jdlevenson's version from 2015-06-17 23:25


Question Answer
VEGF needed forangiogenesis
JAK2 is a cytoplasmic TYR Kinase so that meansit is a kinase that is a/w a receptor that does not have intrinsic kinase activity; TYR receptor (like EPO) needs an associated cytoplasmic kinase like JAK2 to initiate downstream signaling
JAK2 mutations inPV, ET, PMF
PV symptomsHeadache, weakness, diaphoresis, aquagenic pruritus, facial plethora, splenomegaly
PV labsLow EPO and high erythrocyte mass, thrombocytosis and leukocytosis
PI3K/ AKT/ MTOR pathway is intracellular signaling pathway important forAnti-apoptosis, cellular proliferation and angiogenesis; GF -> PI3k -> PIP2 to PIP3 -> AKT activation, a SER/THR protein kinase -> mTOR activated
mTOR inhibited byPTEN, tumor suppressor that removes P from PIP3
What drug targets mTOR pathwaySirolimus/ rapamycin
JAK activatesSTAT which goes to nucleus
Blue black pigment in ears, nose and cheeks?Onchronosis; retained homogentisic acid (due to deficiency in homogentisic oxidase causing alkaptonuria) leads to build up and deposition in muscles, tendons, and cartilage.
Defiency of homogentisic oxidase leads to prevention of Tyrosine -> ?Fumarate.
Alkaptonuria symptoms?Relatively benign AR disorder; just onchronosis; pees turns black if allowed to stand and then become oxidized.
Cysteine synthesized fromSerine and homocysteine (which is from methionine)
Leucine -> ? vs Valine and Isoleucine -> ?Leucine -> Acetoacetate and acetone; Valine and Isoleucine -> Succinyl coA.
What happens if pyrimidine dimers from UV rays aren’t repairedDNA mutations
Pyrimidine dimers are removed viaNucleotide excision repair via specific endonuclease complex; detects abnormalities in the DNA structure caused by the formation of DNA photoproducts; it will nick the damaged strand on both sides of the dimer and defective region is excised. DNA polymerase synthesizes new DNA in the place of damaged DNA and DNA ligase seals the remaining nick.
Xeroderma pigmentosum is defect inNucleotide excision repair; severe photosensitivity and development of skin cancers at young age
UV vs ionizing radiationUV -> pyrimidine dimers; ionizing radiation -> double strand DNA breaks (fractured ends may be joined by nonhomologous end joining)
DNA mismatch repair works viaHypermethylation of parent strand to help idenfiy non-mutated strand for use as a template (?)
Chemical exposure ->Deamination of DNA bases (C -> U; A -> hypoxanthine), which may also occur spontaneously; corrected by BASE EXCISION repair that uses specific glycosylases* without disruption of phosphodiester backbone. Then apurinic or apyrimidinic residues are removed by specific endonucleases and replaced with correct base via DNA polymerase.
Fatty acid oxidation produces more ATP but...Requires more O2 consumption that glycolysis or glucose oxidation.
Main source of energy production in cellsFatty acid oxidation. 60% of energy production.
Fatty acid oxidation inhibitors may benefitAngina patients because then less 02 would be used; more oxygen efficient and potentially beneficial.
Vitamin C overdoseFalse negative stool guaiacs; diarrhea; abdominal bloating; calcium oxalate nephrolithiasis
Vitamin E overdoseHemorrhagic stroke (in adults) and necrotizing enterocolitis (infants)
N-acetylglutamate is essential forActivating Carbomyl Phosphate Synthase I. Formed from Acetyl CoA and Glutamate in N-Acetylglut Synthetase.
Vitamine E deficiency leads toNeuromuscular disease (skeletal myopathy, spinocerebellar ataxia, pigmented retinopathy) and hemolytic anemia. Vitamin E protects cells from oxidation; long neurons and erythrocytes are two most susceptible to oxidation. After axonal degeneration develops, CNS symptoms appear too, such as DC, spinocerebellar, and peripheral nerves.
Vitamin E deficiency symptoms mimicFriedreich ataxia – ataxia, dysarthria, loss of position and vibration sensation.
Anytime you have fat malabsorption or abetalliporpoteinemia- like in CF – need to thinkADEK deficiencies.
Acetylated histones generallyBind less tightly to DNA to allow transcription.
B12 deficiency, what does accumulated methylmalonic acid doMyelin synthesis abnormalities -> damage including subacute, combined degeneration of posterior and lateral spinal columns and sometimes axonal degeneration of peripheral nerves too. Loss of position and vibration sensation, ataxia. SO BOTH MOTOR AND SENSORY
tRNA adds AA at 3 or 5 prime end3 prime.
Urea cycle disorder treatmentsProtein restriction/ balancing protein intake and output. Body should receive only amino acids necessary for growth and development but not in excess such that excessive ammonia is formed.
THB/ B4 is used in making what neurotransmittersTYR and DOPA (on Phe pathway) and Seronin (via tryptophan pathway) and Nitric oxide.
Glycine is an inhibitory neurotransmitter with primary action inSpinal cord.
Methionine is precursor in synthesis ofCysteine, carnitine, taurine, lecithin.
