Vitamins and Minerals

• Vitamin A: Vision, reproduction, growth, epithelial cells (immune function)

  Note: treatment for acne and psoriasis, measles therapy 
• 2 active forms of Vitamin A

  Vitamin A1 (Retinol) → liver of saltwater fish

  Vitamin A2 (3-dihydroxy retinol) → liver of freshwater fish

  8 stereoisomers → form photoactive pigments in Retina for vision
• Retinol (active)

  Complex primary alcohol containing a beta-ionone ring with an unsaturated side chain

  Carotene/ Pro Vitamin A (inactive)

  Forms: 

  Alpha and Gamma → 1 mole

  Beta → 2 moles 
• Bile acids are needed for absorption of carotene but not Vitamin A

  Rhodopsin Cycle
• Vitamin A deficiency

  • Dry eyes
  • Dry skin → fish scales
  • Anti-infective vitamin → does not destroy organisms but increase integrity of skin
  • Urolithiasis 

  Avitaminosis A → When Vit A is depleted fast 
• Hypervitaminosis A

  Caused by toxicity of vit A (>7.5 mg per day) 

  • Acute phase: single administration of 1,000,000 units or more.
  • Chronic phase: SKIN is affected (dry and pruritic); long-time ingestion of 100,00 units daily
• Vitamin A is stored in Liver
• Vitamin D: Hormone-like function

  Calcium and phosphorus metabolism (changes pH of small intestine)

  Citrate complex for bone absorption (+ bone formation)
• Active Vitamin D: Cod liver oil and other fish oil → Ergocalciferol (Vitamin D2): plants 

  Cholecalciferol (Vitamin D3): animal tissues

  Endogenous vitamin precursor: provitamins, ergosterol, 7-dehydrocholesterol (layers of skin)
• Vitamin D2 (Ergocalciferol) → from ergosterol through photochemical reaction by UV rays

  Vitamin D3 (Cholecalciferol) → UV dehydration of dehydrocholesterol

  1,25-dihydroxycholecalciferol (Calcitriol) → regulate calcium and phosphorus
• Ergocalciferol and cholecalciferol are not biologically active and are converted in vivo into its active form by two processes of hydroxylation

  
  

  The first hydroxylation occurs at the 25th position anad catalyzed by

  25-hydroxylase in the liver

  Product = Calcidiol or 25-hydroxycholicalciferol – the predominant form of Vitamin D in the plasma and the major storage form of Vitamin D

  
  

  It is further hydroxylzed at the 1st position by 25-hydroxycholecalciferol

  1-hydroxylase in the kidney

  Product = 1,25-dihydroxycholecalciferol or Calcitriol
• 1,25-diOH-D3: most potent vitamin D metabolite 

  → 25-hydroxycholecalciferol 1-hydroxylase increased: low phosphate and calcium → triggers PTH secretion
• Vitamin D deficiency = basal metabolic rate will decrease

  Children: rickets

  Adults: osteomalacia 

  Symptoms: bow-leggedness, delayed dentition and tetany 
• Vitamin D Toxicity is RARE 

  Curative for rheumatoid arthritis 

  Overdose: Intake of 20-25,000 units per day
• Vitamin E: Antioxidant in prevention of nonenzymic oxidation of cell components 

  → cosmetics and beauty products

  Form sperm in rats but not humans

  Cofactor → Cytochrome B and C
• Vitamin E are natural tocopherols 

  Most active form: alpha tocopherol 
• Sparing action of Vit A and carotene → Presence of Vitamin E increases the storage of Vitamin A in the liver
• Effects of Vitamin E

  Very Low Birth Weight (VLBW) infants: Hemolysis and retinopathy.

