Week 6 Flashcards
What are vitamins?
Essential micronutrients
• must be provided by dietary source
• compounds not synthesized by the host in amounts adequate to meet normal physiological needs
Organic compounds
• Distinct from other essential micronutrient minerals
• Distinct from other organic compounds in the diet, i.e. macronutrients (fats, carbohydrates, and proteins)
Natural components of foods, present in minute amounts
• Low intakes can cause deficiency diseases
Water-soluble vitamins
- not readily stored - easily excreted
- consistent daily intake is important
- many synthesised by bacteria
Lipid-soluble vitamins
- can accumulate in body
- more likely to lead to hyperviterminosis
Functions of vitamin A
- vision
† Retinal binds to opsin to form rhodopsin in rods, iodopsin in cones
† Essential for signalling - control of gene expression via transcription factors
† Binding of retinoic acid activates receptors (RAR/RXR)
† RAR/RXR bind DNA
† Activate/repress gene expression
Vitamin A deficiencies
• Vision
† Nightblindness,
† Xerophthalmia (conjunctival ulcers)
• Teratogenic
† Excess is also teratogenic
† Crucial role of the Hox genes in embryogenesis
• Impaired immunity
• Anaemia
• Ostopenia
• Inappropriate bone depositio
Vitamin A toxicity
Causes
• Rarely from diet – sometimes consumption of animal livers
• Medication - 13-cis-Retinoic Acid (brand name ”Accutane”) can be used therapeutically to treat acne
Teratogenic
• Vitamin A effects expression of genes involved in embryogenesis
Idiopathic increased intracranial pressure
• Headache
• Vomiting
• Impairedconsciousness
Role of Vitamin D in Ca2+ homeostasis
• Vitamin D is involved in Ca2+ homeostasis
† Mediated by parathyroid hormone (PTH) – senses low Ca2+
• PTH promotes formation of active Vitamin D
† Negative feedback loop – High calcitriolàinactive PTH
† Homeostatic regulation
• Mechanisms:
†Renal reabsorption
† Intestinal absorption
† Mobilisation from bone (osteoclasts)
Vitamin D deficiency
Causes
• Provitamin D malabsorption
• Lack of UV
Osteomalacia (rickets)
• Low Ca2+
• Soft, pliable bones
• Impaired ossification
Vitamins K
K1 (phylloquinones)
K2 (menaquinones)
Found in plants
• e- acceptor in photosynthesis Converted from K1 by bacteria
• Found in fermented foods
Breaks naming convention
• named for German term meaning “coagulation vitamin”
(Koagulationsvitamin)
Function of Vitamin K: Gla proteins
Needed to activate Gla proteins
• Vit K is oxidised to quinone form
• Provides reducing power – acts as a cofactor for a carboxylase enzyme
• Adds a second carboxyl group to glutamic acid of certain proteins
• Glu residues → Gla residues
Effect
• Gla proteins can bind Ca2+
• Many proteins need to be carboxylated on glutamic acid residues to be active
To recycle oxidized Vitamin K it is reduced by 2 additional enzymes
Examples of Gla proteins
Blood coagulation
• Procoagulant: prothrombin (factor II), factors VII, IX, X
• Anticoagulant: proteins C, S, Z
Bone metabolism
• Osteoblast activity: Osteocalcin (Bone Gla Protein)
• Bone mineralisation: Matrix Gla protein (MGP)
Metabolism of blood vessels
• Arterial calcification: MGP
Tissue remodeling, cell fate changes
• Wound healing: Periostin
Vitamin K deficiency
Causes
• Abundant in diet, rare
• Lipid malabsorption
• Anticoagulant therapy
• Antibiotic therapy
Blood clotting disorders
• Important role of Gla proteins in coagulation factors and anticoagulant proteins
• Dangerous in newborns – injection given after birth
Osteoporosis
• Decreased activity of osteoblasts
Warfarin is a Vitamin K antagonist
• Over dose can be treated with Vit K
Vitamin E (tocopherol)
A family of tocopherols
(α-, β-, Ɣ-, δ-)
α-tocopherol
• highest biological activity
• most common
Dietary source
• Vegetable oils
Lipid Peroxidation
Caused by free radicals
• Fenton reaction (Fe2+) produces hydroxyl radical (OH-)
• Byproduct of metabolism
• Oxidative burst of immune cells
Lipid peroxidation is a chain reaction
• Oxidation of one lipid forms a free radical, oxidises further lipids
Targets
• PUFAs in biological membranes are susceptible
Vitamin E function
Enzyme cofactor
• α-tocopherol quinone acts as a cofactor of mitochondrial unsaturated FA synthesis
Antioxidant
• Stops free radical chain reactions
• Sacrificially oxidised to tocopheroxyl
• Can be recycled (reduced) back to tocopherol
Vitamin E deficiency and toxicity
Causes of deficiency
• Rarely from diet
• α-TTP mutations
• Fat malabsorption
• Peripheral neuropathy (Neurons: High levels of PUFA, Iron)
• Anemia, RBClifespan (RBC: High levels of PUFA)
Supra-physiological doses
• Stimulate immune system (e.g. Antibody production, mechanism is unclear)
• Cardiovascular health (Prevents oxidation of LDLs → involved in atherosclerosis)
Toxicity
• Rare, can tolerate large doses
• Antagonise functions of other fat - soluble vitamins (e.g. bleeding (VitK)