Which DNA polymerase has 5 to 3 exonuclease activityDNA poly I, which is responsible for removing RNA primer and for exonuclease excision and repair (whereas ENDOnuclease is responsible for nucleotide excision repair during G1)
Deficiency of Folate develops within3-4 months
Deficiency of B12 develops over3-4 years. Previously well nourished individuals have hepatic B12 reserves sufficient to last for up to several years.
Cells that do not have sorbitol dehydrogenaseSchwann cells, Retina, Kidneys (this does not include lens, which does have SDH but just small amounts that can be overwhelmed)
PCR does NOT require the sequence of the target DNA to be known but it does needFlanking sequences of the DNA in order to make the primers
PCR requiresDNA template, 2 primers, DNA polymerase (Taq) and Deoxynuceotide triphosphates. Remember, only makes DNA, not protein products.
Debranching enzyme deficiency can be differentiated from others byAccumulation of abnormally short outer dextrin like structures in the cytosol of hepatocytes with an absence of histopathological fatty infiltration of liver. Affects liver and muscle but may present with only liver involvement.
Cori disease findingsHypoglycemia, hyperTG, ketoacidosis and hepatosplenomegaly BUT ALSO small chain dextrin like accumulation within cytosol of hepatocytes.
Pompe disease has cardiomegaly ANDGeneralized hypotonia.
Von Gierke disease clinicalSevere fasting hypoglycemia, high TG, high blood lactate, Hepatic Steatosis*, high uric acid
McArdle Disease lab/ microscope findingHigh glycogen in muscle and low blood lactate
Alpha thalassemia is common in people ofSoutheast Asian descent
Beta thalassemia minor is common in people ofMediterranean heritage
TARGET CellsHALT – H HbC, Asplenia, Liver diseae and Thalassemias
Bacterial mRNA unlike DNA can bePolycistronic. One mRNA for multiple proteins. Example Lac Operon in E. Coli.
Xeroderma pigmentosum is caused byUV-specific endonuclease activity
Proofreading of DNA polymerase is done by3’ to 5’ EXOnuclease activity.
Defective exonuclease activity/ mismatch repair is a/wHNPCC/ Lynch Syndorme.
Causes of lactic acidosisEnhanced metabolic rate (seizures, exercise), Reduced oxygen delivery* (cardiac or pulm failure, shock, tissue infarction), Diminish lactate catabolism due to hepatic failure or hypoperfusion, Decreased oxygen utilization (CN poisoning), Enzymatic defects in glycogenolysis or gluconeogenesis
Poor bicarbonate reabsorptionMM and Drug tox (acetazolamide) and other
Breast milk is insufficient of what two hormones for newbornVitamin D and K. K is given parenterally (IM at birth) to prevent hemorrhagic disease of newborn.
Exclusively breastfed infants should receiveVitamin D supplementation.
B6 forTransamination and decarboxylation of AA, gluconeogenesis and other.
Nonoxidative reversible portion of HMP shunt usesTransketolase and transaldolase. Some cells do not use the oxidative phase reactions to produce cytosolic NADPH but all cells synthesize ribose from F-6-P using nonoxidative reactions.
Vitamin A is effective as treatment inMeasles.
HMP shunt occurs inCytoplasm
Spliceosomes splice as 5’ end of intron and join it toEnd of branch point.
Anti-snRNP antibodies are present inMixed connective tissue disease.
Sideroblastic anemia fromDecreased ALA synthase due to B6 deficiency or Lead poisoning causing build up of precursors.
Heme biosynthesis occurs inMitochondria and cytoplasm. Heme part is in mitochondria.
Vitamin C is involved in what part of collagen synthesisHydroxylation of proline -> Hydroxyproline. Lysine also must be hydroxylated.
Hydrogen and disulfide bonds make up triple helix for collagen. When there are problemsOsteogenesis Imperfecta.
Ehlers Danlos caused byMutations affecting genes or enzymes such as lysyl hydroxylase or procollagen peptidase, both occurring outside cell*. Leads to MORE SOLUBLE collagen.
Triple helix formation happens in nucleus and is formed fromInterchain, not intrachain, disulfide bonds form at the C-terminus between 3 pro-alpha chains aligning the helical domains into a conformation favorable for triple helix.
Aberrant serine and threonine residue phosphorylation by serine kinaseleads to insulin resistance.
What can phosphorylate serine and threonine to cause insulin resistanceTNF-alpha, catecholamines, glucocorticoids, glucagon.
PPAR gamma leads toImproved insulin sensitivity.
Thiazolidinediones/ TZD work howPPAR gamma activation -> decrease blood sugar.
Nitrites poison howOxidize heme iron to ferric state. Ferric, 3+, cannot bind oxygen and becomes methemoglobin.
Methemoglobin causes shiftLeft. Increased affinity.
Nonpolar, hydrophobic amino acids form what part of G-protein coupled membrane-bound receptorsTransmembrane. NP HP – Phe, Ala, Met, Iso, Val.
Iron containing proteins includeHemoglobin, Myoglobin, Cytochrome Oxidase. Heme is Protoporphyrin and Iron.
