Biochemistry - UWorld Flashcards
Proteins transcribed by the lac operon
Lac Z = beta-galactosidase, hydrolyzes lactose to glucose and galactose
Lac Y = permease, allows lactose to enter the bacteria
Lac p = binding site of RNA polymerase
Lac I = constitutively produces Lac repressor protein, lactose binds this and prevents the repressor from binding to the operator site
Glucose’s effects on the lac operon
Glucose increases intracellular ATP levels, which deactivates adenylate cyclase, reduces cAMP levels and reduces CAP binding to the promotor region.
Consequence of the deltaF508 mutation that causes cystic fibrosis
This results in improper posttranslational folding and shunting of the improperly folded protein to the proteosomes instead of the epithelial membrane
Protein mutation in the Ras-MAP kinase pathway that commonly predisposes to cancer.
Mutation in Ras that makes it resistant to GTP hydrolysis or mutation in GAP that cannot hydrolyze GTP results in constitutive activation of Ras leading to overactivation of genes and cancer
Examples of molecules that use the PLC signalling pathway
alpha1, M1, M3, V1, H1, oxytocin, AT II, TRH, GnRH
How is NO synthesized?
Arginine + O2 is converted to NO by NO synthase
Proteins that can be labeled by a DNA probe
Proteins that can actually bind DNA: transcription factors (n-myc), steroids, thyroid proteins, vitamin D receptors, retinoic acid receptors, DNA replication and transcription proteins.
Clinical signs of OTC deficiency
Elevated carbamoyl phosphate, orotic aciduria (due to shunting of carbamoyl phosphate to thymine synthesis), neurological disorders and elevated serum NH3.
Components of telomerase
Reverse transcriptase component: TERT
RNA template: TERC
TERT repeatedly reads TERC TTAGGG to add telomeres to the end of DNA and does not need a template.
Why are cancer cells immortal?
They have high telomerase activity and do not undergo cell death initiated by shortening of their telomeres.
Consequence of vitamin A toxicity
Acute: nausea, vomiting, vertigo, blurred vision
Chronic: alopecia, dry skin, HLD, hepatoxicity, HSM and vision complaints
Teratogenic: microcephaly, cardiac abnormalities and 1st trimester fetal death
Riboflavin deficiency
Cheilosis, corneal vascularization
Vitamin C overdose
False negative stool guiac, bloating
Vitamin E overdose
Hemorrhagic stroke and infant NEC
Embryonic hemoglobin in the yolk sac
Two zeta and two epsilon chains (Hgb Gower)
Two alpha and two epsilon chains (Gower 2)
Two zeta and two gamma chains (Hgb Portland)
Fetal hemoglobin
Two alpha and two gamma chains. Replaces all embryonic Hgb by 14 weeks.
Hemoglobin A2
Two alpha and two delta chains
Factors that promote RBC sickling
Anoxia, acidity, 2,3-BPG binding and hypovolemia
What form of Hbg is stabilized by 2,3-BPG
Taut, this results in decreased Hgb affinity for O2 and increased peripheral O2 unloading
5 factors required by branched chain alpha-ketoacid dehydrogenase, pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase
"Tender Loving Care For Nancy" Thiamine Lipoate CoA FAD NAD
2-5 month old infant with irritability, developmental delay, poor muscle tone and liposomal galactocerebroside accumulation.
Krabbe disease due to autosomal recessive deficiency in galactocerebrosidase.
Homeobox genes code for…
DNA transcription factors that govern the proper placement of appendages
Adult with arthritis and blue-black deposits in the cornea and aricular cartilage. His urine sample turns black when exposed to air.
Alkoptonuria due to deficiency in the enzyme homogentistic acid dioxygenase. Accumulation of homogentistic acid results in these black-blue deposits.
18 month old who developed normally, but suddenly lost motor and language skills and constantly wrings her hands. Physical exam reveals decreased head size.
X-linked MECP2 mutation causing Rett syndrome.
Enzyme that increases use of PRPP in patients with Lesch-Nyhan syndrome
PRPP amidotransferase, this is because deficient HGPRT results in increased requirement for de novo purine synthesis, which goes through this enzyme.
