What are the two types of vitamins?
water soluble (precursors for coenzymes) and lipid soluble
What is the enzyme, pathway and deficiency of Biotin?
main pathway it activates: carboxylation
What is the enzyme, pathway and deficiency of thiamine (B1)?
main action: decarboxylation
ophthalamoplegia: eyes can't follow beam of light
Dry beri-beri: polyneuritis; occurs first, neurologic problems
What is the enzyme, pathway and deficiency of niacin (B3)?
coenzyme: NAD(H), NADP(H)
main action: oxidation/reduction
pellagra: nutritional problem
What is the enzyme, pathway and deficiency of folic acid?
coenzyme: THF (tetrahydrofolate)
main action: 1 carbon carrier; donor
megaloblastic anemia: large nucleated red cells in the marrow
What is the enzyme, pathway and deficiency of cyanocobalamin (B12)?
coenzyme: methyl-cobalamin and deoxyadenosyl-cobalamin
What is the enzyme, pathway and deficiency of pyridoxine (B6)?
coenzyme: pyridoxal P (PLP)
main action: transamination
delta aminolevulinate synthase: need b6 (no poryphin so heme not made properly)
isoniazid therapy: treat Tb; binds B6 so can't be absorbed
sideroblatsic anemiaa: Fe stays in the mitochondria becuase heme not formed properly
Heme: red because porphyrin
What is the enzyme, pathway and deficiency of riboflavin (B2)
--when it absorbs light, it degrades; consider with children using phototherapy
main action: oxidation/reduction
**cheilosis or stomatosis
What is the enzyme, pathway and deficiency of ascorbate (C)?
only water soluble vitamin without coenzyme
main action: antioxidant**scurby: ecchymoses, hyperelastic skin, loose teeth
What is the enzyme, pathway and deficiency of pantothenic acid
main action: carrier of fatty acid, HMG, acetate
Describe scurvy in an infant.
2-10 months old
bottle fed with formula that is overheated for pasteurization and not supplemented with Vitamin C
--Vitamin C is destroyed by excessie heat
gum bleeding doesn't occur unless erupted teeth
vitamin C: cofactor for proline and lysine hydroxylases in collagen syntehsis
--vitamin C deficiency--> collagen fibers less stable than normal
What are the other roles of vitamin C?
reducing iron in intestine to enhanble iron absorption
hepatic synthesis of bile acids
What are the four lipid soluble vitamins?
A, D, E, and K
A, D: work through enhancer mechanisms
What are the important functions of vitamin D?
What are the important functions of vitamin A?
What are the important functions of vitamin K?
What are the important functions of vitamin E?
How does vitamin D regulate calcium homeostasis?
hypocalcemia-->PTH release-->bind to receptor on renal proximal tubules-->coupled through cAMP to activate 1 alpha hydroxylase
--enzyme converts vitamin D to 1,25 DHCC (calcitriol)---lipid soluble hormone
--1,25 DHCC acts on duodenal epithelial cells
--intracellular receptor=Zn finger protein
--bind to response elements on enhancer regions of DNA to induce synthesis of Ca binding proteins which stimulate Ca2+ uptake from GI tract
--1,25 DHCC also causes Ca2+ reabsorption in the kidney
--1,25 DHCC mobilizes Ca2+ from the bone when PTH is present
BRINGS CALCIUM LEVELS BACK TO NORMAL
25 hydroxycholecalciferol: storage form of vitamin D
What is the action of calcitonin?
bind to receptors on osteoclasts and prevent demineralization
What is the action of bisphosphates?
treatment of osteoporosis
inhibit osteoclast action and resorption of bone
modest increase in bone mineral density (BMD), leading to strengthening of bone and decrease in fractures
Boniva (ibandronate), actonel (risedronate) and Fosamax (alendronate)
What are the symptoms and causes of vitamin D deficiency?
What are the symptoms and causes of vitamin A deficiency?
What are the symptoms and causes of vitamin E deficiency?
How is 1,25 Dihydroxycholecalciferol (calcitriol) synthesized?
*7 dehydrocholesterol derived from cholesterol in liver
*activation of 7-dehydrocholesterol by UV light in skin->cholecalciferol (vitamin D3)
--insufficient in people in cold, cloudy climates; vitamin D3 supplementation necessary
*25 hydroxylation in liver
--patients with severe liver disease may need to be given 25-DHCC or 1,25 DHCC
*1 alpha hydroxylation in the proximal renal tubule cells in response to PTH
--genetic deficiencies or patients with end stage renal disease develop renal osterodystrophy because of insufficiency of 1,25 DHCC --require 1,25 DHCC or drug analog not metabolized in kidney
patients includ: end stage renal disease secondary to diabetes mellitus; fanconi renal syndrome (renal proximal tubule defect), genetic deficiency of 1 alpha hydroxylase (vitamin D resistant rickets)
What is vitamin D toxicity?
results in hypercalcemia
unlike water soluble vitamins, vitamin D not excreted, instead stored in liver as 25, hydroxycholecalciferol
excess vitamin D promotes intestinal absorption of calcium and phosphate
large amount of vitamin D can contribute to osteoporosis
hypercalcemia can impair renal function
early signs: polyuria, poplydipsia, nocturia
prolonged hypercalcemia: calcium deposition in soft tissue, including kidney leading to irreversible kidney damage
Why do osteoporosis pateints take calcium and vitamin D?
take extra Calcium to be on high end of normal so parathyroid gland doesn't secrete PTH
--without PTH, osteoblasts increase Ca2+
What occurs in vitamin D deficiency?
