Vitamins and Minerals Flashcards
what enzymes does thiamine assist with?
- pyruvate dehydrogenase
- alpha ketoglutarate dehydrogenase (TCA)
- transketolase (HMP shunt)
- branched chain ketoacid dehydrogenase (metabolism of valine, leucine, isoleucine)
what is riboflavin involved with? (B2, FAD)
dehydrogenases, redox reactions
what reactions does niacin assist with? (NAD)
dehydrogenase
what does panthothenic acid/coenzyme A (B5)
- fatty acid synthase
- pyruvate dehydrogenase
- alpha ketoglutarate dehydrogenase
what reactions does pyridoxine phosphate help with? (PLP, B6)
- aminotransferase
2. ALA synthase
what reactions does biotin assist with?
- pyruvate carboxylase
- acetyl coa carboxylase
- propionyl CoA carboxylase
what reactions does folic acid assist with
- thymidylate synthase
2. purine synthesis enzymes
what does B12 assist with
- homocysteine methyltransferase
2. methyl-malonyl CoA synthase
what does ascorbic acid Vitamin C assist with
- prolyl and lysyl hydroxylase
2. dopamine b-hydroxylase
what causes dry beriberi?
moderate thiamine deficiency, peripheral neuropathy, muscle weakness, fatigue, short attention span
what causes wet beriberi?
severe thiamine deficiency, high output cardiac failure, edema
effects of diminished thiamine?
energy metabolism is affected, causing a drop in ATP levels. neurons are affected by this drop first, causing the neuropathy.
what generally causes beriberi??
any inflammation in the intestine that causes decreased absorption of vitamins, especially in chronic alcoholics
why are chronic alcoholics more susceptible to thiamine deficiency?
- alcohol inhibits the absorption of thiamine
2. excretion of thiamine is increased
explain the symptoms of thiamine deficiency?
activity of PDH and alpha ketoglutarate dehydrogenase is important for energy metabolism, esp nervous cells. decrease in ATP results in weakness and amnesia.
what causes Wernicke-Karsokoff syndrome
combination of thiamine deficiency and alcohol toxicity
characteristics of Wernicke-Karsokoff syndrome
- decreased gait function
- decrease in memory and clear thinking
- psychosis/mental derangement/delerium
- ataxia
- paralysis of eye muscles
- confusion/hallucination/disorientation/frenzy
how is Wernicke-Karsokoff treated?
thiamine injections!
how to test for thiamine deficiency?
transketolase
what is riboflavin a precursor for?
FAD and FMN
when is riboflavin reduced?
- poor diet
2. infant receiving phototherapy for neonatal jaundice (is degraded by UV light, give pt riboflavin supplement)
what can riboflavin deficiency cause?
corneal neovascularization, cheilosis, glottitits, stomatitis, magenta colored tongue, light sensitivity
what is niacin a precursor for?
NAD, NADPH
how is niacin taken into the gut?
dietary coenzymes are hydrolyzed in GI and free nicotonic acid and nicotinamide are absorbed in small intestine, found in whole grains, milk and meat
when is a deficiency in niacin found
corn based diet, called Pellagra
what are the signs of a severe niacin deficiency? 4D
- dermatitis
- diarrhea
- dementia
- death
how does niacin treat hypercholesterolemia
- inhibits lipolysis in adipose (inhibits hormone sensitive lipase)
- inhibits esterification of TG in liver
- reduces VLDL synthesis in liver (d/t decreased FFA release) and therefore a decrease in LDL
- increases lipoprotein lipase activity
side effects of niacin treatment
- flushing
- itching
- GI distress
- hyperglycemia
- hyperuricemia
- hepatotoxicity
what is panthothenic acid a precursor for?
coenzyme A, makes molecules reactive
what does coenzyme A do?
functions in the transfer of acyl groups, the thiol group carries acyl groups as activated thiol esters
is panthothenic acid deficiency seen in humans
rarely, bc is lethal so they would already be dead
what enzymes is B6 a cofactor for>
- transamination (AST, ALT)
- decarboxylation (dopa decarboxylase, histidine decarboxylase, glutamate decarboxylase)
- condensations (ALAS)
- cystathione synthase, lyase
what does glutamade decarboxylase do?
converts glutamate to GABA
what is seen in B6 deficiency?
peripheral neuropathy, weakness, fatigue (decreased ALAS, heme synthesis), irritability, stomatitis, glossitis, psychiatric symptoms, epileptic seizures (d/t decreased GABA), sideroblastic anemia (microcytic, hypochromic anemia)
what could be the difference between microcytic hypochromic anemia in B6 deficiency versus iron deficiency
B6 would see spikes on RBC and no change in iron levels in the serum, iron deficiency would see decreased iron
what is unique about B6 as a water soluble vitamin?
is toxic in high doses, leading to peripheral sensory neuropathy, nerve damage causing weakness, loss of sensation
what enzymes is biotin helpful in?
