Vitamins Lecture Notes PDF

Vitamins Dr Rich Boden BIOL131(Z): Cells: The Building Blocks of Life (2024/25) @bodenlab  vitamins and steroids - cautions Please refrain from popular science books on the subject of vitamins – they’re almost all aime...

Vitamins Dr Rich Boden BIOL131(Z): Cells: The Building Blocks of Life (2024/25) @bodenlab  vitamins and steroids - cautions Please refrain from popular science books on the subject of vitamins – they’re almost all aimed at the desperate to get them to buy specific vitamins for hard to treat, painful, debilitating conditions like e.g. lupus, Ehlers-Danlos syndrome, fibromyalgia etc, promising miracles. Avoid! I’m afraid it’s proper textbooks and journal articles etc only for this lecture really, sorry! Do not waste your time trying to learn the chemical structures given herein – they are there to show you properties, not to be learned by rote! Please note because of the diversity of degree programmes taking this module, I’ve tried to include something for everyone where I can, which means I won’t necessarily pick up every single point on every the slides in the lecture itself, but they are still all there for you to learn from, of course.  vitamins and steroids - outline We will look at hypovitaminoses only where they are well-recognised and fairly commonplace – not for every vitamin. We will not always consider every vitamer or provitamin in detail. general terminology/groupings vitamins A, D, E and K, their hypovitaminoses, sources, roles in vivo, properties, provitamins, vitamers etc vitamin C and its hypovitaminosis, sources, properties, roles in vivo, vitamers etc. B-complex vitamins (9×), key roles in vivo e.g. enzyme cofactors made from them, hypovitaminoses (in name only), pathways they are needed for etc. We will only consider sources for a few.  definition and groupings Organic molecules needed in small amounts for the proper functioning of an organism. Actual needs vary by taxon – e.g. some vitamins are needed in the diet of Homo sapiens subsp. sapiens L. but can be made (or aren’t used at all) by other organisms. fat soluble vitamins: vitamin A, vitamin D, vitamin E, vitamin K water soluble vitamins: B complex vitamins (9×), vitamin C provitamins are precursors to vitamins themselves. vitamers are different forms of a vitamin (‘vitamin isomers’). Often measured in IU (international units) in nutrition and medicine, but mg/L, mM etc in biochemistry/etc – IU is defined as a different mass for each vitamin. To help you navigate the minefield of literature – there are a lot of old terms for some vitamins and other substances – here is a list of most of the things you may come across [DO NOT SIT AND LEARN THIS!]: There is no “vitamin F” (used for linoleic acid i.e. C16:2 ω6c ω9c) – this is a term invented recently by the skincare industry based on an old study from 1923 that suggested linoleic acid was a vitamin: disregarded in 1932! There are also no vitamin J (catechol or choline), vitamin L (anthranilic acid), vitamin P (flavonoid pigments), vitamin S (salicylic acid) or vitamin U (S-methylmethionine) Riboflavin, biotin and folate in the B complex used to be vitamin G, vitamin H and vitamin M, respectively. Some variation by country – e.g. in Francophone countries, vitamin B8 is the sugar alcohol myo-inositol, and so biotin is vitamin B7 [vitamin B8 in rest of world]. Be careful when you’re reading!  fat soluble: Vitamin A all vitamers are isoprenoids. ‘All-trans’ versions are usual in diet etc and only change to cis when in use. Essential vitamin of all Chordata. retinol (all-trans) vitamers: retinoic acid, retinaldehyde (retinal), retinol, retinyl esters. provitamins: β-carotene, α-carotene, γ-carotene etc, obtained from plants (cf. Mitochondria and Plastids lecture) and retinyl esters from meats. retinaldehyde (all-trans) retinaldehyde (retinal) is used in the eye to form rhodopsin, needed in low-light vision. Also made in some Archaea such as Halobacterium spp. for light-driven salt pumps/proton pumps based on retinal. retinyl palmitate [ester of palmitic acid and retinol] and carotenes are main forms in our diet, converted to retinol in small intestine. Retinol retinoic acid (all-trans) is the storage form. retinoic acid is synthesised from retinol in male gonads (needed for sperm generation) and in embryos (regulates brain development). Used β-carotene as pharmaceutical (Tretinoin®) for reversing photoaging of skin, treatment of acne (makes keratinocytes shed) and some cancers. cod liver oil (0.3 g/kg retinyl palmitate), sweet potato (9 