Disease Correlations Flashcards
Dyptheria
Dyptheria toxin puts a NAD+ onto eukaryotic elongation factor 2, eEF2 which inactivates protein elongation step in translation
Ricin poisoning
Ricin removes an A from the 28S rRNA of the large subunit and thus halts translation; is a poison derived from castor beans
Xeroderma pigmentosum
can’t repair DNA damaged by UV light damage (can’t fix pyrimidine dimers)
HNPCC
Hereditary nopolyposis colerectal cancer; autosomal dominant genetic condition that has mutations that impair mismatch repair
Treacher Collin’s Syndrome
gene mutation in genes that produce proteins involves in rRNA production (RNA polymerase I); leads to decrease rRNA production which can trigger apoptosis in cells relating to development of facial bones and tissues
alpha Amantin poisoning
found in “death cap” mushrooms; complexes with RNA poly II and inhibits the transcription of mRNA, causes liver failure, no antidote, just supportive care
Autosomal dominant retinitis pigmentosa
mutation in splicing factors that assemble U4, U5, and U6 snRPs, causes blindness in middle age
Why are patients given ethanol when they’ve ingested methanol
methanol is converted to formaldehyde via the enzyme alcohol dehydrogenase, ethanol competitively binds to a-d and gives the body time to get rid of the methanol through other pathways
Lysosomal storage diseases
Tay Sachs, insufficient HEXA enzyme that is a hydrolytic enzyme found in lysosomes that breaks down glycolipids; when broken, lipids (gangliosides –> sphingolipids) accumulate in the brain and cause disfunction ; red eyes
Gaucher’s: most common lysosomal storage disease; problems with enzyme glucocerebrosidase (glucoslyceramide accumulates) yellow sclera due to fatty deposits, heptomegly and spleenomegly sometimes neuro depending on type
Nieman Pick, and
Atherosclerosis
At high levels of LDL (low density serum lipoprotein) which is a carrier for cholesterol, LDL can deposit lipids./cholesterol on the artery walls which leads to thrombus formation
Statins inhibit the biosynthesis of cholesterol by inhibiting HMG-CoA reductase which is a key enzyme in the synthesis of cholesterol
Osteogenesis Imperfecta
Symptoms: blue sclera and brittle bones
Cause: substitution of glycine for bulkier amino acid causes disruption in triple alpha helix of collagen, steric hindrance causes bulge
Autosomal dominant, often diagnosed by bone breaks in utero
Alzheimer’s Disease
Symptoms: memory loss, dementia
Causes: problem with the folding mechanism for beta pleated sheets of amyloid proteins, get aggregation of misfolded sheets
Frutosuria
Essential: don’t have fructokinase enzyme, can’t turn fructose into fructose 1 phosphate, generally asymp. fructose not phosphorylated so can move in and out of cell, more fructose in blood
Fructose intolerance: don;t have enzyme aldolase B so can’t cleave F1P into G3P (eventually), keeps making more F1P and using all P that is needed to make ATP so have low ATP and can lead to liver failure in infants, need to cut fructose from diet
Sickle Cell Anemia
DNA single nucelotide mutation that causes a change in the protein translated, Glutamate to Valine, which causes hemeglobin aggregation/ protein clumping
Beri Beri
thiomen defficiency
The three enzyme complex of pyruvate dehydrogenase includes TPP (thiomine pyrophosphate, thiomine = vit B1), defficiency in thiomen causes problems in thiomine and arrests TCA cycle
Dry- muscle wasting, neurological problems
Wet- cardiac output increase, vasodilation, increase bv, edema
a ketogluterate dehydrogenase also uses thiomine in complex
Shoshin beri beri- fulminate cardiac failure
ID mutation
mutations of isocitrate dehydrogenase creates hydroxyglutamate which is thought to cause cancer
Gain a function mutation that makes isocitrate dehydrogenase an oncogene
mutation found in 80-90% of gliomas, research into inhibition of IDHs (IDH1,2,3)
Polygamist Downs
mutation in fumerase (enzyme that converts fumerate into malate) , found almost exclusively in FLDS, autosomal recessive, most children don’t survive infancy
Drug induced hemolytic anemia
Used to use a drug called Pamaquine to treat malaria, made from fava beans, uses up NADPH (sensed as a toxin and response is to transfer electrons to it but uses NADPH–> NADP+); this causes problems for people with a G6 phosphate dehydrogenase deficiency which is not uncommon among africans and africans americans because it means you make less NADPH and malaria needs NADPH to survive
Most common disease related enzyme variant
Can also see problems with vit K, aspirin, and cipro precursor
Lactic acidosis
lactic acid build up due to overuse of the pyruvate to lactate pathway
Galactosemia
Lactose cleaves to galactose and glucose, galactose turns into GAL1P via galatokinase and then to glucose 1 phosphate via a transferase and finally to G6P; in galactosemia, the transferase is mutated to GAL 1P builds up in cells and causes liver damage, mental retardation and vision problems
Pellagra
Disease from lack of NAD+ and therefore lack of ATP synthesis via anerobic glycolysis /TCA–> can get NAD+ from diet or synthesized from Tryptophan, need niacin (B3) to synthesize as well, without you can’t make NAD+ and run TCA cycle ( IC to AK; AK to SCA; M to OAA, Pyr to ACoA, G3P to 13BPG) ; dermatitis, diarhea, dementia and death, can ameleiorate in corn eating pops by adding lime juice to corn
Mitochondrial respiratory chain diseases
issue with mitochondrial (mtDNA) DNA, constellation of symptoms but generally seen with lactic acidosis (not enough ATP made, increase glycolysis); ragged red fibers; sideroblastic anemia; and LHON Leben’s hereditary optic neuropathy –> blindness
mitochondria function decreases as one ages which may have an effect on insulin resistence
Biotin Deficiency
swollen tongue, loss of appetite; can get it from eating a lot (a lot ) of egg whites bc avidin in egg whites binds to biotin and prevents CO2 from binding; more common in cats than in humans, means you can’t run the Pyr –> PEP step of gluconeogenesis and can’t remake glucose
Dinitrophenol
electron transport chain decoupler that acts by poking holes in the mitochondrial membrane so you can’t build a H+ gradient and power the complex V ATP synthase pump; used in a diet pill that caused death from hyperthermia because instead of making ATP, you generate heat (function of brown fat)
UCP1 is a protein that makes mitochondria leaky (increased levels in people with more brown fat)