ABC enzymes
- pyruvate carboxylase (pyruvate to OAA)
- acetyl coa carboxylase (acetyl coa to malonyl coa)
- propionyl coa carboxylase (propionyl coa to methylmalonyl coa)
what is the problem with drinking only raw egg whites
the protein avidin binds biotin tightly, leading to a decrease in biotin absorption
symptoms of biotin deficiency?
dermatitis, alopecia, glossitis, loss of appetite, nausea
what more commonly causes biotin deficiency?
deficiency in biotinidase, which cleaves biotin-lysine conjugation biocytin to be available for uptake, nondietary biotin deficiency
what causes megaloblastic anemia?
folic acid deficiency
b12 deficiency due to methyl-folate trap
how is the active form of tetrahydrofolate synthesized?
dihydrofolate reductase in the intestine
how do sulfonamides work
inhibit synthesis of pteroic acid in bacteria that inhibits FH4 formation, thus inhibiting bacterial growth
what is the action of trimethoprim
inhibits bacterial dihydrofolate reductase
what causes B12 deficiency?
malabsorption (not enough enzymes to cleave R-binding protein)
what is seen in B12 deficiency?
neurological dysfunction with demyelination because SAM is required for choline synthesis (phosphatidyl choline)
what is a deficiency of vitamin C?
scurvy
how does ascorbic acid work?
is a reducing agent and scavenger of free radicals, and is needed for maintenance of normal connective tissue and wound healing, and facilitation of iron absorption in the intestine to keep metals in their reduced state
explain the processes that vitamin C assists with?
- hydroxylation of prolyl and lysyl residues in procollagen to collagen
- carnitine synthesis (requires 2 Fe2+ containing, vit C dependent oxygenases)
- norepinephrine and serotonin synthesis requires dopamine beta hydroxylase (vit C dependent copper)
- 7 alpha hydroxylase for bile acid synthesis
symptoms of scurvy
- dry mouth and eyes
- decaying and peeling gums
- loose teeth
- delayed wound healing
- eccymosis/petechia
- weakness and lethargy
due to deficiency of hydroxylation of collagen (defective CT)
what vitamins are associated with decreased incidence of chronic diseases?
diets rich in antioxidants (vit C is used to regenerate vit E, controls lipid radicals) like vitamin A, C, E associated with decreased incidence of some chronic diseases liek coronary heart diseases and cancers
function of Vit D
works in response to hypocalcemia, normal serum calcium levels
deficiency in vitamin D
rickets in childhood, osteomalacia in adults
function of vitamin A
retinoic acid, retinol act as growth regulators in epithelium, retinal in rod and cone cells
deficiency of vitamin A
night blindness (due to decreased retinal and rhodopsin), light sensitivity, metaplasia of corneal epithelium, dry eyes, bronchitis, pneumonia, follicular hyperkeratosis
function of vitamin K
carboxylation of glutamic acid residues in Ca binding proteins, coagulation factors II, VII, IX, X, proteins C and S
deficiency of vitamin K
easy bruising or bleeding, increased PTT
what is vitamin K deficiency associated with?
fat malabsorption, long term antibiotic therapy, breast fed newborns, infants of mothers that took anticonvulsants during pregnancy
function of vitamin E
antioxidant in lipid phase, protects membrane lipids from peroxidation and helps prevent oxidation of LDL particles
deficiency of vitamin E
hemolysis, neurologic problems, retinitis pigmentosa
3 forms of vitamin A
- retinol
- retinal
- retinoic acid
parent compound of vitamin A
retinol
how can retinal and retinoic acid be produced other than vitamin A?
beta carotene, because it is cleaved in the intestine to yield 2 molecules of retinal
what form of retinal is essential for vision
11-cis retinal, is a major component of rhodopsin in the rod cells
describe when the retina is exposed to light
- light absorbed by rhodopsin
- 11-cis retinal is isomerized to 11-trans retinal
- this isomerization activates rhodopsin, GPCR
- activated rhodopsin activates transducin through the association of GTP
- GTP bound transducin activates phosphodiesterase,
- activated phosphodiesterase hydrolyzes cGMP, decreases cGMP
- decreased cGMP closes Na channels causing hyperpolarization of membranes
- hyperpolarization inhibits rate of glutamate release
- decreased glutamate release signals brain through optic nerve
what happens in the dark?