A patient has acroparesthesia, acrokeratomas (dark red, non-blanching macules/papules between umbilicus and knees) and culture demonstrates failure to metabolize ceramide trihexose. What will likely result in this patient’s death?
Fabry disease due to inherited deficiency in alpha-galactosidase A. This results in accumulation of the globoside ceramide trihexose in tissue and patients die from renal failure if this enzyme is not supplemented.
How to tell failure of meiosis I vs. meiosis II on RFLP analysis for trisomy 21
Since you would inherit both sister chromatids in failure of meiosis II, there would be two bands with one band being thicker in the child. In failure of meiosis I, the child would have 3 different chromosomes.
Principle forces stabilizing secondary protein structure
Hydrogen bonds
Enzyme defect in a patient with early onset acute coronary syndrome, ocular lens displacement and intellectual disability with elevated methionine levels. Treatment?
Cystathione beta synthase. Patients cannot form cysteine from homocysteine, making cysteine an essential amino acid in their diet and homocysteine levels rise leading to hypercoaguability. Also, homocysteine buildup can result in hypermethioninemia. Treat with methionine restriction and pyridoxine (vitamin B6) supplementation to augment cystathione synthase’s activity.
Type II glycogen storage disease
Pompe disease:
Why do methylmalonyl CoA and methionine build up in patients with B12 deficiency
B12 is necessary for the enzymes methionine synthase and methylmalonyl-CoA mutase to synthesize methionine and succinyl-CoA, respectively. When these are absent, homocysteine builds up with reduced methionine synthase activity and methylmalonic acid builds up due to reduced methylmalonyl CoA mutase activity.
***Note that methylmalonic acid is disrupts myelin synthesis and results in subacute degeneration of the posterior column and lateral corticospinal tracts.
Why does B2 deficiency result in normocytic anemia?
It is needed for RBC glutathione reductase. Deficiency can result in hemolysis secondary to increased RBC stress.
Which monosaccharide is metabolized fastest through glycolysis
Fru-1P. This is because it reacts with aldolase B and splits to DHAP and glyceraldehyde. The glyceraldehyde can then enter glycolysis by conversion to glycerol-3P by triokinase. This allows it to bypass the rate limiting step of glycolysis, PFK-1.
Metabolic intermediate that is deficient in the brain of a patient with hepatic encephalopathy
NH4+ causes increased conversion of Glu to Gln in the brain, depleting neurotransmitter stores. Increased Gln in the astrocytes increases cellular osmolarity and causes cellular swelling. Also, glutamate depletion results in shunting of alpha-ketoglutarate to glutamate by glutamate dehydrogenase, depleting the neurons of alpha-ketoglutarate for the TCA cycle.
Site of oxidation of VL chain FAs and alpha oxidation
Peroxisomes
How do you get niacin, serotonin and melanin if you never eat it?
Endogenous synthesis from tryptophan.
Pyrimidine precursor molecule
Orotic acid
How do RBCs sacrifice ATP in times of hypoxemia
RBCs need to produce 2,3-BPG from glycolysis and bypass the ATP generated from converting 1,3-BPG to 3-PG. They instead convert 1,3-BPG to 2,3-BPG, which decreases Hgb’s affinity for O2 and increases unloading.
Cause of familial erythrocytosis
A beta-globin gene mutation results in decreased binding of 2,3-BPG. Normal Hgb has His and Lys residues that are positively charged and create a binding pocket for the negatively charged 2,3-BPG. Mutations in this binding site decrease affinity for 2,3-BPG, increase affinity for O2 and make the Hgb similar to HbF.
HbC
Glu -> Lys mutation causing Hgb to form hexagonal crystals and mild chronic hemolytic anemia.
Why is alpha-thalassemia so fatal?
Deficient alpha chain results in Hb Barts (4 gamma chains) and Hb H (4 beta chains), both which have very high affinities for O2 and do not deliver it to peripheral tissues.
A child presents with photosensitivity and pellagra-like skin rash. She also has waxing and waning ataxia. Labs show amino aciduria restricted to neutral amino acids. Her symptoms improve significantly with niacin supplementation and a high protein diet. What is causing her symptoms?