mg/kg carotenes), carrot (8 mg/kg carotenes). supplement is usually β-carotene as retinol etc are toxic if too much is taken orally. Hypervitaminosis A can kill (cf. toxicity of Ursus 1 % retinol maritimus Phipps liver - 6 g retinol/kg). in squalane  hypovitaminosis A xerophthalmia – thickening of surface layers of the eye. keratomalacia – similar with inability to synthesise specialist tissues of eye surface – opaque cornea develops. nyctalopia (night blindness) – lack of retinaldehyde (and thus rhodopsin) in retina. xerophthalmia owing to hypovitaminosis A photophobia – aversion to bright light owing to lack of light-absorbing rhodopsin in retina. weight loss 500,000 children go blind each year worldwide from hypovitaminosis A – a GM product ‘golden rice’ was developed to prevent this by providing β-carotene to rice-dominant diets. ‘golden rice’ that produces β- ‘flecked’ retina owing to Has never been used owing carotene (GM food designed to hypovitaminosis A to groups like Greenpeace reduce eye disorders in developing who oppose GM crops. world) – developed late 1990s  carotenoids in the Aves For those taking BIOL132Z, Dr Collins will pick this up in her lecture on the Aves (Thu 5th Dec 2024) to give you a broader context on feather colouration and you should cross-relate the lectures with this module too! dietary uptake of carotenoids by the Aves comes from all 3 Domains of Life (Bacteria, Archaea and Eukarya) that they eat. EXAMPLE: Phoenicopterus spp. (greater flamingos) live in hypersaline lakes – their red-pigmented feathers have been shown to contain: bacterioruberin – produced by extremely halophilic Archaea of the Class Halobacteria in the Phylum Methanobacteriota such as Halococcus spp. and Halobacterium spp. Phoenicopterus ruber L. showing distinctive crimson echinenone – produced by Bacteria viz. members of the Phylum colouring Cyanobacteriota (marine biologists will know this pigment from [Gr. masc. n. φοῖνῐξ (phoînix), crimson, purple; Gr. neut. n. πτερόν (pterón), wing, feather; the orange interiors of the Echinoidea of the Metazoa!) N.L. masc. n. Phoenicopterus, he who has crimson wings/feathers; L. masc. adj. ruber, astaxanthin – produced by Eukarya viz. members of the Phylum red] Chlorophyta of the Viridiplantae. This is used widely as a food Eukarya > Metazoa > colouring (E161j). Chordata > Reptilia > Aves > Phoenicopteriformes > [Yim et al. (2015) Sci Rep 5: 16425] Phoenicopteridae  fat soluble: Vitamins D all are secosteroids (‘broken’ steroids). vitamers: ergocalciferol (D2), cholecalciferol (D3), 22- ergocalciferol dihydroergocalciferol (D4), sitocalciferol (D5). (D1 isn’t a (vitamin D2) thing!) produced (D3) in the stratum basale layer of the skin of Mammalia by a photodependent pathway (λ = 290-315 nm). D2 cholecalciferol is produced in Fungi in same way. (vitamin D3) regulates intestinal calcium uptake. Hypovitaminosis D is not uncommon in people: living in countries far from the equator; with Fitzpatrick Type V and VI skin; with very low body fat; whose skin seldom sees direct sunlight without SPF; [standard domestic window glass absorbs a lot of 290-315 nm light, but not all of it! so yes, you do still need to wear SPF indoors!] UK government recommends all adults take 10 μg/day year- round. 15 μg/day US/Canada. Higher doses may be needed (25 µg/day) for those with Fitzpatrick Type V and VI skins. cod liver oil (25 μg/kg), mushrooms (110 μg/kg if UV-exposed, 3 μg/kg otherwise), canned tuna (68 μg/kg).  hypovitaminosis D rickets – bone softening in children. Called osteomalacia in adults. osteoporosis – bones become porous and fragule. clinical depression and clinical anxiety – common symptoms of early stages of hypovitaminsis D. schizophrenia – not necessarily a symptom but many patients therewith have low serum vitamin D levels. Cause or effect? classical bow-legs in rickets muscular pain muscle twitching severe rickets in juvenile Homo sapiens subsp. sapiens L. Canis lupus subsp. familiaris L. with rickets bone density changes in osteoporosis  fat soluble: Vitamin E eight vitamers – 4 are tocopherols, 4 are tocotrienols. Names are prefixed with α, β, γ, α-tocopherol δ. Supplements usually use α-tocopheryl acetate as it’s more stable in long-term storage. potent antioxidants (aka reducing agents) – α-tocotrienol heads can donate electrons and hydrogens to oxidising agents e.g. reactive oxygen species (ROS). Important in handling oxidative stress. Protects cell membranes. hypovitaminosis E causes neurological damage (as ROS can’t be stopped!) but very rare – only occurs if dietary lipid uptake is not functioning. wheat germ oil (1.5 g/kg), oily fish (15 mg/kg), rapeseed oil (175 mg/kg).  