MD140 Lecture 1 Feb 6th Lecture Canvas.pdf

MD140 Vitamins & Minerals 6th Feb 2024 Muriel Grenon, Biochemistry [email protected] MD140 Vitamins Minerals 2 lectures Session 1: Tuesday 6th Feb, 11am Session 2: Wednesday 7th Feb, 9am Learning Resources Similar to semester 1 MD140 Canvas Lecture slides Pre-recorded lectures avai...

MD140 Vitamins & Minerals 6th Feb 2024 Muriel Grenon, Biochemistry [email protected] MD140 Vitamins Minerals 2 lectures Session 1: Tuesday 6th Feb, 11am Session 2: Wednesday 7th Feb, 9am Learning Resources Similar to semester 1 MD140 Canvas Lecture slides Pre-recorded lectures available (easy to navigate) ‘Test your knowledge’ exercises Text-book: Lippincott’s Illustrated Reviews – Biochemistry Medical Biochemistry, 5th edition Baynes & Dominiczak Content Vitamins and minerals 1. General introduction 2. 2. Vitamins 2.1 General introduction to Vitamins 2.2 Fat soluble vitamins: A, D, E & K 2.3 Water soluble Vitamins : B family & C 3. Minerals (Folder 3) 3.1 General introduction 3.2 Major minerals 3.3 Trace and ultra-trace minerals MICRONUTRIENTS Vitamins and minerals essential for our metabolism Form prosthetic groups or co-factors of Enzyme Can act as hormones (Vit A & D) Important for cell growth, proliferation, differentiation and immune mechanisms Learning Objectives To describe the biological function of micronutrients and their necessity To explain the link between the biochemical function a given micronutrient and the pathophysiological consequence of its deficiency To discuss the consequences of micronutrient deficiencies 1. introduction on micronutrients Deficiency : Clinical syndromes can develop due to: Inadequate intake (malnutrition, illness) Inefficient utilisation Increased loss Poor absorption from intestinal tract (aging, surgery) Increased demand (adolescence, pregnancy) Multiple deficiencies more common than single Toxicity due to excess High risk patients for deficiencies Liver and renal diseases Undernourished Malabsorption e.g. Irritable Bowel Syndrome, Short bowel syndrome Substance abuse Geriatrics patients Chronic inflammatory disease DRI values are amount required to prevent deficiency and maintain optimal health Dietary Reference Intakes Established based on evidence from many types of research studies Specific for nutrients, life stage (age) groups, physiologic states and gender https://www.who.int/nutrition/topics/micronutrients/en/ EAR: Estimated Average requirement. Meet the requirement of 50% healthy population RDA = recommended daily allowance. Meet the requirement of 98% population 4 standards AI = Adequate intake. Estimate based on group of healthy people, used when no RDA known. You need to know the definitions of the standards and the magnitude of requirement but not the specific value UL= tolerable upper limit. Highest daily dose that pose no risk https://www.who.int/nutrition/topics/micronutrients/en/ 2. Vitamins Introduction Q1 Vitamins are chemically related compounds 1. True 2. False Vevox Q2 Vitamins are classified as Fat or Water soluble. This is stemming from their discovery in 1. 2. 3. 4. Blood Milk Citrus fruit Butter Q2 Vitamins are classified as Fat or Water soluble. This is stemming from their discovery in 1. 2. 3. 4. Blood Milk Citrus fruit Butter Vevox Q3 most Vitamins are found in each of the food groups below 1. True 2. False Vevox Q4 Part of the digestive system where vitamins absorption is maximal ? 1. 2. 3. 4. 5. Mouth Stomach Small intestine Large intestine Equally spread over the 4 above Vitamins In The Digestive Tract 40-90% of the vitamins are absorbed in the small intestine Vitamin Functions Vitamins promote and regulate body activities Each vitamin has a unique role B vitamins are all coenzymes Q7 Which one of the following vitamins dissolves in water? 1. 2. 3. 4. 