Block 1 enzyme + pathways Flashcards
Limited proteolysis
Peptide hormones (insulin)
Clotting factors
Digestive enzymes (pepsinogen etc)
Ubiquitination
tags for proteasomal degredation
Acetylations/deacetylation
done to histones to regulate transcription
Phosphorylation vs. dephosphorylation
kinases & phosphatases
Glycosylation
Process to make glycoproteins and proteoglycans (i.e folding N-glycans in the ER’s lumen)
Hydroxylation
Process to make collagen and elastin
ADP-ribosylation (bacterial toxins)
Bacteria that cause overactive signaling pathways for themselves to use:
cholera (Gs) + pertussis (Gi)
Bacteria that inhibit signaling pathways:
Diptheria (Gs)
O-glycosylation (post-translational)
Glycosyltransferase glycosylated the OH-groups of proteins in the Golgi forming:
Protein-OH +UDP—> Protein-O-Sugar—> Mature-O-glycans—-> Targeting action sites for protein
Cytosolic Protein pathway (post-translational)
Proteins are made from Free Ribosomes —-> completed synthesis —-> gains signal sequence and is translocated to its site of action
Secretory Protein pathway
Free ribosomes make protein —> growing protein gains ER signal sequence —> Signal recognition particles see SSand stop synthesis —> protein is translocated into the ER —> transcolon opens and inserts the growing peptide into the ER’s lumen —> protein synthesis re-starts —-> protein is modified in the ER then packaged into vesicles
if the vessicle is coated in:
COP I it goes Golgi—-> ER (re-do)
COP II it goes ER—->Lumen
Clarthrin it goes trans golgi —> Lysosome (destroyed)
A protein’s activity is altered when a particular serine side chain is phosphorylated. Which of the following amino acid substitutions at this position could lead to a permanent alteration in normal enzyme activity?
Ser —-> Glu
A 39-year-old male truck driver presents with an overdose of methamphetamine (pKa = 10.0) consumed in an attempt to be alert at night for long drive. Which of the following statements regarding the treatment of methamphetamine overdose is most appropriate?
.
Ammonium chloride acidifies the urine, converting a larger fraction of methamphetamine to the unprotonated, uncharged form, which is poorly reabsorbed and thus more rapidly eliminated.
A patient with influenza has a fever of 101.8°F orally. The excess heat is dissipated throughout the body via a substance that can be best described by which one of the following?
dipolar molecule
Proteins, which are composed of amino acids, help transport lipids in the bloodstream. These proteins need to be able to cluster with other non-polar molecules and exclude water. Which of the following would best describe the side chains of these amino acids in the lipid transport proteins?
positive hydropathic index
Aspirin (pKa = 3.5) is largely protonated and uncharged in the stomach (pH 1.5). What percentage of the aspirin will be in this form at pH 1.5?
99%
Which peptide is less soluble in an aqueous environment, Ala-Gly-Asn-Ser-Tyr or Gly-Met-Phe-Leu-Ala?
Gly-Met-Phe-Leu-Ala
What will happen to the charge on His residues in a protein that moves from the cytoplasm to lysosome?
pronated
Is Val ionized when incorporated into a protein?
it’s not ionized
What effect will raising pH from an acidic value to the physiologic value of 7.4 have on neutral amino acid?
Deprotonation of the alpha-carboxyl group
A patient attempted suicide by ingesting 50 aspirin tablets. This led to a fairly severe metabolic acidosis. A decrease of blood pH from 7.5 to 6.5 would be accompanied by which one of the following changes in ion concentration?
A 10-fold increase in hydrogen ion concentration
The results from the blood amino acid screen show two elevated amino acids. A titration curve performed on one of the elevated species shows two ionizable groups with approximate pKs of 2.0 and 9.5. The most likely pair of elevated amino acids consists of
Leucine and isoleucine
Collagen synthesis pathway
Intracellular: RER makes 3 prepocollagen an they’re translated —-> It’s ER signal sequence is cleaved via protease into procollagen —-> In the ER’s lumen the procollagen is hydroxylated by vitamin “C” and then “O-glycosylation to form a triple helix + disulphide bonds —-> Procollagen leaves the cell and extended ends are cleaved into tropocollagen which is assembled into fibrils —> fibrils are cross-linked via lysyl oxidase and mature to collagen
Collagen 1,2,3,4
1= tough bone,
2= cartilage
3= skin (elhers danlos type 2)
4= basement membrane (elhers danlos type 1)
Protein kinases phosphorylate proteins only at certain hydroxyl groups on amino acid side chains. Which of the following amino acids contain side chain hydroxyl groups?
serine, threonine, and tyrosine
Endogenous DNA damage “ER Regulars Can Develop Fever + Shakes”
ExogenousDNA damage “ Exposure to UV Dims Skin & makes me BRAF! Drink, Break, & Fuel”
Repeating sequences = Replication errors (issue with DNA polymerase, can’t recognize preparing sequence)
Chemical= Depurination (cleaved N-glycosidic bonds between deoxyribose and purines, free radicals, & spontaneous deamination (mismatching)
UV radiation: Formed Dimers (bulk DNA and stop replication and BRAF mutation —-> melanoma
Ionization= Double stranded breaks + free radicals
Genetic replication
initiation “Oh Her Sweet Titty SLP!”