Hartnup disease is due to defect apical enterocyte and renal transport of tryptophan, resulting in niacin deficiency because niacin is synthesized from tryptophan.
HMP shunt rate limiting enzyme
Glc-6P DH. This converts Glc-6P to 6-phosphogluconolactone and one molecule of NADPH that can be used to reduce glutathione in RBCs. Remember, the next step is the conversion of 6-phosphogluconolactone to ribulose-5P + the second NADPH by 6-phosphogluconolactone dehydrogenase.
t(15;17)
M3 AML due to fusion of the AML gene with the retinoic acid receptor that prevents myeloblasts from differentiating.
Mutated cancer genes that result in EGF activation
ErbB1 small cell lung cancer and Her2/neu (erbB2)
Friedrich’s ataxia pathophysiology
GAA repeats causes frataxin gene mutation, which codes for a mitochondrial protein imporatnt for respiration and iron hemostasis.
t(9;22)
Philadelphia chromosome results in BCR-ABL fusion and CML.
Mutation involved in classic galactosemia
AR mutation in galactose-1P uridyltransferase.
Nucleus that holds the cell bodies of cholinergic neurons
Nucleus basalis of Meynert
Xeroderma pigmentosa mutation
AR mutation in DNA excision repair.
HNPCC mutation
Mutation in DNA mismatch repair enzymes
Pyruvate carboxylase
Catalyzes the initial step of gluconeogenesis
Location of pentose-phosphate pathway
Cytosol only
Prokaryote vs. eukaryote DNA polymerase
Prokaryote: DNA polymerases I, II, and III
Eukaryote: DNA polymerase III does most of the work
Mutations associated with early onset Parkinson’s disease
Parkin, PINK-1 and DJ-1 gene mutations result in malfunction of a protein that normally tags protein aggregates for degradation via the ubiquitin-proteosome pathway. This results in aggregation and formation of Lewy bodies seen in Parkinson patients.
What causes skeletal muscle to increase glycogenolysis immediately upon contraction?
Muscle contraction releases Ca2+ which causes synchronized glycogen breakdown in muscle. EPI and glucagon bind Gs in the liver and increase cAMP levels. The elevated cAMP levels activate PKA, which activates phosphorylase kinase, which in turn phosphorylates and activates glycogen phosphorylase. In addition to Ca and EPI, reduced ATP and increasing AMP levels further activate glycogen phosphorylase, resulting in increased glycogenolysis.
1 year old child of Ashkenazi Jewish descent has HSM, progressive hypotonia and mental retardation. Liver and spleen biopsy shows foamy histiocytes with accumulation of sphingomyelin. Physical exam reveals a cherry-red macula.
Niemann-Pick disease due to deficiency of sphingomyelinase.
Genes commonly mutation in Ehlers-Danlos
Lysyl hydroxylase (presents with decreased hydroxyproline) or procollagen peptidase (presents with disulfide rich procollagen globular domains)…enzymes involved in the cytoplasmic processing of collagen
What makes up neurofibrillary tangles?
Hyperphosphorylated tau proteins (microtubule component)
Buspirone mechanism of action
5-HT1 receptor partial agonist
Treatment of organophosphate poisoning
Organophosphate poisoning results in irreversible inhibition of AChE. Treat with muscarinic antagonist atropine or pralidoxime (decouples organophosphates from AChE).
Huntington disease pathophysiology
Huntingtin gene mutation -> CAG repeats -> gain of histone deacetylation function in huntingtin protein -> silencing of genes necessary for neuronal survival
Enzyme deficiency that can cause Ehlers-Danlos
Procollagen peptidase deficiency results in lack of cleavage of the N and C terminals of procollagen to make it less soluble tropocollagen.
Cal per gram of protein, carbohydrate, fat and alcohol?
Protein and carbohydrate = 4
Fat = 9
Alcohol = 7
Enzymes that correct thymidine dimerization
UV-specific endonuclease. This is the enzyme absent in xeroderma pigmentosum.
Enzyme that corrects DNA mismatch
3’ -> 5’ exonuclease. This is deficient in HNPCC
