vitamins 2 Flashcards
what are vitamins
- chemically unrelated compounds
- cannot be synthesised by human body
- required in diet
fat soluble vitamins
- A, D, E, K.
- released, transported and absorbed in chylomicrons with dietary fat
- not readily excreted
- sig. qts in liver and adipose tissue
good source of folic acid
- leafy, dark green veggies
- wholegrains
- beans
function of folic acid
- tetrahydrofolate is the reduced coenzyme form of folate
- receives 1C fragments from donors
- synthesis of AA, purine nucleotides, thymidine monophosphate (pyrimidine nucleotide incorporated into DNA)
- deficiency = cant make DNA = can’t divide
cause of inadequate serum levels of folate
- increased demand (pregnancy, breastfeeding)
- poor absorption
- alcoholism
- treatment with drugs
- folate-free diet
how long does folate free diet take to cause deficiency
few weeks
what are common neural tube defects
- spina bifida
- anencephaly
how are common NTDs prevented
- adequate nutrition at time of conception as critical folate-dependent development occurs in 1st weeks
biomedical functions of vitamin B12
- remethylation of Hcy to methionine
- isommerisation of methylmalonyl CoA
one cause of neurological manifestations of B12 deficiency?
- methylmalonyl cOa produced during degradation of fatty acids
- if left un-isomerised, unusual branched FA accumulate + become incorporated into cell membrane, including those of CNS
sources of B12
- only micro-organisms, not made in plants
- liver
- red meat
- fish
- eggs
- dairy products
- fortified cereal
Explain the folate trap hypothesis
- methionine synthase uses B12 as coenzyme when converting 5-methylTHF into other forms of THF
- deficiency = folate cant be converted and is trapped = decrease in other forms of THF
- other forms required for purine and TMP synthesis = symptoms of megaloblastic anaemia
which cells are effects of cobalamin deficiency most pronounced?
- rapidly dividing cells:
- erythropoietic tissue
- mucosal cells
how long does cobalamin deficiency symptoms take to show
- several years as significant amounts stored in body IF due to intake
- more quickly if due to absorption
which test evaluates b12 absorption
schilling test
increased levels of what in blood indicate b12 deficiency
methylmalonic acid
How is cobalamin absorbed by the body?
- released from food in acidic environment of stomach
- free b12 binds to glycoprotein, transp to intestine
- pancreatic enzyme releases from R-protein, b12 binds to IF
- b12-IF complex travels through intestine, binds to cubulin receptor on surface of mucosal cells in ileum
- b12 transp into mucosal cell and subsequently general circulation.
- carried by binding protein transcobalamin
- taken up and stored by liver, released in bile, reabsorbed in ileum
cause of malabsorption of cobalamin in elderly
reduced secretion of gastric acid (achlorydia)
what is pernicious anaemia
severe malabsorption of cobalamin
common cause of pernicious anaemia
- autoimmune destruction of gastric parietal cells that absorb IF
- partial/total gastrectomy become IF deficient and therefore b12 deficient.
effects of cobalamin deficiency
- anaemic (folate recylcing impaired)
- neuropsychiatric symptoms as disease develops. CNS effects irreversible
treatment of pernicious anaemia
lifelong treatment of
- high dose oral b12 or
- IM cyanocobalamin
why does b12 supplementation work
- approx 1% cobalamin uptake is by IF-independent diffusion
active form of vitamin C
ascorbic acid
Function of vit C
- act as reducing agent.
- coenzyme in hydroxylation reactions. e.g. hydroxylation of proline and lysyl residues in collagen.
- thus, required for maintenance of normal connective tissue + wound healing.
- facilitates absorption of dietary non-haeme iron from intestine by reducton of fe3+ to fe2+
- antioxidant
- forms collagen, bile acids, epinephrine and steroid hormones
Vit C deficiency
- scurvy; bleeding gums, haemorrhage, fatigue, bone, joint, teeth
- can be explained by defective connective tissue
- also causes microcytic anaemia
what is vit b6 a collective term for
- pyridoxine, pyridoxal and pyridoxamine; all derivatives of pyridine
which b6 is found in plants
- pyridoxine
which b6 is found in animal derived food
pyridoxamine and pyridoxal
biochemical function of b6 supp
- precursors to PLP (coenzyme)
- e.g. transulfuration of Hcy to cysteine
- transamination
- deamination
- decarboxylation
- condensation
clinicals b6 deficiency
- isoniazid used to treat TB induces b6 defic. bc forms inactive derivative with PLP.
