrete copper into the bile

Question 30

Iron

Answer 30

Required for Heme synthesis and in redox reations Heme from meat better absorbed. Veg need to be transferred to Ferric Iron (Fe+++) by low pH and vit C for absorption Ceruloplasmin (ferroxidase) participates in the release of ferrous iron (Fe++) from intestinal cells and forms ferric iron which is needed for transport in the blood

Question 31

Iron Deficency

Answer 31

Hypochromic microcytc anemia Chronic bleeding Fatigue brittle nails Pica (appetite for dirt)

Question 32

Hereditary Hemochromatosis

Answer 32

Excessive absorption of Iron Autosomal recessive Excess iron damages tissues by: •Lipid peroxidationthrough free radicals •DNA damage Clinical Features: •More common in males; presenting age 40 •Liver damage –cirrhosis; hepatocellular carcinoma •Diabetes –destruction of pancreas •Cardiac dysfunction •Acute synovitis •Brownish skin pigmentation (Bronze color of skin)

Question 33

Nutritional Anemias

Answer 33

``` MICROCYTIC - reduced synthesis of heme Seen in Deficiency of: Iron Copper Vit B6 (PLP) - ALA synthase cofactor ``` MACROCYTIC - reduced cell division Seen in Deficiency of Vitamin B12 and Folic Acid

Question 34

Zinc

Answer 34

wound healling

Question 35

Cystein

Answer 35

An AA formed from homocystein. requires Vit B6. - Forms Taurine via cystein deoxygenase - A precursor of PAPS for sulfination reactions.

Question 36

Methotrexate

Answer 36

Competitively inhibits Dihydrofolate Reductase in THF synthesis from folate Used to treat psoriasis, arthritis and neoplastic diseases. Sulfonamides do the same in microorganisms. (block dihydropterate synthetase)