Antioxidant Vitamins and Mineral Flashcards
The Free Radical Theory
Oxidative stress from ROS is a key mechanism underpinning Cardiovascular Disease (CVD) and cancer
- oxidation of LDL in atherosclerosis
- oxygen free radicals damage/mutate DNA
Benefits of ROS
Health and lifespan increasing factors increase ROS production in mitochondria
- responding to stress causes transcriptional changes (gives stress resistance)
Only at high ROS concentration does damage outweigh benefit
Vitamin A Deficiency
Common in developing world (1.7% of deaths in developing world due to deficiency)
Can cause blindness:
- Lack of retinol = poor vision (particularly in low light ‘night blindness’)
- Severe deficiency = blindness
Deficiency + excess Vitamin A cause foetal abnormalities
- pregnant women advised to not eat liver
Vitamin A in Vision
The ‘all-trans-retinol’ form of Vitamin A gets converted into ‘11-cis-retinal’ in the Retinal Pigment Epithelium
- 11-cis-retinal gets transported to rod cells where it attaches to Opsin to form Rhodopsin (acts as a photoreceptor and gets recycled into all-trans-retinol after activation)
Vitamin A regulating gene expression
Retanoic Acid (RA) and Retinoid X Receptors (RXR) form heterodimers which bind to RA Response Elements (RARE) - Heterodimer also interacts with Nuclear Receptors
Important in immune cell maturation
- deficiency increases susceptibility to infection
Vitamin K (Koagulation)
Required as a coenzyme for gamma-glutamyl carboxylases
- responsible for producing clotting factors II, VI, IX & X
- deficiency increases chance of haemorrhaging
Found in 2 forms:
1) Phylloquinone from plants
2) Menoquinone from intestinal bacteria (low levels in babies leads to deficiency)
Warfarin anti-coagulant
Acts as an anti-coagulant by inhibiting regeneration of Active Vitamin K
- inhibits the Vitamin K Epoxide Reductase Enzyme (VKORC1)
Uses:
- treatment following heart surgery
- rat poison (makes them haemorrhaging-prone, causing death if they get a knock etc. Some rats evolved though…)
Roles of Vitamin K other than coagulation
1) Osteocalcin
- required for growth/maturation of bone
2) Matrix Gla Protein (MGP)
- In cartilage, bone and soft tissue: involved in inhibiting calcium deposition
3) Periostin
- In connective tissue, involved in bone growth, remodelling and angiogenesis
Vitamin D synthesis
Synthesised from cholesterol:
1) 7-dehydrocholesterol to Cholecalciferol (D3) by UV light in the skin
2) D3 converted to 25-hydroxyvitamin D3 (inactive, circulating, abundant) in the Liver
3) In the Kidney, the inactive 25-hydroxyvitamin D3 is activated; being converted to 1,25-dihydroxyvitamin D3 (aka Calcitriol)
Vitamin D deficiency
Causes bone disease (Osteomalacia in adults, Rickets in children)
- Vitamin D = transcriptional regulator for synthesis of proteins involved in calcium homeostasis/bone growth
- It binds vitamin D receptors in the nucleus to increase Ca and phosphate absorption from intestine (mobilises Ca2+ from bone if dietary supply is low)
Role of Vitamin D in the Immune System
Auto-immune diseases/Cancer?
Enhances Innate Immune system (inhibits the Adaptive Immune system)
- blocks plasma cell differentiation
- Skews Th1/Th17 to a Th2 response
- alters cytokine production
Hence deficiency is implicated in auto-immune diseases
- also associated with cancer (esp colon)
- cancer incidence higher in low light (+ racial & genetic factors)
Iron distribution and role
Role:
- Component of electron carriers (e.g. Cyt P450)
- Component of Haem
Distribution:
- 1-2mg absorbed per day
- Similar amount lost through epithelial cell loss
- Transferrin transports iron in blood & delivers it to tissues
- Ferritin involved in iron storage (highly regulated)
Iron deficiency
Higher risk in young girls & women
- pregnancy and menstruation
Associated anaemia: Microcytic Anaemia
- RBC smaller (microcytic) and paler (hypochromic) in patient sample
- Haemoglobin seen in narrow band around periphery of erythrocyte (should be inside)
Iron absorption
Tightly controlled absorption as there are no mechanisms of removal (other than epithelial shedding)
- Tight control prevents haemochromatosis (excess iron storage)
- Hepcidin is key in controlling absorption
- Low iron levels in athletes and patients with Chronic inflammatory disease
Iodine in Thyroid Hormone Synthesis
1) Iodine imported into Thyroid follicular cell from blood
2) Iodine transported into follicular colloid
3) Thyroglobulin (histidine rich) is endocytosed into colloid area
4) Iodine gets oxidised and can iodinise tryrosine residues
5) Conjugation of 2 histidine residues to form T3 or T4
6) T3/T4 endocytosed into Thyroid Follicular cell
7) Protein can undergo proteolysis to release the thyroid hormone which can enter the blood stream
Iodine
Important in thyroid hormone synthesis, determining basal metabolic rate and essential for normal growth
Found in 2 forms:
1) Tetraidothyronine (T4)
- main circulating form, converted to T3 by deiodinase enzymes in target tissue (brain/liver)
2) Triiodothyronine (T3)
- Active form which binds to thyroid hormone receptors in nucleus to regulate gene expression
Iodine deficiency and measuring
During development = stunted growth and mental retardation (‘cretinism’)
An enlarged thyroid (‘goitre’) seen in adults
Levels measured using excretion levels
- lower urinary iodine excretion levels = higher deficiency
Calcium and deficiency
Normal roles in cell signalling, neural transmission, muscle formation, secretion…
Hypocalcaemia (deficiency)
- leads to muscle cramps & spasms - tetany
- increased risk of osteoporosis
Vitamin D and Parathyroid Hormone (PH) role in controlling plasma Ca2+ levels
PH secretion triggered by a drop in plasma Ca2+ levels via the Calcium Sensing Receptor (CaSR) in Parathyroid gland
- promotes Ca2+ release from bone
- increases Ca2+ reabsorption in kidney
- stimulates Vitamin D activation (increases Ca2+ absorption in intestines, increases bone’s response to PH and regulates PH release
Danger of excess vitamin/mineral intake
Iron overdose poisons children
Excess vitamin D causes hypercalcaemia
Vitamin A = teratogen and toxic in high amounts
Excess vitamin C causes kidney stones
