Environmental and nutritional disease Flashcards
Which mineral is needed for proper collagen cross-linking?
copper
Hydrolysis, reduction, oxidation are all in which phase of xenobiotic metabolism?
Phase 1
Glucuronidation, sulfation, methylation, and conjugation are in which phase of xenobiotic metabolism?
Phase 2
what is the most important catalyst of phase 1 reactions?
cytochrome p450
where in the hepatocyte are cytochrome p450 enzymes located?
ER
what are the two outcomes of p450 mediated metabolism of a xenobiotic?
detoxification or converstion into active compounds that cause injury
PPAR, CAR, and PXR are all examples of what?
nuclear receptors that bind to CYP
CYP bound to nuclear receptors then heterodimerize with which receptor to form the transcriptional activator?
RXR
how does CO cause toxicity? what are the clinical signs?
it has a 200 higher affinity for hemoglobin than oxygen does so it binds to hgb and RBCs can no longer carry oxygen, clinical signs include cherry red color of the skin and mucus membranes
what binds the majority of lead ingested?
teeth and bone - competes with calcium.
how does lead toxicity cause microcytosis and anemia?
lead has a high affinity for hemoglobin sulfhydryl groups - interferes with enzymes involved in heme synthesis which leads to impaired iron incorporation into heme
how does lead cause hemolytic anemia?
interferes with the ATPases in cell membranes
a peripheral demyelinating neuropathy can be seen with what toxicity?
lead
which two heavy metals bind to sulfhydrl groups?
lead and mercury
which form of mercury is in fish?
methyl mercury
via what mechanism does aspirin have anticoagulant effects?
blocks TXA2 and prevents platelet aggregation
nitrosylation of the RYR1 receptor is associated with which clinical syndrome? what about a mutation of RYR1?
rhabdomyolysis from heat stroke, malignant hypothermia
how is DNA damaged by ionizing radiation?
by ROS generated by radiolysis of water
which type of vitamins are more readily stored in the body, fat soluble or non-fat soluble?
fat soluble
Three major functions of vitamin A?
- regulation of cell growth and differentiation, 2. maintenance of vision, 3. regulation of lipid metabolism
carotinoids supply the majority of which vitamin?
Vitamin A
Which receptor in the liver is responsible for uptake of Vitamin A?
Apolipoprotein E
more than 90% of the bodies vitamin A is stored in which cell in the liver?
Ito cell
Cell surface receptors specific for RBP are important for cellular uptake of which vitamin?
Vitamin A
What is the difference between the vitamin A in meats vs. vegetables?
it is preformed in meat, and carotenes or pro-vitamin A form in vegetables
squamous metaplasia is seen with which vitamin deficiency?
Vitamin A
which vitamin A derivative has the higher affinity for RARs?
all trans retinoic acid
PPARs activated by retinoic acid, are key regulators of which processes?
lipid metabolism (fatty acid oxidation in fat, muscle, adipogenesis and lipoprotein metabolism)
which form of vitamin D is produced in the skin from exposure to UV light?
Vitamin D3
The liver converts vitamin D3 into which form?
25(OH)D = 25 hydroxycholecalciferol
The kidney converts 25(OH)D into which form?
1,25-dihydroxyvitamin D
which enyme is active in the conversion of vitamin D in the LIVER?
CYP27A1
Which enyme is active in the conversion of vitamin D in the KIDNEY?
1a-hydroxylase
where is the active form of vitamin D synthesized?
the kidney
which three mechanisms regulate the production of 1,25-dihydroxyvitamin D in the kidney?
PTH (stimulated by hypocalcemia), hypophosphatemia directly upregulates 1a-hydroxylase expression, negative feedback mechanism (increased levels of 1,25-dihydroxyvitamin D inhibit the 1a-hydroxylase enzyme
1, 25-dihydroxyvitamin D binds to the nuclear vitamin D receptor which associates with which other molecule?
RXR (like vitamin A and steroid hormones)
which protein is trascribed as a result of 1,25-dihydroxyvitamin D complexing with the nuclear receptor and RXR to increase calcium resorption in the GI tract?
TRPV6
Which protein is transcribed a a result of 1,25-dihydroxyvitamin Ds actions on the renal tubules?
TRPV5
how does vitamin D promote bone mineralization?
it stimulates osteoblasts to produce osteocalcin which is involved in the deposition of calcium during bone development
A decrease in which mineral from vitamin D deficiency impairs bone mineralization and leads to rickets?
phosphorous
Which step of collagen synthesis is vitamin C required for?
hydroxylation of procollagen
which vitamin is required for synthesis of neurotransmitters?
Vitamin C
Hemolytic anemia can be seen with which vitamin deficiency?
Vitamin E
bleeding diathesis can be seen with which vitamin deficiency?
Vitamin K
megaloblastic anemia is associated with deficiency of which vitamin?
Folate
Which suppress appetite - POMC/CART or NPY/AgRP?
POMC/CART suppress appetite
Leptin stimulates which neurons - POMC/CART or NPY/AgRP?
stimulates POMC/CART to suppress appetite
which adipokine is involved in thermogenesis?
Leptin
which adipokine stimulates fatty acid oxidation in skeletal muscle?
Adiponectin
what effect does adiponectin have on insulin sensitivity?
increases sensitivity to insulin
Adiponectin binding to its receptor activates cAMP dependent protein kinase A to inactivate which key enzyme required for fatty acid synthesis?
Coenzyme A carboxylase
which is the only known hormone that increases food intake?
Ghrelin
