Vitamins and Coenzymes 2

Vitamins and Coenzymes 2

• Source: Liver, kidney, yeast, lemons, bananas, strawberries and fresh green vegetables
• Content reduced 50-90% by cooking, also light sensitive

• Biological function: Folic acid reduced to tetrahydrofolate (THF; coenzyme F) by two enzymes using NADP as a coenzyme

• THF used to transger hydroxymethyl, formyl and methyl groups in a large number of reactions and significantly in the synthesis of purine and pyrimidine bases in the formation of DNA

• Caused by inadequate diet (body reserves are low), malabsorption, malignant disease, medication, alcohol abuse
• Megablastic anaemia: due to faulty red blood cell multiplication and maturation. Treatment with 5-20mg folic acid daily
• Supplements given in pregnancy, leukaemia and drug-induced folate deficiency. Prophylaxis with 0.2-0.5mg folic acid daily
• Supplements may mask B12 deficiency which results in damage to the nervous system

• Found in meat, shellfish, salmon, milk, cheese, eggs, fortified breakfast cereals
• Daily requirement only 1.5mg
• Forms the basis of two unstable coenzymes required in intramolecular rearrangement reactions
• Essential (with folic acid) for normal erythropoiesis
• Deficiency causes pernicious anaemia and degeneration of spinal cord

• Source: citrus fruits, green plants, tomatoes, potatoes
• Can be oxidised on cooking
• Water soluble

• Biological function: most powerful reducing agent known to occur naturally in living tissue, cofactor in numerous processes
• Collagen
  • Most common protein in vertebrates as the major fibrous element of skin, bone, tendon, cartilage, blood vessels and teeth
  • Contains two amino acids present in very few other proteins - hydroxyproline and hydroxylysine
  • The hydroxyproline in collagen is synthesised from proline
• Ascorbic acid maintains the iron atom (present at the active site of prolyl hydroxylase) in the ferrous state (Fe2+)

• The hydroxylation of proline is essential to provide more OH groups for H bonding which maintains the stability of the triple helix of collagen
• Hydroxylation of dopamine to noradrenaline
• Hydroxylation in steroid synthesis
• Electron donor in the conversion of folic acid to THF
• Iron absorption (Fe3+ to Fe2+)
• Antioxidant
• Role in fighting infection and in wound healing
• Possible reduced levels apparentin the common cold and cancer

• Scurvy characterised by swollen gums, bruising, haemorrhage, bone fracture, loose teeth, poor wound healing, anaemia
• Clinical trial on the effect of citrus juice on scurvy conducted on British sailors in 1747
• Supplements may benefit those not following a balanced diet (elderly, infirm), diabetics, pregnant and lactating women, heavy drinkers and smokers
• Toxicity: stomach complaints

• Source: milk, butter, cheese, liver (especially cod liver oil), added to margarine
• Retinol can be synthesised from carotenoids (found in carrots and tomatoes)

• Biological Function: converted to 11-cis-retinol (using NADP+ as a coenzyme) which is a photosensitive prosthetic group essential for normal retinal functional
• Vitamin A also has a role in the maintenance of normal growth, bone formation, repair of epithelial tissue and reproductive ability

• Still widespread in developing world
• Night blindness, dry and hyperkeratotic skin (retinoic acid used as psorioasis/acne treatment), skin infection, corneal damage and blindness
• Supplements may be required in breast feeding women to compensate for infant's supply and in patients unable to absorb or store lipids
• Toxicity: unborn children

• Vitamin D2 (calciferol, ergocalciferol)
• Vitamin D3 (cholecalciferol)
• Vitamin D4
• Source: Cholecalciferol present in butter, milk, cheese, egg yolk and fish liver oils, added to margarine and baby foods
• Body not dependent on dietary intake as vitamin D3 is formed under UV light from provitamin precursors (7-dehydrocholesterol) in the skin

• Biological function
  • Vitamin D is converted into active metabolites in the liver and kidney
  • The metabolites stimulate synthesis of specific proteins that act as Ca2+ carriers in bone and intestine increasing absorption of dietary Ca2+ and release of Ca2+ from bone (PO4- passively accompanies the Ca2+ movements)
  • Vitamin D maintains Ca2+ and PO4- at sites of new bone formation therefore is essential for proper formation of the skeleton

• Rickets in children characterised by distortion of the long bones of the legs and bones of the pelvis and spine
• Osteomalacia in adults (bone softening)
• Rate of synthesis of vitamin D in the skin depends on exposure to UV light therefore night workers and miners traditionally prone to deficiency
• Rate of synthesis of vitamin D in the skin also depends on skin pigmentation
• Toxicity: weakens the bones

• Vitamin E = family of compounds (the tocepherols and tocotrienols)
• Source: vegatable oils (sunflower, soybean and corn oil)

• Biological function
  • Acts as a fat-soluble antioxidant
  • Also involved in the function of nerve and eye tissue
• Deficiency
  • Haemolytic anaemia
  • Neuromuscular and neurological problems (e.g. myopathies)
  • Eye problems (e.g. retinopathy)
• Toxicity
  • Muscle weakness, fatigue, nausea and diarrhoea
  • The most significant risk is bleeding

• Vitamin K1 (phylloquinone)
• Vitamin K2 (manoquinone)
• Source: leafy green vegetables (spinach, cabbage, kale), gut flora can convert K1 into K2

• Biological functions: attaches a second carboxylic acid group onto the glutamate residues of a number of proteins to form a gamma-carboxyglutamate (Gla) residue
• This activates blood coagulation factors II (prothrombin), VII, IX and X, the anticoagulant proteinsC and S and protein Z
• Warfarin acts as a vitamin K1 antagonist
• Function of K1 and K2 identical

• Deficiency
  • Rarely due to lack of dietary intake
  • Malabsorption conditions can affect uptake
  • Symptoms include anaemia, bruising and bleeding at the mucosal membranes (e.g. gums, nose)
• Toxicity
  • Unlike most fat-soluble vitamins, not stored in great quantities in the liver
  • Therefore toxicity is not seen with higher doses of vitamin K1 or K2 in otherwise healthy people