Vitamins and Cofactors Flashcards
cofactors
small, non-protein molecules that associate closely with enzymes during enyzmatic reactions and are converted from one form to another in the reaction; metals (zinc, copper, iron, etc)
coenzymes
organic cofactors (mostly derived from vitamins)
vitamins
small, organic molecules necessary for cellular functions that cannot be synthesized by an organism
*precursors for co-enzymes
water-soluble vitamins
*B vitamins and vitamin C
-water soluble because they have lots of negative oxygen and nitrogen atoms to form hydrogen bonds with water
-most wash out in the urine (except B9 and B12, that are stored in the liver)
vitamin B1 name
thiamine
vitamin B1 (thiamine) - where is it found
yeast, legumes, pork, brown rice, whole grain cereals
-high temp (cooking) and high pH denatures
vitamin B1 - absorption
small intestine (esp. jejunum and ileum) via active transport and passive diffusion
vitamin B1 (thiamine) - organs with highest concentrations
heart and brain
vitamin B1 - half-life
10-20 days
vitamin B1 - populations at risk for deficiency
- absorption problems (small bowel resection, bariatric surgery, AIDS)
- storage problems/insufficiency (alcoholics, hyperemesis gravidarum, eating disorders)
vitamin B1 (thiamine)- biochemistry
*found in thiamine pyrophosphate (TPP); a cofactor for several dehydrogenase reactions, including:
-branched chain ketoacid dehydrogenase
-alpha ketogluturate dehydrogenase (TCA cycle)
-pyruvate dehydrogenase (links glycolysis to TCA cycle)
-transketolase (HMP shunt)
*vitamin B1 also has a role in the initiation of nerve impulse propagation independent of its coenzyme functions
vitamin B1 (thiamine) - deficiencies
*impaired glucose breakdown → ATP depletion worsened by glucose infusion (give thiamine before glucose)
*diagnosis made by increase in RBC transketolase activity following B1 administration
1. BeriBeri (wet or dry)
2. Wernicke-Korsakoff syndrome
Dry BeriBeri
*thiamine deficiency
*characterized by neurological complications:
-polyneuropathy
-symmetric muscle wasting
Wet BeriBeri
*thiamine (B1) deficiency
*characterized by neuronal complications PLUS high-output cardiac failure (due to systemic vasodilation):
-cardiomegaly and cardiomyopathy
-heart failure and peripheral edema
-tachycardia
-symmetrical peripheral neuropathy
Wernicke-Korsakoff syndrome
*results from thiamine (B1) deficiency
*a continuum
1. Wernicke enchephalopathy (most severe form)
-acute, life-threatening
-nystagmus, ophthalmoplegia, ataxia, confusion
2. Korsakoff syndrome (least severe form)
-chronic neurologic condition
-impaired short-term memory, confabulation
3. Wernicke-Korsakoff syndrome:
-damage to medial dorsal nucleus of thalamus, mamillary bodes
vitamin B1 (thiamine) - treatment for deficiency
IV thiamine, followed by oral supplements
vitamin B7 name
biotin
vitamin B7 - where is it found
yeast, liver, egg yolk, soybean products, enriched in flour foods
vitamin B7 (thiamine) - absorption
proximal small intestine and to a lesser extent the cecum
*gut bacteria also synthesize biotin as a byproduct of proteolytic actions
how do raw egg white disrupt a vitamin?
disrupt B7 (biotin) because AVIDIN binds to biotin and prevents its absorption
vitamin B7 - important organs
skin and nervous system
vitamin B7 - populations at risk for deficiency
*fairly uncommon because of how the gut bacteria produce biotin
*people who primarily rely on parenteral nutrition (bypassing the GI tract)
*people who drink raw egg whites
*absorption problems (small bowel resection, bariatric surgery, AIDS)
*storage problems/insufficiency (alcoholics, hyperemesis gravidarum, eating disorders)
vitamin B7 (biotin) - biochemistry
cofactor for many carboxylation rxns
*acetyl-CoA reductase
*proprionyl-CoA reductase
*pyruvate carboxylase
vitamin B7 - deficiency
*due to fatty acid synthesis disruption
-dermatitis (around eyes, nose, mouth)
-conjunctivitis
-mental status change/lethargy/hallucinations
-alopecia
-myalgias
-anorexia
-nausea
vitamin B7 - treatment of deficiency
-dietary changes
-oral supplementation
*not IV b/c we have endogenous supplementation via GI tract
vitamin B9 name
folate
folate vs. folic acid
folate = what is found in nature
folic acid = synthetic form
vitamin B9 (folate) - where is it found
foods like dark green leafy veggies, liver; cereals and grains are fortified with folic acid
*heat destroys folate in food
vitamin B9 - absorption
small intestine, esp jejunum, via carrier-mediated processes
*must be reduced to dihydrofolate and then to tetrahydrofolate to be biochemically active
vitamin B9 - important for?
