Vitamins and Minerals Flashcards
Vitamin A
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)
Mechanism of action of Retinol in vision
- Retinol transported in to retinal pigment cell
- Retinol converted to 11-cis retinal and enters photoreceptor (rod) cell
- 11-cis retinal combines with Opsin to form Rhodopsin
- Absorption of photon catalyzes isomerization of 11-cis retinal to all-trans-retinol leading to an electrical signal
Mechanism of action of Retinoic acid in epithelial cells
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)
Vitamin A Deficiency
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
Vitamin A Toxicity
- 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.
7-dehydrocholesterol
Intermediate in cholesterol synthesis
Forms Cholecalciferol (D3) in the skin
1,25-dihydroxycholecalciferol
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
Vitamin D Deficiency
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
Alpha tocopherol
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
Vitamin K
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
Vitamin K Deficiency
Neonates:
Hemorrhagic Disease - Bleeding at various sites of the body
Adults: Hematuria Melena - black tarry stools Eccymoses - bruises Bleeding from the gums
Vitamin C
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
Thiamine
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
TTP Deficieny
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)
Riboflavin
VItamin B2
Coenzyme forms: FAD/FADH2 and FMN
Participates in oxidation –reduction reactions of TCA cycle, beta oxidation (Succinate dehydrogenase, PDH, Acyl CoA DH…..)
FAD Deficiency
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
Niacin
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+
Vitamin B3 Deficiency
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
Biotin
Vitamin B7
Prosthetic group for most carboxylation reactions
- Pyruvate carboxylase
- Acetyl-CoA carboxylase (FA Synthesis)
- Propionyl-CoA carboxylase (Odd chain FA oxidation)
Pyridoxine
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
Vitamin B6 Deficiency
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
Cobalamin
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)
Vitamin B12 Deficiency
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
Folic Acid
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
Vitamin B9 Deficiency
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
Copper Reactions
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
Copper Deficiency
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
Menke’s Syndrome
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
Wilson’s Disease
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
Iron
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
Iron Deficency
Hypochromic microcytc anemia
Chronic bleeding
Fatigue
brittle nails
Pica (appetite for dirt)
Hereditary Hemochromatosis
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)
Nutritional Anemias
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
Zinc
wound healling
Cystein
An AA formed from homocystein. requires Vit B6.
- Forms Taurine via cystein deoxygenase
- A precursor of PAPS for sulfination reactions.
Methotrexate
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)