- phosphodiesterase is not activated, increases cGMP
- Na channels stay open
- glutamate still released
- no signal to optic nerve
- eye can detect a single photon
how is retinoic acid a gene regulator?
- regulates expression of genes that affect growth, development, differentiation of tissues, maint. of epithelial cells, early development of embryo
how does retinoic acid bind to receptors and affect growth
???
- travels directly to nucleus to retinoic acid receptors and retinoid X receptors
- retinoid X receptors bind and form dimers with vitamin D receptor or thyroid receptors
- promotes differentiation of epithelial cells and mucus secretion from columnar epithelial cells
what occurs in a deficiency of retinal?
night blindness, prolonged deficiency leading to irreversible loss of visual cells
what occurs in retinoic acid deficiency?
impairs function of vitamin D and thyroid hormones so leads to a decrease in growth rate in children as bone development is slowed, can affect spermatogenesis in males
specific effect on the eye of retinoic acid deficiency?
metaplasia of corneal epithelium (columnar epithelium converted to keratinzed sequamous epithelium), xerophthalmia, pathologic dryness of conjunctiva and cornea bc eye loses its mucus secreting cells and becomes keratinized.
how is retinoic acid used in dermatology?
acne, psoriasis and skin aging treated with topical application. severe recalcitrant cystic acne treated with oral administration of 11-cis retinoic acid
what is the most potent vitamin E
alpha tocopherol
what may lead to vitamin E deficiency
fat malabsorption
how does vitamin E deficiency lead to hemolytic anemia?
increase in free radicals damages RBC membranes
what is the active form of vitamin K and how is it made
K2 (menaquinones) is active form, is made from the cleavage of K1 by bacteria of intestinal flora
what is the dietary form of vitamin K?
phytomenadione, found in green leafy vegetables, is cleaved to be K2
why is vitamin K required for blood clotting
vitamin K is the coenzyme for glutamate carboxylase, which catalyzes the y-carboxylation of glutamate residues of coag factors II, VII, IX, X and proteins C and S during synthesis in hepatocytes
what does the carboxylation of glutamate residues do?
creates calcium binding sites in blood clotting factors II, VII, IX, X. vit K conezyme for glutamine carboxylase to y carboxylase
what occurs if there is no vitamin K to help with glutamate carboxylase?
glutamate residues cannot be y-carboxylated to make calcium binding site for clotting factors II, VII, IX, X
what is the first vitamin to be deficient in fat malabsorption?
vitamin K is not stored, so with acute fat malabsorption, it is the first fat soluble vitamin to be deficient
in what people is vitamin K deficiency common?
newborns! because they don’t have gut flora to cleave K1 to K2. called hemorrhagic disease of the newborn
how would a patient present with a deficiency in vitamin K?
presents with hemorrhagic conditions, due to decreased gamma carboxylation of cofactors. aka not functional coaguation pathway
function of warfarin and dicumarol
inhibits conversion of K1 to K2, therefore antagonizing gamma carboxylation of glutamate by vitamin K
what can zinc deficiency lead to
hair loss, dermatitis, poor wound healing, depressed immune function
what does copper do
cofactor for oxidases that transfer electrons to oxygen like dopamine beta hydroxylase, cytochrome c oxidase, superoxide dismutase, tyrosinase, and monoamine oxidase.
what is menkes syndrome
rare, X linked recessive disease, deficiency of ATP dependent membrane transporter for Cu, Cu cannot be absorbed by intestinal cells and are excreted in the urine. leads to copper deficiency
characteristic of menkes syndrome?
microcytic hypochromic anemia, hemorrhagic vascular changes, bone demineralization, neurological problems
what is wilsons disease
autosomal recessive mutation in kidney copper transporter. cannot excrete copper in urine, so accumulates in blood. excessive of copper in brain, liver, kidneys.
characteristic of wilsons disease?
liver damage, neurological and hematological complications
