Biochem (Vitamins) Flashcards
What are the main functions of vit D
Ca homeostasis
bone metabolism
Dec PTH
What is the metabolically active form of vita D
Calcitriol
Ercalcitriol
What kind of hormone is vit D
Steroid
Made from cholesterol, fat soluble
What inactive molecules preceed active vit D
Vit D2 (ergocalciferol) Vit D3 (cholecalciferol)
How do D2 and D3 from our diet become active?
Carried around by vit D binding proteins
Eat > get packaged in small int with bile salts into micelles > absorbed in enterocytes > incorporated into chylomicrons (lipoproteins) > lymph > blood > liver > hepatocyte ER
25-hydroxylase adds hydroxyl group to both molecules
D2 > ercalcidiol
D3 > calcifediol
Re-enter blood still bound to vit D binding protein
Liver > prox tubules of kidneys > renal cell mitochondria > 1 alpha hydroxylase adds hydroxyl group to both >
Ercalcitriol
Calcitriol
> active vitamin D
vit D3 synthesis from sun exposure
Sun exposure > 7 dehydrocholesterol, a precursor for cholecalciferol, absorbs UV B radiation > photolysis > pre vitamin D3 > cellular heat isomerizes pre vitamin D3 > vit D3 (cholecalciferol) > same path through liver and kidneys
Where is 7 dehydrocholesterol found
Keratinocytes in stratum spinosum and stratum basale
Low phosphate effects on vit D
Low phos > inc 1 a hydroxylase > active vit D transported to various tissues
Where are vit D receptors
Cytoplasm
Vit D role in nucleus
Stim transcription of genes and synthesis of protein
Vit D role in bones
Binds to vit D receptors on osteoblasts > release cytokines > RANKL + MCSF > fuse macrophage precursors together to form osteoclasts > break down bone > release Ca and phos into blood
Vit D role in enterocytes
Inc Ca and Phos absorption via stim synthesis of calbindin D 28 K (Ca binding protein)
Causes enterocytes to inc synthesis of sodium phos co-transporters > inc phos absorption
Vit D role in kidneys
Principal cells of DCT > stim synthesis of calbindin D28K > allowing more Ca reabsorp form urine
Tubular cells of PCT > causes inc synthesis of Na/Phos contransporters on apical surface > inc phos reabsorp
Where do we get vit D2
Plant sources in diet
Where do we get D3
Animal dietary or sun
What organs convert D2 and D3 to active vit D
Liver and kidney
Activation of vit D is triggered by:
PTH, when Ca/Phos levels are low
Effects of activated vit D
Stim bone resorption
Stim Ca/Phos reabsorption in small intestines and kidneys
PTH vs Vit D effects on Ca and Phos
PTH: inc Ca, dec Phos
Vit D: inc Ca, inc Phos
What are the fat soluble vitamins
Vit D
Vit E
Vit K
Vit A
What are the water soluble vitamins
B9 (folate) B7 (biotin) B6 (pyridoxine) B5 (pantothenic acid) B3 (niacin) B2 (riboflavin) B1 (thiamine) B12 (cobalamin) C
what is the first hydroxylation step of vit D conversion and where does it take place
liver
25-hydroxylase converts
vit D2/D3 > 25-hydroxyvitamin D (main storage form)
what is the second hydroxylation step of vit D conversion and where does it take place
kidneys
1-alpha hydroxylase converts
25-hydroxyvitamin D > 1,25-dihydroxyvitamin D (active)
causes of vit D deficiency
lack of dietary intake infants exclusively breastfed reduced sunlight exposure pigmented skin tones advanced liver disease CKD malabsorptive disorders (cystic fibrosis, celiac, chronic pancreatitis)
malabsorptive disorders effect absorption of what vitamins
fat soluble
A, D, E, K
vit D def sx
low 25 hydroxy vit D
low Ca, low Phos
hyper PTH (low ca over long time)
bone disorders associated with severe vit D deficiency
rickets
osteomalacia
high vitamin D sx
sx of hypercalcemia
excess vit D causes
granulomatous disorders
retinol common name
vit A
folate common name
B9
biotin common name
B7
pyridoxine common name
B6
pantothenic acid common name
B5
niacin common name
B3
riboflavin common name
B2
thiamine common name
B1
cobalamin common name
B12
vit A precursors/sources
beta-carotenes and retinol esthers (both from dietary sources)
retinol absorption, conversion, and storage
retinol absorebd in small intestine > converted into retinol esthers > picked up by chylomicrons > stored in liver stellate cells
retinol crosses cell membrane and enters nucleus in what form, to do what
retinoic acid > modify gene transcription
vit A main functions
orderly cellular differentiation and maturation
vision
vit A vision effects
retinol is part of rhodopsin (light sensitive protein important for photo transduction) >
sharpen vision and image
causes of vit A deficiency