--deformity of legs, muscle weakness
adult (after epiphyseal fusion): osteomalacia, less deformity, bone pain, muscle weakness
What is isotretinoin?
form of retinoic acid
used in treatment of acne
teratogenic: malformations of craniofacial, cardiac, thymic and CNS structures
contraindicated in pregnant women
What is the action of vitamin A?
maintenance of healthy epithelium and vision
What are the three vitamin A structures?
based on functional group on C-1
* retinol: hydroxyl
*retinoic acid: carboxyl
What is the action of retinol and retinoic acid?
required for growth, differentiation and maintenance of epithelial cells
bind to intracellular receptors (Zn-finger proteins) and regulate transcription through specific response elements
What is the action of vitamin A in vision?
retinal formed in trans form--not active
trans retinal converted to active cis-retinal in pigmented epithelial cells
cis-retinal transferred to opsin in rod cells and forms light receptor rhodopsin (functions similarly in rods and cones)
What are the steps of the vitamin A pathway in vision?
rhodopsin is 7 pass recpetor coupled to trimeric G protein transducin (Gt)
pathway activates cGMP phosphodiesterase, lowers cGMP in response to light
rhodopsin and transducin are embedded in disk membranes in outer rod segment
cGMP gated Na channels in cell membrane of outer rod segment reponse to decrease in cGMP by closing and hyperpolarizing membrane
rod cell is unusual becaus membrane is partially depolarized (-30 mV) at rest (in darkness) and hyperpolarizes on stimulation
How is vision signal sent to brain?
membrane is partially depolarized in dark so NT glutamate is continuously released
glutamate inhibits optic nerve bipolar cells --with which rods synapse
by hyperpolarizing the rod cell membrane, light stops release of glutamate, reducing inhibition of optic nerve bipolar cell and initiating signal to brain
What are causes and symptoms of vitamin A deficiency?
clinical manifestations don't arise until many months of extreme lack of dietary vitamin A because liver can store vitamin A
most common cause of blindness
3-5 years of age
most often due to fat malabsorption or liver cirrhosis
night blindness (rod cells responsible for vision in low light), metaplasia of corneal epithelium, xerothalmia (dry eyes), bronchitis, pneumonia, and follicular hyperkeratosis
Bitot spots on eyes
vitamin A important for immune cell differentiation so deficiency can cause frequent infection
What is the use of beta carotene?
found in yams, carrots, yellow squash and potatoes
cleaved to form retinal by intestinal enzymes
What is vitamin A toxicity?
excessive sweating, brittle nails and diarrhea
no beta carotene toxicity
Why is vitamin K important?
required to introduce Ca2_ binding sites of calcium dependent proteins
--gamma carboxylation of glutamyl residues on proteins introduces Ca2+ binding sites
*gamma glutamyl carboxylase requires vitamin K
*usually on glutamic acid
*k dependent carboxylation is cotranslation modifcation occuring as proteins are synthesized on ribosome in RER during translation
What proteins undergo vitamin K dependent carboxylation?
coagulation factors II (prothrombin), VII, IX and X
anticoagulation proteins C and S
What are the symptoms of vitamin K deficiency?
prolonged bleeding, easy bruising, potentially fatal hemorhhagic disease
What conditions predispose someone for a vitamin K deficiency?
fat malabsorption (bile duct occlusion)
prolonged treatment with broad spectrum antibiotics (eliminate intestinal bacteria that suply vitamin K)
breast fed newborns (little intestinal flora, breast milk very low in vitamin K), especially in home birht where postnatal injection of vitamin K may not have been given
infants whose mothers have been treated with certain anticonvulsants during pregnancy such as phenytoin (Dilantin)
What are signs of vitamin K deficiency?
poor nutrition and malnourishment, lack of medication, occult blood in stool, prolonged PT, normal LFTs
What is the difference between vitamin C and vitamin K deficiencies?
*platelets attracted by exposed collagen (increased bleeding time)
What are anticoagulants and how do they work?
warfarin and dicumarol
interfere with cotranslation modification during synthesis of precoagulation factors
anatgonize gamma carboxylation activity of vitamin K
**prevent coagulation in vivo not in vitro
**2-3 days to see full anticoagulant acitivity
herparin: short term anticoagulant activity; activator of antithrombin III
What is the function of vitamin E (alpha tocopherol)?
protects lipids from oxidative damage
prevents peroxidation of fatty acids in cell membrance, maintaining fluidity
What occurs in vitamin E deficiency?
hemolysis, neurologic problems, retinitis pigmentosa
What occurs in vitamin E toxicity?
hemorrhage in patients given warfarin
looks like vitamin K in excess
What are antioxidants?
1. catalase: destroys H2O2
2. vitamin C: water soluble, acts in cytoplasm
3. beta carotene: lipid soluble