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)
Van Gierke’s disease
glucose 6 phosphotase doesn’t work so you can’t break down glycogen, causes hypoglycemia and enlarged liver, and lactic acidosis
McArdle’s syndrome
issue with myophosphorylase which breaks down glycogen in muscles, get muscle cramps in absence of lactic acid build up (because not breaking down glucose); relatively benign
Cori Disease
Issue with debranching enzymes like a 16 glucotransferase and a 16 glucosidase which cause a fasting hypoglycemia
Glycogen storage disease ( same subheading as McArdle’s and von Gierke’s )
Anderson’s Disease
problem with branching enzyme means that can only make very long unbranched glycogen enzymes that are then stored in the liver; these have low solubility so precipitate in liver and other parts of the body including the heart, death by five
Congenital hyperammonemia
genetic deficiencies in one of the five enzymes in the urea cycle (leads to hyperammonemia that has a direct neurotoxic effect on the CNS)
common ones include:
- ornithine transcarbamoylase deficiency (can’t make citrulline) - failure to make urea leads to hyperammonimia in first weeks after birth
- arginase deficiency ( can’t turn arginine into l orinthine and release urea); less severe because arginine has the two waste nitrogens incorporated into it and can be excreted in the urine
Acquired hyperammonemia
liver disease like cirrhosis can result in the formation of collateral circulation around the liver so that portal blood bypasses the liver and ammonia can’t be filtered out
Maple Syrup urine disease
deficiency in branched chain a keto acid dehydrogenase (leucine, isoleucine, and valine) BCKD which elevates the concentration of branched chain amino acids in plasma and urine, leads to cerebral edema and neurological problems, treatment involved restricting dietary intake of BCAA
Phenylketonuria
PKU; deficiency in phenylalanine hydroxylase, hyperphenylalanemia and a deficiency in tyrosine (made by phenylalanine) ; severe nervous system symptoms; hypopigmentation (need tyrosine to make melanin) ;
Homocysteine
causes oxidative damage inflammation and endothelial damage leads to increased heart and stroke problems; B6, B12 and folate found to lower homocysteine levels but not an effect on heart outcomes
Spina Bifida
too little THF (B9) in mothers leads to neural tube defects in fetuses
Orotic aciduria
issues with the enzymes (one or both) that catalyze the conversion of orotate to orodylate and orodylate to uridylate (UMP), this causes poor growth; megoblastic anemia; and large amts of orotate in urine
helped by adding in uridine (and cytidine)
Fluoruracil
flurodeoxyuridylate binds irreversibly to thymidylate synthase so can’t make T so can’t make DNA and cells can’t divide
( N5N10 methyl THF –> dihydroxyfolate via thymidylate synthase and converted dUMP to dTMP)
suicide inhibitor
aminoplerin and methohexate
cancer drug that inhibits dihydroxyfolate reductase which is recycling methyl donor N5N10 methyl tetrahydrofolate so if you can’t recycle you also can’t make TMP and cell can’t divide
Lesch Nyan Syndrome
loss of HGPRT (hypoxanthine guanine phosphobusyl tranferase)
hypoxanthine is the base of IMP (inocinate monophosphate) which is the first purine made in the purine synthesis pathway; also used to turn guanine into GMP
leads to excessive uric acid, high PRPP, and low IMP and GMP (
Gout
uric acid crystals in joint leading to inflammatory response either due to overproduction of uric acid (mutation in PRPP synthase so you get more PRPP, more purines, and more uric acid) or, more often, underexcretion (90%)
treat by giving allopurinol which inhibits xanthine oxidase (converts hypoxantine to xanthine and xanthine to uric acid) and leaves you with more hypoxanthine which is more soluble than uric acid
Burkitt’s lymphoma
error in recombination in immune cells (B and T cells) impair ability to create antibodies; in Africa associated with Epstein Barr virus and usually in face/mouth as opposed to non-African/spontaneous which is not usually associated with EBV; malaria erodes viral resistance
Lupus
make antibodies to splicing snRPS
Beta thalassemia
Abberent splicing produces non functional or no beta globins leading to a build up of alpha globins
hyperamminemia
too much ammonia in blood due to mutation in urea cycle enzymes like ornithine transcarbamylase or arginosuccinase
brain swelling thought to be due to the conversion of glutamate to glutamine via glutamine synthase
treat arginonsuccinase def by adding extra arginine because once you get arginosuccinate concentrations high enough you can secrete it
orotic aciduria
issue with enzyme that converts orotate and PRPP to orydylate; end up with a build up of orotate that gets excreted treat with uridine and cytidine bc can make other riboses via salvage pathways
Diabetes
Symptoms: polyuria, polydypsia, polyphagia; high blood glucose; ketosis (diabetic ketoacidosis from increased fat lypolysis) weight loss;
Type 1: not enough insulin produced (in untreated type 1 major source of fuel = fats)
Type II: resistance to insulin