5. Vitamin D Vitamin A Vitamin B1 Vitamin K Vitamin E FAT Soluble Vitamins Stored in Tissue, associated with body fat Circulating concentration constant and low. Best measured within cell for diagnosis Absorbed with Fat Deficiencies originating from: Fat malabsorption, diseases affecting liver or gallbladder, inflammatory bowel disease and Cystic Fibrosis. Water Soluble Vitamins Cannot be stored in body apart for Vitamin B12 MUST be regularly supplied in the diet Excess secreted in Urine 2.2. the 4 Fat soluble Vitamins Vitamin A Dietary compound Plant pigment Dietary compound Animal food Vitamin A: retinoids (1-3) Provitamin A: carotenoids (4) Collective term for several related biologically active molecules: Retinol and Retinal Retinoic Acid in its active form 1mg of retinol is equivalent to 12mg beta-carotene 2.2 FAT Soluble Vitamins. 1) Vitamin A 1) Vitamin A Vitamin A: retinoids: liver, fish oils, egg yolk, butter, milk Provitamin A: carotenoids: Dark greens, yellow veg and tomatoes 1mg of retinol is equivalent to 12mg beta-carotene RDA: 700 µg (micrograms) for women 900 µg for men Vitamin A: Retinal & the Visual Cycle Retinal (11-cis retinal) functions as prosthetic group of opsin to form rhodopsin 1- 2: One photon switch retinal to trans, and opsin conformation change 3 Nerve impulse and 4-6 retinal release Vitamin A deficiency can cause night blindness Severe deficiency causes blindness – most common cause in the world (developing world, liver disease, CF) Golden Rice: genetically engineered rice that produces beta-carotene. Finally approved for safe commercialisation in the Philippines in 2021 2.2 FAT Soluble Vitamins. 1) Vitamin A Vitamin A: key functions and toxicity Other Functions of retinoic acid due to acting as transcription regulator Binds nuclear receptor (RAR) Genes regulating growth, embryonic development and tissue differentiation Decrease Keratin synthesis in skin Antioxidant Medical treatment Excess is toxic and teratogenic Impossible to develop by ingesting normal food. Results of ingesting supplement or medical treatment 2) Vitamin D Normal dietary form is ergocalciferol (VitD2 in plant) and cholecalciferol (VitD3), calcitriol is the active metabolite made in kidney Cholecalciferol (Vit D3) is made in the skin from cholesterol by the action of UVB Good source : Fatty fish, liver, egg yolk. Not milk unless fortified 2) Vitamin D synthesis and role In the body Active Vitamin D formed by successive hydroxylation of D3 in Liver (calcidol) and Kidney (Calcitriol) Main Role: regulates calcium absorption and the balance between bones and blood Steroid hormone : binds to a nuclear receptor protein, forms a heterodimer with the vitamin A receptor. Increases expression of calcium binding protein genes. Achieves maintenance of calcium plasma concentration by 3 ways: Increased intestinal absorption Reduced excretion (by stimulating reabsorption in distal renal tubules of kidneys) Mobilisation of bone mineral Also needed to maintain normal function of parathyroid gland and the immune system 2) Vitamin D Deficiency Vit D Main Role: regulates calcium absorption and the balance between bones and blood. Steroid hormone Results in net loss of Calcium (soft bones) Rickets: insufficient mineralisation of bone and tooth matrix in children Osteomalacia : demineralisation of adult bones At risk: Population underexposed to sunlight o 30 min of arms and face exposure a day sufficient o Increased consumption if cannot be done Toxicity if excessive consumption Calcification of soft tissue Impossible to get through sun exposure 3) Vitamin E Dietary vitamin is a mixture of compounds called Tocopherols, only alpha-tocopherol is active for human functions primarily as a fat-soluble antioxidant Multiple roles: Involved in immune function, cellular signaling and gene expression. Inhibit PKC, affects cell adhesion and arachidonic acid metabolism. Also necessary for reproductive function in humans. Sources: Pure vegetable oils; egg yolk; wheat, wholemeal bread and cereals; nuts and sunflower seeds. RDA: 15 mg/day 3) Vitamin E is an Antioxidant Absorbed by small intestine with lipids (in chylomicrons and then secreted by liver as VLDL) Lipoproteins deliver vitamin E to the tissues Antioxidant role: Associated with all lipid-based cellular structure Vitamin E protects unsaturated fatty acids in cell membranes by neutralizing free radicals Deficiency: rare in adults (lipid misabsorption). Newborn (premature) at risk with hemolytic anaemia due to membrane damage of RBC 2.2 FAT Soluble Vitamins. 