  Adults: Abetalipoproteinemia due to defective chylomicron formation, leading to Vitamin E deficiency
• Least toxic fat-soluble vitamin is Vitamin E

  no observed toxicity up to 300 mg/day
• Vitamin E is NOT stored in the liver 

  Absorbed in small intestine → require bile salts
• Vitamin K is needed for synthesis of prothrombin in the liver 

  Needed as a component of the Electron Transport System (ETS) → Coenzyme Q 

  Induces RNA formation for the synthesis of blood clotting proteins
• Naphthoquinone derivative 

  • Vitamin K1 or Phylloquinone – obtained from Alfalfa leaves 
  • Vitamin K2 or Farmoquinone – produced through bacterial action in the large intestines 
• Vitamin K antagonists: Dicuomarol, Heparin, and Salicylates
• True vitamin K deficiency is RARE 

  Decrease bacterial population = Hypoprothrombinemia

  Faulty absorption due to the lack of bile salts: Celiac Disease and Sprue Disease

  Intake of sulfa drugs for long periods of time due to destruction of bacteria in the large intestines 

  Profuse Bleeding → Lack of prothrombin 

  Hemorrhage neonatorum → Non-formation of prothrombin in the liver 

  Newborns: Single intramuscular (IM) dose of Vitamin K as prophylaxis against hemorrhagic disease
• Vitamin K is absorbed from the proximal portion of the small intestines requiring the presence of bile salts

  Water-soluble analogue does not require bile salts when given orally 
• Vitamin B1 is the only heat-labile out of the water-soluble vitamin B complex
• Vitamin B1: Thiamine; naturally occurring as chloride or hydrochloride

  Coenzyme; Needed for growth 

  Thiamine pyrophosphate: involved in the non-oxidative decarboxylation of pyruvic acid. 

  Lipothiamide pyrophosphate: serves as a hydrogen acceptor 
• Thiamine pyrophosphate (TPP): biological active form

  Pyrithiamine: pyridine analog; antivitamin (vitamin inhibitor)

  → Administration leads to thiamine deficiency
• Vitamin B1 deficiency

  Beriberi (polyneuritis): deficiency

  Dry beriberi: peripheral neurological deficit

  Wet beriberi: pitting edema + extreme thirst, cardiac dysfunction

  Infantile beriberi: mothers are deficient in thiamine

  Wernicke-Korsakoff’s psychosis → seen in alcoholics; treatable with thiamine supplementation
• Daily thiamine intake is related to carbohydrate intake
• Vitamin B2: Riboflavin

  → Ribitol: sugar-derived

  Coloured fluorescent pigment 

  Sensitive to decomposition 
• Vitamin B2: Stimulating action in the conversion of iodides into iodoprotein by the mitochondrial-microsomal structures of the thyroid gland
• Vitamin B2

  Flavin Mononucleotide (FMN) is synthesized from riboflavin via ATP-dependent phosphorylation

  Flavin Adenine Dinucleotide (FAD) is formed by transferring an AMP moiety from ATP to FMN

  These reactions are ubiquitous in tissues. 

  FMN and FAD serve as prosthetic groups in flavoenzymes or flavoproteins.
• Riboflavinosis: deficiency of Vitamin B2 → show manifestation not related to function

  Glossitis: magenta red inflamed tongue 

  Seborrheic dermatitis: shark skin appearance in nasolabial
• Vitamin B2 is absorbed in small intestine by Flavokinase

  Free riboflavin → cannot cross placenta (unless estrogen present)
• Vitamin B3 Niacin/ Niacinamide/ Nicotinic  acid 

  → synthesized from tryptophan (require pyridoxal phosphate)

  Function: Niacin nucleotide (NAD+) and NADP+ will serve as coenzyme
• Pellagra (Niacin Deficiency Syndrome)

  Corn is major source of diet, corn is tryptophan and niacin-poor 

  For every 60 mg of tryptophan, there is only 1 mg of nicotinic acid generated in the presence of the active pathway.
• In patients with Carcinoid Syndrome and Hartnup disease, Pellagra can occur
• Vitamin B5 Pantothenic acid

  Formation of coenzyme A → serves as prosthetic group

  Formation of acetylcholine 

  Synthesis of citrate and acetoacetate 

  Major source: egg, liver, yeast
• Vitamin B6 Pyridoxine/ Pyridoxal/ Pyridoxamine 

  Co-decarboxylase 

  Substrate for pyridoxal kinase 

  Coenzyme → used for transamination 

  Needed for conversion of tryptophan