lack of dietary vit A (rare) vit C deficiency pancreatic insufficiency (cant produce enzymes that break fat) intestinal malabsorption (IBD, bariatric surgery) cholestatic liver disease (bile is stuck in bile ducts; cant emulsify fat)
vit A def sx
impaired night vision/nyctalopia (impaired rhodopsin formation)
blindness in severe cases (metaplasia of cornea, corneal epithelium keratinizes - keratomalacia)
bidot spots in conjunctival epithelium - conjuntival squamous metaplasia - localized keratin debris
inc risk of pnemonia (due to squamous metaplasia)
squamous metaplasia of pancreatic exocrine ducts (esp due to def caused by CF)
growth disturbances
kidney stones
acute vit A toxicity sx
blurry vision
vertigo
N/V
chronic vit A toxicity sx
hepatic toxicity and enlargement cheilitis (lip inflammation) arthralgias alopecia hyperkeratosis (dry, thickened skin) pseudotumor cerebri (idiopathic intracranial hypertension ICH) > inc CSF pressure, papilledema)
vit A derviatives (s/a isotretinoin) contraindications
pregnancy
highly teratogenic
vit E exists in how many forms
8 tocopherols/tocotrionals
most biologically active form of vit E
alpha-tocopherol
vit E functions
cell membrane protection via neutralizing free radicals (antioxidant)
prevents oxidation of LDL
neuroprotection (may slow decline in alzheimers)
vit E deficiency causes
dietary intake (rare) fat malabsorption (pancreatic insufficiency, cholestatic liver dz, bariatric surgery) genetic: abetalipoproteinemia, AVED (ataxia w vit E def)
vit E def sx
hemolytic anemia (lack of ROS protection, RBCs pop/hemolyze) acanthocytes (spur cells) muscle weakness (skeletal myopathy) unsteadiness loss of coordiantion, ataxia slurred speech difficulty swallowing affects spinocerebellualr tracts loss of position/vibration sense loss of DTR infertility (males) low serum phospholipids similar to B12 sx
vit E toxicity sx
interferes with vit K metabolsim
inc bleeding with warfarin
inc risk of hemorrhagic stroke
necrotizing enterocolitis in infants
vit E high dose indications
age related macular degeneration
NAFLD
vit K natural forms
phylloquinone, menaquinone
vit K natural forms
phylloquinone, menaquinone
main source of vit K
leafy green veggies, gut flora
vit K activation
oxidized inactive vit K converted to reduced active vit K via VKOR (vit K epoxide reductase)
vit K is a cofactor for
gamma-glutamyl carboxylase (GGC), which catalyzes the post translational modification of the vit K dependent proteins: factors 2, 7, 9, 10, C, S
causes of vit K def
inadequate dietary intake fat malabsorptive disorders prolonged use of broad spectrum antibiotics (eradicate gut flora that produce vit K) warfarin newborns
what drug can mimic vit K def sx
warfarin; blocks VKOR which blocks vit K activation
reasons why newborns more likely to develop vit K deficiency
breastmilk low in vit K
dont have fully developed liver
no gut bacteria/sterile guts
doesnt cross placenta
vit K def sx
bleeding diathesis easy bleeding/brusining hematuria any bleeding intracranial bleeding (esp in newborn)
thiamine/B1 main functions
cellular metabolism
creating ATP
TTP cofactor for aerobic metabolism, BCAA catabolism, pentose phosphate pathway
TPP
thiamine pyrophosphate
TPP is a cofactor for which reactions
pyruvate dehydrogenase (links glycolysis and TCA cycle)
alpha ketoglutarate dehydrogenase (TCA cycle)
branched chain ketoacid dehydrogenase (BCAA catabolism)
transketolase rxn (PPP)
(transfers active aldehyde group)
B1/thiamine def causes
inadequate dietary intake (unenriched white rice; common)
alcoholics (reduces absorption)
B1/thiamine def progressions/sx
wet beriberi (dilated cardiomyopathy, high output HF, edema)
dry beriberi (pain, glove and stocking peripheral neuropathy, muscle weakness)
wernicke encephalopathy (confusion, ataxia, ophthalmoplegia w horizontal nystagmus)
chronic: korsakoff syndrome (irreversible memory loss, false memories confabulation, personality change)
areas of necrosis and hemorrhage in mammillary bodies, damage to ant and dorsomedial nuclei of thalamus (relay station of brain)
B2/riboflavin has important roles in
aerobic metabolism
making ATP
B2/riboflavin is a precursor for
mitochondrial electron carriers FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide)
B2/riboflavin absorption
first absorbed in prox small intestine > liver to be phosphorylated to make FMN (I) and FAD (II) for ETC
B2/riboflavin def causes
inadequate dietary intake (common) malnutrition chronic alcoholism liver disease malabsorption
B2/riboflavin sources
eggs, animal products, dairy, green leavy veg, enriched cereals