Which cells cannot use ketonesErythrocytes/ RBCs since they do not have mitochondria and also hepatocytes
One of rare reactions to occur in outer mito membrane FATTY ACYL SYNTHETASE
DHB Reductase deficiency and then DHB reductase leads toReduction in TYR, DOPA, 5HT, NO (5HT and NO via different pathways). Less Dopa and Dopamine -> Less inhibition of Prolactin release -> Increased levels of Prolactin
Sideroblastic Anemia causesPb (from lead paint, batteries, etc) and B6 deficiency (INH)
Porphyria Cutanea Tarda is exacerbated by ? vs Acute intermittent Porphyria is exacerbated by?P. Cutanea Tarda -> Alcohol. Acute Intermittent porphyria -> Barbitruates or other benzo inducers.
Acute intermittent porphyria is geneticallyautosomal dominant -> late onset, episodic, variable expression
What increases risk of brown pigment stonesE. Coli, Ascaris and Liver Fluke Opisthorchis Sinensis. Ascaris – common roundworm that infects 25% of world’s population especially in
C. Sinenesis increases risk ofGallstones, cholangitis, cholangiocarcinoma.
What stimulates PKCDAG vs. IP3 increases intracellular Ca to further activate PKA
Subperiosteal hematomasVitamin C deficiency.
Vitamin C what type of reactionsHydroxylation. Ex. Activation of prolyl and lysyl hydroxylase precursors which are necessary for hydroxylation of procollagen
ApoA-1LCAT activation/ cholesterol esterification
ApoB48Chylomicron assembly and secretion by intestine
ApoB100LDL particle uptake by extrahepatic cells
ApoC-IILipoprotein lipase activation (defect -> Familial Hyperchylonmicronemia Type I)
ApoE-3 and 4VLDL and chylomicron remnant uptake by liver cells (defect -> Familial Dysbetalipoproteinemia Type III)
PKU is either from deficiency of PheHydroxylase ORTHB
B6 pathwaysTransamination, decarboxylation, heme and neurotransmitter synthesis
Neurotoxicity in MUD is fromLeucine accumulation
Maple syrup smell fromIsoleucine
CarnitineFatty Acid degradation, cytoplasm to mitochondria matrix.
Key enzymes in KetogenesisCAT II (Acyl Carnitine -> Acyl-CoA) and Aceyl-CoA Dehydrogenase.
Skeletal muscle carnitine deficiencyMyoglobinemia, weakness following exercise, elevted muscle triglycerides, hypoketonemia
Systemic primary carnitine deficiencyinherited defect in transport of LCFAs into the mitochondria; toxic accumulation. Causes weakness, hypotonia, and hypoketotic hypoglycemia.
MCAD/ Medium Chain Acyl-coA Dehydrogenase Deficiency presentationHypoglycemia and Hypoketonemia
Oxidation of FA leads to more or less energy per carbon atom vs carbMORE
HbC mutationLysine instead of Glutamic Acid
HbS, anoxic conditions leads toAggregation of Hb molecules/ polymerization -> meshwork of fibrous polymers.
What promotes sicklingLow oxygen, Increased Acidity and Low Blood Volume
HbS will allowHydrophobic interaction among Hb molecules. Globin chains normally are compactly folded due to nonpolar hydrophobic residues in interior and charged polar residues on surface.
G6PD CausesFava Beans, Specific Meds (Primaquine, Sulfa) and Infections
HMP Shunt/ Pentose Phosphate Pathway occurs inLactating mammary glands, liver, adrenal cortex, RBCs
Ketogenesis will deactivateAcetyl-coA carboxylase, which makes Malonyl CoA and then FA.
NADPH is energy butIt cannot be used to convert ADP to ATP
NADPH is active in liver, adrenals because it is needed forFA, Cholesterol and Steroid synthesis
Leading strand is which direction of replicaton forkTOWARDS
DNA polymerase IOnly bacterial DNA polymerase with 5’ to 3’ exonuclease activity. Excision repair enzyme and removes RNA primers.
Alpha-amanitin in death cap mushroomsInhibits RNAP2 (which makes mRNA, largest RNA). Causes severe hepatotoxicity.
Rifampin inhibitsRNAP in prok (recall, Prok only have one RNA poly to make all 3 kinds of RNA).
Hemoglobin S results from what mutationValine, nonpolar AA, replaces Glutamate, negatively charged. Affects speed across electrophoresis.
Hemoglobin C results from what mutationLysine, positively charged AA, replaces Glutamate, negatively charged. Affects speed across gel electrophoresis. Slowest.
Propionyl-coA (-> methylmalonyl-CoA) can be made from what amino acidsValine, Isoleucine via oxidative decarboxylation via branched chain alpha ketoacid dehydrogenase. Threonine and Methionine too.
Arginine to Ornithine via Arginase is what type of reactionHydrolysis.
Methylmalonyl coA to Succinyl coA is what type of reactionIsomerization. Also requires B12 for Methylmalonyl coA Mutase.
Hydroxylation thinkProline and Lysnine residues of collagen hydroxylated post translationally by prolyl and lysyl residues.
Transamination requiresB6.