fat soluble: Vitamin K two vitamers – phylloquinone (K1) and menaquinone (K2) – menaquinones (MKs) are respiratory chain quinones in many Bacteria and Archaea e.g. MK-4, MK- 7 – we obtain them from our gut microflora, like Escherichia coli, which leaks them into the gut. K1 is found in photosynthetic electron transfer chain in the K1 Viridiplantae and green leaves are best dietary source. Refer to plastid/phototrophy lectures! K2 MK-4 hypovitaminosis K causes issues with blood clotting and with proper Ca metabolism. needed for enzymes that carboxylate glutamine residues in some proteins to form carboxyglutamate – key in blood clotting cascades in Homo sapiens subsp. sapiens L. K2 MK-7 some evidence of a positive effect on bone density, particularly if taken with vitamin D3 (“vitamin D + K2” mixed supplements are now abundant!) various rodenticides work by preventing vitamin K being recycled – organisms bleed to death. K1 – dark green leafy vegetables (4-5 mg/kg); K2 – fermented soy beans e.g. 納豆 (natto, 10 mg/kg); goose meat (0.3 mg/kg); Our gut Bacteria make it for us!  water soluble: Vitamin C 2 vitamers: L-ascorbic acid (L-ascorbate) and dehydroascorbic acid (dehydroascorbate). oxidised form is L-ascorbic acid, dehydroascorbate must be reduced back at the expense of e.g. ascorbic acid glutathione. there are synthetic variations e.g. 3-O-ethyl ascorbate used particularly in skincare/haircare etc as more stable. potent antioxidant (reducing agent) – key in handling oxidative stress within the cytoplasm or in extracellular fluids (cf. vitamin E which does same in membranes). Used in vitro in culinary settings to stop oxidation of o-quinones by air in cut apples! enzyme cofactor e.g. hydroxylases involved in collagen biosynthesis. hypovitaminosis C is scurvy. rosehips (4 g/kg), blackcurrents (2 g/kg), kale (1.2 g/kg) citrus fruit (0.3-0.5 g/kg).  hypovitaminosis C overarching condition is scurvy but not all symptoms are always seen at once. bleeding gums rashes fatigue generalised muscle pains from lack of carnitine production. bleeding gums in scurvy patient anemia from low erythrocyte production. easy bruising wounds not healing neuropathy jaundice dry mouth, eyes and other orifices – dry mouth leads to dental caries, mouth ulcers etc blue-red spots around hair follicles personality changes edema  water soluble: thiamine (B1) various enzyme cofactors are made from it – e.g. ThPP in the pyruvate dehydrogenase complex (link reaction). essential for many Bacteria. hypovitaminosis B1 is beri-beri grains, meat, food, yeast… yeast extract (Marmite) was sent by Red Cross to POWs thiamine in WW2 on rice-only diets in Far East to provide thiamine. water soluble: riboflavin (B2) enzyme cofactors are made from it – e.g. flavins FMN/FMNH2 and FAD/FADH2 essential for many Bacteria. hypovitaminosis B2 is ariboflavinosis milk, eggs, meat, green vegetables, legumes… can be visually seen excreted in urine if there is an excess. riboflavin  water soluble: niacin (B3) enzyme cofactors are made from it e.g. NAD+ and NADP+. vitamers: niacin (nicotinic acid), niacinamide (nicotinamide), niacinamide riboside essential for many Bacteria. hypovitaminosis B3 is pellagra niacin meat, red fish, grains… water soluble: pantothenic acid (B5) provitamin: panthenol enzyme cofactors are made from it – e.g. coenzyme A (CoA). essential for many Bacteria. hypovitaminosis B5 is almost unheard of. pantothenic acid milk, eggs, potato, tomato, oats…  water soluble: pyridoxal 5ʹ-phosphate (B6) enzyme cofactor itself in many enzymes. vitamers: pyridoxine (PN), pyridoxal (PL), PL 5- phosphate, PN 5-phosphate, pyridoxamine (PM), PM 5- phosphate and others… essential for many Bacteria. hypovitaminosis B6 causes skin and neurological issues. pyridoxal 5ʹ-phosphate meat, red fish, grains… water soluble: biotin (B7) enzyme cofactor itself in many carboxylases. regulates gene expression in some ways. essential for many Bacteria. hypovitaminosis B7 causes rashes, hallucinations etc. biotin meat, eggs, yeast, legumes…  water soluble: folic acid, folate (B9) involved in DNA biosynthesis. essential for many Bacteria. hypovitaminosis B9 causes anaemia and B12 uptake issues as well as neural tube development issues during pregnancy. folic acid seeds, legumes, grains, green vegetables water soluble: p-aminobenzoic acid (B10) key in folate synthesis in Viridiplantae and Bacteria. essential for many Bacteria. hypovitaminosis B10 is unheard of, as a rule. gut Bacteria make it on our behalf. p-aminobenzoic acid probably not a vitamin for Homo sapiens subsp. sapiens.  