- administered in conjunction w b6 supplementation
- dietary deficiencies in newborns, women taking oral contraceptive, alcoholism
b6 toxicity
- excess of 400x RDA causes sensory neuropathy
what is thiamine
vit b1
active form of b1 and how is it formed
thiamine pyrophosphate TPP formed by transfer of pyrophosphate grp from ADP
biochemical functions of b1
- formation/degradation of alpha ketols
- oxidative decarboxylation of a-keto acids
beri-beri + classification
- thiamine-deficiency syndrome found inn areas where polished rice is major comp of diet
- dry: peripheral neuropathy esp in legs
- wet: oedema bc of dilated cardiomyopathy
Wernicke-korsakoff syndrome
- COAT RANK
- mental Confusion
- Opthalmoplegia: paralysis of eye muscles
- gait Ataxia
- caused by dietary insufficiency/impaired intestinal absorption of Thiamine
- Retrograde amnesia
- Anterogade amnesia
- Nystagmus
- Korsakoff psychosis + wernicke encephalopathy
why does b1 deficiency affect CNS
- oxidative decarboxylation of pyruvate and AKG is decreased
- less ATP produced
- impaired cellular function
what is niacin
vit b3.
niacin/nicotinic acid
biologically active coenzyme forms of b3
NAD+ and its phosphorylated derivative NADP+
distribution of niacin
- unrefined and enriched grains and cereal, milk and lean meats (especially liver)
what does niacin deficiency cause
-pellagra; disease involving skin, GIT and CNS.
- symptoms progress through 3 Ds;
- dermatitis (photosensitivity)
- diarrhoea
- dementia
- death if untreated
- Hartnup disorder (defective absorption of tryptophan) results in pellagra like symptoms
what type of diet causes pellagra
corn based as low in niacin and tryptophan
how is niacin used to treat hyperlipidemia
- niacin at 1.5g/day strongly inhibits lipolysis at adipose tissue
- reduces free FA circulating
- reduces TAG prod and therefore VLDL
- LDL derived from VLDL so also red
- particularly useful in type 11b hyperlipoporteinemia
- high naicin doses causes flushing, taking aspirin 30 mins prior can reduce effects
name of vitamin b2
riboflavin
biologically active forms of b2
- flavin mononucleotide FMN
- FAD formed by AMP moiety from ATP to FMN
biochemical function of b2
- both bind tightly to flavoenzyes can oxidise or reduce substance
- e.g. NADH dehydrogenase (FMN)
succinate dehydrogenase (FAD)
b2 deficiency
not associated w/ major human disease, but accompanies other vit deficiencies
- symptoms; dermatitis, cheilosis glossitis
what is b7 known as
biotin
biochemical imp of biotin
- coenzyme in carboxylation reactions: carrier of activated carbon
- coenzyme in gluconeogenesis+ citric acid cycle, fatty acid synthesis and propyl coenzyme synthesis
deficiency of biotin leads to
- anaemia
- loss of appetite
- hair loss
- nausea
- dermatitis
- depression
- halucinations
- muscle pain
sources vit b7
- widely distributed; liver, kidney egg yolk, tomatoes, grain
another name for b5
pantothenic acid
sources b5
- eggs
- liver
- yeast
active states vit b5
CoA; central molecule involved in all metabolisms eg dehydrogenation of pyruvate + AKG
natural form of vit A
retinol
what do the retinoids include
- retinol: storage form of Vit A, found in animal tissues. is a primary alcohol
- retinal: aldehyde derivative of retinol when oxidised
- retinoic acid: acid derived from oxidation of retinal. cannot be produced in body
- beta-carotene: plant foods contain it.
- AKA provitamin A.
- oxidatively cleaved in intestine to give 2 retinal molecules.
- has antioxidant activity
sources of vitamin A
- liver
- kidney
- cream
- butter
- egg yolk
- yellow, orange, daark green vegertables and fruits good sources of carotenes
vit A absorption and transport to liver
- retinyl esters -> retinol and FFA
- b-carotene -> retinal -> reduced to retinol
- both these retinols re-esterified in enterocytes using fatty CoA
- secreted as component of chylomicrons in lymphatic system.
- chylomicron remnants containing retinyl esters taken up by and stored in liver
release from liver
- retinol binding protein complexed with transthyretin transports retinol through blood
- binds to transp protein on surface of peripheral tissue cells, allows retinol to enter
retinoic acid mechanism of action
- retinol oxidised to retinoic acid
- binds to retinoic acid receptors RAR in nucleus
- retinoic acid-RAR complex binds to response elements on DNA and regulates RNA synthesis
- allows control of specific protein eg keratin
functions of vit A
- vision maintenance (retinoic acid not involved)
- epithelial cell maintenance - differentiation - mucus secretion - immune syst
- reproduction; supports spermatogenesis and prevents fetal resorption in females (retinoic acid not involved)
- bone growth
describe visual cycle vit A
- 11-cis retinal + opsin -> rhodopsin
- light + rhodopsin -> all-trans retinal + opsin
- all-trans retinal -> all trans retinol -> all-trans retinyl esters -> 11-cis retinol -> 11-cis retinal
effects of vit A deficiency
- earliest sign: nyctalopia (night blindness)
- prolonged deficiency = permanent loss of visual cells
- severe deficiency xerophthalmia ; untreated = blindness
what is xerophalthamia
- pathologic dryness of conjunctiva and cornea caused in part by inc keratin synthesis
- untreated -> corneal ulceration -> blindness due to formation of opaque scar tissue
which vit A is used to treat mild acne + skin aging
all-trans retinoic acid (tretinoin) oral too toxic
what is oral tretinoin used for
acute promyelocytic leukemia
what is isotretinoin used for
- severe cystic acne.