4) Vitamin K 4) Vitamin K Group of compounds that vary in the number of isoprenoids side chain K1: Circulating; K2: Hepatic store, K3: menadione Synthetic form Absorption depend on ability to absorb fat Co-Enzyme with role in blood clotting 2.2 FAT Soluble Vitamins. 4) Vitamin K 4) Vitamin K Diet: Green leafy veg, fruits dairy products, vegetable oils and cereals Can be synthesized by intestinal microflora AI: 90 to 120 ug/day Deficiency: Dietary deficiency does not occur except for newborn Deficiency with liver disease or fat malabsorption 4) Vitamin K In The Body A coenzyme for post-translational modification of coagulation factors Carboxylation of a specific glutamic residue by vitamin-dependent enzyme For example the production of thrombin (10 residues carboxylated to bind calcium) Maybe involved in health of bones and blood vessels Warfarin: Used for treating thrombosis-related disease (deep vein thrombosis, pulmonary thromboembolism…) Inhibitor of Vitamin K action (antagonist) Rat poison 3 Water soluble Vitamins A. Hematopoietic Folic Acid (B9) Vit B12 B. Energy Releasing Vit B1: Thiamine Vit B2: Riboflavin Vit B3: Niacin Vit B7: Biotin Vit B5: Panthotenic Acid The family of B Vitamins C. Other Vit B6 family: Pyridoxine, Pyridoxal, Pyridoxamine B family Hematopoietic Vitamins B9 & B12 Vitamin B9 – Folic Acid Folate, family of compounds Participates in: o Single Carbon transfer reactions (methylation) o Synthesis of choline, serine, Glycine and methionine o Synthesis of purines and pyrimidines Vitamin B9 – Folate: Common Deficiency Pregnancy and Lactation Requirement for dividing cells Requirement with increased blood volume Neural tube defects (NTD) (spina bifida and anencephaly), low birth weight, premature birth Vitamin B9 Folate deficiency: Adult Megaloblastic Anemia Presence of large cells in bone marrow Due to defect in Nucleic acid synthesis Loss of appetite, diarrhea, weakness Cannot be distinguished from Vitamin B12 deficiency Vitamin B12 (Cobalamin) Structure: Heme Ring AND Cobalt Ion Stable with the Cyano group, removed in active form CoEnzyme, Participates in: Nucleic acids synthesis Succinyl-CoA synthesis in FA metabolism Methionine metabolism with Folate: Methionine synthesis and Folates recycling Can only be synthetized by Bacteria Diet: meat, milk, eggs, fish. No vegetal source. Can be an issue for vegan diet. RDA: 1.8 to 2.4 mg/day Vitamin B12 Deficiency Neurological manifestations of deficiency: o abnormal FAs accumulate and incorporate into cell membranesincluding nervous system membranes o Numbness, loss of balance, confusion, mood distortion and dementia Like B9 def, Macrocytic or megaloblastic anemia B12 is needed to convert folate into that form, which is active for DNA synthesis indistinguishable from that seen in folate deficiency. Vitamin B12: Complex absorption & transport Stored in Liver under 3 forms Complex absorption and transport via interaction with specific proteins Special handling required: o Stomach acid and B12 binds R proteins o Pancreatic enzymes free B12 to bind intrinsic factor in Small intestine o In Ileum, B12-IF absorbed o B12 synthetised by microorganism in large intestine cannot be absorbed Vitamin B12 Deficiency – population at risk Patients with pernicious anemia (autoimmune disorder resulting in gastric atrophy and no IF) People with atrophic gastritis: low or no stomach acid People with Bariatric surgery Hypochlorydria due to age Vegan Taking high doses of folate supplements can mask vitamin B12 deficiency symptoms (but lead to neurological damage) Tomorrow Remaining Soluble vitamins Watch videos 2.3.1 and 2.3.2 Minerals