DNA and RNA synthesis
-esp hematopoietic cells
-neuronal function
vitamin B9 - half-life
have some store but can deplete within weeks
vitamin B9 - populations at risk for deficiency
*absorption problems (small bowel resection, bariatric surgery, AIDS)
*storage problems/insufficiency (alcoholics, hyperemesis gravidarum, eating disorders)
*people who only eat canned foods (elderly, exclusive canned food diet)
*people with increased requirements (pregnancy and lactation: chronic hemolytic anemias; hemodialysis)
vitamin B9 - biochemistry
*must be reduced (using NADPH as a cofactor) to be active
*coenzyme for 1-carbon methylation
1. used for dUMP -> dTMP formation
2. used for conversion from homocysteine to methionine (deficiency = buildup of homocysteine)
vitamin B9 (folate) - peripheral blood signs of deficiency
*macrocytic (RBCs are larger), megaloblastic anemia
*pancytopenia (low counts of all cell types)
*hypersegmented neutrophils
vitamin B9 (folate) - treatment of deficiency
-increase dietary sources
-folic acid supplementation
vitamin B12 name
cobalamin
vitamin B12 - where is it found
meats, dairy products, eggs, clams; breakfast cereals are fortified
vitamin B12 (cobalamin) - absorption
1) need R protein in saliva and gastric juice to bind B12
2) need acidic environment in stomach to release B12 from foodstuff
3) need pancreatic proteases to release B12 from R protein and allow it to bind to IF
4) need intrinsic factor (IF) to bind B12 and facilitate absorption in the terminal ileum
5) need a terminal ileum
pernicious anemia
autoantibodies to gastric parietal cells cause no IF (intrinsic factor) production, so you can’t ABSORB B12
vitamin B12 (cobalamin) - populations at risk for deficiency
*people who eat primarily canned foods
*people on chronic proton pump inhibitors (need the acidic environment)
*people with pancreatic enzyme deficiency
*people with pernicious anemia
*people with functional or surgical absence of their terminal ileum
vitamin B12 (cobalamin) - biochemistry
*elevated serum homocysteine AND methylmalonic acid levels if B12 deficient
*cofactor for methyl transfer in homocysteine/methionine pathway
*cofactor to make succinyl CoA from methymalonyl-CoA, needed for TCA cycles and heme
vitamin B12 (cobalamin) - important functions
*DNA and RNA synthesis
-esp hematopoietic cells
-neuronal function
vitamin B12 - half-life
takes ~10 years to deplete stores
vitamin B12 - deficiency
*macrocytic, megaloblastic anemia
*pancytopenia
*hypersegmented neutrophils
vitamin B12 - presentation of deficiency
progressively worsening neurological finding
*symmetric paresthesias, numbness, gait problems (typically more in the legs)
*subacute combined degeneration of columns of spinal cord due to demyelination
*can progress to spasticity and paraplegia
*can be irreversible if not found and corrected
vitamin B12 - treatment of deficiency
depends on how severe the symptoms AND why they are deficient (do you need to bypass GI tract?)
*IM injections
*oral supplementation
B9 (folate) vs. B12 (cobalamin) deficiencies
-B9: elevated homocysteine, normal methylmalonic acid
-B12: elevated homocysteine AND elevated methylmalonic acid
vitamin C name
ascorbic acid
vitamin C - where is it found
foods such as citrus fruits, tomatoes, potatoes, brussel sprouts, cauliflower, broccoli, strawberries, cabbage, and spinach
*oxidative conditions destroy vitamin C in these foods (heat/light)
vitamin C - absorption
absorbed in the distal small intestine via active transport
vitamin C - important processes
*collagen synthesis (hydroxylation of proline and lysine)
*fatty acid transport
*neurotransmitter synthesis
*prostaglandin metabolism
*nitric oxide synthesis
*antioxidant
vitamin C - populations at risk for deficiency
*absorption problems (small bowel resection, bariatric surgery, AIDS)
*storage problems/insufficiency (alcoholics, hyperemesis gravidarum, eating disorders)
vitamin C (ascorbic acid)- biochemistry
*donates electrons to enzymes prolyl hydroxylase and lysyl hydroxylase to form hydroxyproline and hydroxylysine, which aid in COLLAGEN FORMATION
*reversible biologic reducing agent (electron donor for iron- and copper-containing enzymes)
*antioxidant
*cofactor for folate activation
*aids in fatty acid transport
vitamin C - deficiency
SCURVY
*swolllen / bleeding gums
*easy bruising, petechiae
*hemarthrosis
*anemia
*poor wound healing
*perifollicular and subperiosteal hemorrhages
*corkscrew hair
vitamin C - treatment of deficiency
*IV supplementation
*oral supplementation