water soluble: cobalamins (B12) involved in amino acid biosynthesis, fatty acid biosynthesis and DNA biosynthesies. Cofactor in many methyltransferases and isomerases. vitamers: cyanocobalamin, methylcobalamin (MeB12), hydroxycobalamin, adenosylcobalamin (adoB12) MeB12 and adoB12 are the active forms in the Mammalia – the other forms are converted once ingested. MeB12 is found in the cytosol; adoB12 is found in mitochondria. structure based on a corrinoid ring with bound Co+ ion (cf. the porphyrin ring with bound Fe2+ in heme). essential for many Bacteria but only routes of production in Nature are by (other) Bacteria and Archaea. herbivores obtain it only from Bacteria on the surface of plants. hypovitaminosis B12 causes anaemia, fatigue, joint pain, reduced heart function, depression and psychosis but is relatively rare in most people – usually caused by medication inhibiting uptake can be supplemented by intramuscular injection or transdermal patch if gastric absorption is failing. meat and fish are key dietary sources. A few algae do accumulate it but are not reliable dietary sources. Note that “Spirulina” (really a trade- name for 2 species of the “Cyanobacteria”) don’t make it – they make B12 structure solved by Prof Dorothy pseudovitamin B12 which humans cannot use at all. Hodgkin FRS (1910-1994), for which she won 1964 Nobel Prize in Chemistry. (Hodgkin et al. (1955) Nature 176: 325)  You should be able to: Give the key symptoms of each hypovitaminoses A, D and C. Give the provitamins and vitamers of vitamin A, stating which is used in the eye and in which molecule. Recognise vitamers of vitamin A from a diagram. Give three in vivo functions of vitamin A. State which vitamers of vitamin D are produced by the Mammalia and by the Fungi and which wavelengths of light are required. Give the in vivo function of vitamin E. List the vitamers of vitamin E. Give the vitamers of vitamin K, stating which is produced where. Give two key in vivo roles of vitamin C. Name hypovitaminoses B1, B2 and B3. State which enzyme cofactors are produced from B2, B3 and B5. Name the forms of B12 found in cytoplasm and mitochondria. Name enzyme groups that biotin and cobalamins are required for.  Supplementary Self Test 1. Give the key symptoms of hypovitaminoses A. 2. List the provitamins and vitamers of vitamin A. 3. Which vitamin A vitamers is essential for sperm production in Homo sapiens L.? 4. What vitamin A vitamer is used as a prescription-only medication for wrinkles for knackered old academics? 5. What wavelength range of light is required for vitamin D production, and which vitamers are formed in the Fungi and the Mammalia? 6. What in vivo property is common to vitamin C and vitamin E and where in a cell do they perform it? 7. Which vitamin K vitamer is produced in the gut of Homo sapiens L. and what by? 8. What is hypervitaminosis B1 better known as? 9. State which enzyme cofactors are produced from B2, B3 and B5. 10. Name the forms of B12 found in cytoplasm and mitochondria.  Supplementary Self Test ANSWERS 1. Give the key symptoms of hypovitaminoses A. Night-blindness, photophobia, ‘flecked’ retina, dry eyes, opaque cornea, weight loss. 2. List the provitamins and vitamers of vitamin A. provitamins: carotenes (α-, β- and γ-) and retinyl esters e.g. retinyl palmitate. vitamers: retinol, retinaldehyde (retinal), retinoic acid. 3. Which vitamin A vitamers is essential for sperm production in Homo sapiens L.? retinoic acid 4. What vitamin A vitamer is used as a prescription-only medication for wrinkles for knackered old academics? retinoic acid (drug name Tretinoin) 5. What wavelength range of light is required for vitamin D production, and which vitamers are formed in the Fungi and the Mammalia? 290-315 nm. 6. What in vivo property is common to vitamin C and vitamin E and where in a cell do they perform it? Both are antioxidants. Vitamin E performs it within the cell membrane and vitamin C performs it within the cytoplasm. 7. Which vitamin K vitamer is produced in the gut of Homo sapiens L. and what by? Vitamin K2, produced by gut Bacteria. 8. What is hypervitaminosis B1 better known as? Beri-beri 9. State which enzyme cofactors are produced from B2, B3 and B5. B2: FMN/FMNH2 and FAD/FADH2; B3: NAD+/NADH and NADP+/NADPH; B5: coenzyme A. 10. Name the forms of B12 found in cytoplasm and mitochondria. methocobalamin is found in the cytoplasm and adenosylcobalamin is found in mitochondria.