- is teratogenic, should be avoided in women of child-bearing capacity
how is psoriasis treated
oral synthetic retinoid
excess of vitamin A
- hypervitaminosis A
- skin dry and pruritic ( decreased keratin)
- liver enlarged - can become cirrhotic
- CNS-> rise in intracranial pressure can mimic symptoms of brain tumour.
- decreased bone mineral density + increased risk of fractures
- teratogenesis in pregnant women
which retinoid functions as a hormone
retinol
active form of vitamin E
alpha-tocopherol
function of vit E
- antioxidant in prevention of nonenzymic oxidations, eg oxidation of LDL and peroxidation of polyunsaturated FA
effect of vit C on vit E
C regenerates active vit E
sources of vit E
- vegetable oils rich source
- liver and eggs moderate source
vit E deficiency
- newborns can obtain from breast milk/supplements to prevent haemolysis and retinopathy
- in adults, usually due to defective lipid absorption/transport
- abetalipoproteinemia caused by defecr in formation of chylomicrons result in vit E deficiency
what is the least toxic fat sol vitamin
vit E
active molecule of vitamin D
- calcitriol
vit D distribution
- collagen synthesis intermediate converted to vit D3 in dermis + epidermis when exposed to sunlight, transp to liver by vit d-binding protein
- diet; vit d2 found in plants and vit d3 found in animal tissues. dietary vit D packaged into chylomicrons
how is vit d formed
- vit d2 + d3 converted to calcitriol by 2 sequential hydroxylation reactions
- 1st in liver forms calcidiol
- 2nd in kidneys form calcitriol
functions of vit D
- maintain adequate ca2+ serum levels
- inc ca2+ mobilisation from bone
- inc renal resorption ca2+
- dec renal excretion of ca2+
- inc intestinal absorption of ca2+
how does vit d increase intestinal absorption of calcium
- calcitriol binds to cytosolic receptor in intestinal cell and interacts w/ response elements on DNA
- increases gene expression of calbindin
sources of vit D
- fatty fish
- liver
- egg yolk
Vit D deficiency
diet causes:
- rickets in children - continual formation of collagen matrix but not mineralisation - soft and pliable bones
- osteomalacia in adults - demineralisation of bones increases susceptibility to fracture -bow legs
mutation in vit d receptor causes hereditary vit d-deficient rickets
Renal osteodystrophy causes, effects and treatment
- caused by chronic kidney disease
- decreased vit D formation, hyperphosphatemia and hypocalcemia
- low ca2+ = increase in PTH -> associated bone demineralisation
- treated with vit d supplementation + PO43- reduction therapy
what is hypoparathyroidism + treatment
- lack of PTH causes hypocalcemia and hyperphosphatemia as PTH increases phosphate excretion
- treated with vit D
Vit D toxicity symptoms
- loss of appetite
- nausea
- thirst
- weakness
- hypercalcemia - ca2+ deposits in soft tissue (metastatic calcification)
- excess vit d produced in skin is converted to inactive form so doesnt cause toxicity
principal role of vit K
- coenzyme in carboxylation of glutamic acid residues to gamma-carboxyglutamate (Gla) in post-translational protein modification
- req y-glutamylcarboxylase, O2, CO2, hydroquinone form of vit K (gets oxidised to epoxide form)
- Gla residues also used to form osteocalcin + matrix Gla protein in bones
active forms of vit K
- plants as phylloquinone (K1)
- intestinal bacteria as menaquinone (K2)
- menadione (synthetic form of vit K) can be converted to K2
what can inhibit formation of Gla residues
warfarin - synthetic analog of vit K (inhibits VKOR, enzyme req to regenerate functional form hydroquinone form of vit K
what blood clotting proteins is vit k involved in formation of
- prothrombin
- FVII
- FIX
- FX
vitamin K sources
- cabbage
- kale
- egg yolk
- spinach
- liver
- intestinal bacteria
vitamin K deficiency
- unusual as adequate amounts in diet and bacteria
- decrease in bacterial gut population eg by antibiotics -> leads to hypoprothrombinemia -> bleeding tendency therefore may need vit K supplementation
cephalosporin antibiotics have warfarin-like mechanism, inhibits VKOR - deficiency can also affect bone health
why can newborns have vit K deficiency
- sterile intestines + breastmilk provides only 1/5th of req amount
- therefore single intramuscular dose as prophylaxis against haemorrhagic disease of the newborn
Vit K excess
- prolonged admin of large doses of menadione can cause haemolytic anaemia and jaundice in infants due to RBC membrane damage