Elongation “Real People Prefer Pears 5–>3 long lagging days Past Lunch”
Termination
Prereplication complex searches and binds to ORI —> Helicase unzips DNA at replication fork —> Single stranded binding proteins keep single strands from reannealing —-> Topoisomerase (I Eukaryotes, 2/DNA gyrase loosens supercoils via : snapping strands, loosening the coils, and patching the strands
RNA primase makes RNA primers (10-12 sequences long)—> DNA polymerase binds and synthesizes DNA in 5-to-3 direction —-> leading is continuous (1 primer) and the lagging is discontinuous (many primers) —> DNA pol 1 can excise incorrect pairs in the 5-3 direction and replace it with dNTP’s and replace the primers—> Ligase will glue the ends of the Okazaki fragments together
DNA polymerase run into Telomerase (TTAGGG)
Xeroderma Pigmentosa “eXPerience & NERV DoMinate & Persevere”
Impaired Nucleotide excision repair causes build up of pyrimidine dimers due to UV damage; it causes dry skin, photosensitivity, and melanomas
TATA BOX
Eukaryotes “TEN” vs. Prokaryotes “PAT 35”
E= ~10Bps (prinbnow TATAAT) 5–> 3
P= ~35Bp (TTGACA)
RifamPINS
An antibiotic against RNA polymerase’s beta subunit to inhibit RNA synthesis
RNA Polymerases “1 RN”, “2 HaNds Can Tie Docks”, “3 SMall TRains, & 5 Safety Rails”
1= in nucleus it catalyzes rRNA synthesis
2= transcribes hnRNA & carboxyl-terminal domain regulates enzyme activity via phosphorylation
3= catalyses tRNA, 5sRNA, & smRNA synthesis
Transcription factors “Dumb BF Helps”
TFIID (binds TATA), TFIIB (binds RNA pol & TFIIF bound pol), TFIIE&H (bind to the rest to form the preinitiation complex)
Cappins “ CAPTain Prefers 5 Good, Trusty, People vs 7 Nasty Men”
RNA5’ Triphosphatase removes a phosphate —> Guanyltransferase hydrolyses GTP to GMP —> Methyltransferase adds a methyl to the nitrogen at the 7th position in the base guanine
DNA repair
Non-homologous repair “No HOMO Displays Boys”
Homologous repairs “ 2 HeaDs”
Nucleotide excision repair “ NERve”
Base excision repair “Gel PLease”
NHR= Double-stranded breaks
H= X2 DNA Duplexes no nucleotide loss
NER= Endonuclease removes damaged bases
BER= Glycosylate removes damages base and makes an AP site, AP-Endonuclease binds & cleaves 5’ + AP=Lyase binds & cleaves 3’, DNA polymerase replaces the bases and Ligase seals the ends of the strands
Cockayne syndrome “COCKs NEveR DuMP Full loads”
Mutated ERCC6(B)/8(A) causes improper NER (thymine-thymine dimers form during transcription and causes microencephaly, failure to thrive, developmental delay, & photosensitivity
inhibitors
Competitive “ CIty WiNe BAR MAKES FIne HeneSy”
Non Competitive “NIC LoVes All the RIBS & WiNe He Ate”
Irreversible “HAVe COAL LoVe”
COMP= Weak non-covalent bond to the active site (reversible), Fixed level of inhibitor allows increasing levels of the substrate to outcompete it, methotrexate, ace inhibitors, high Km, Ethanol, & Statins
NONCOMP= Low vmax, binds allosteric site, Reversible reaction, Inhibitor blocks Substrate, Weak non-covalent bond,. hyperbolic, Allopurinol
Irr= Binds active site of functional AA’S, hyperbolic, low vmax, cyanide, aspirin, organophosphates, lead
Allosteric enzymes “EAt CrACkerS PAL”
Enzyme modification
“TRANSFER PoKemon Ash”
“HYPER DOg”
Allosteric enzymes use allosteric effectors to bind to the allosteric site; this causes conformational changes in the active site to bind a specific substrate
Positive/active effector shifts the graph left (lower Km but higher affinity
Negative/Inhibitory effector shifts it right (higher Km but lower affinity
Transferases (protein kinase) phosphorylates functional AA side chains (via ATP as a PO4- donor) to turn the enzyme ON
Hydroxylases (Phosphatases) dephosphorylate the functional AA side chains to turn the enzyme OFF
Lygase/synthase “CAB”
Transferase “G-TRAAMP”
Hydrolase “PEG”
Oxidoreductase “OH DAM!”
Lyases/Synthetases “LAY tHe DEAD”
Lygase= Carboxylase (Biotin)
Transferase= Glycol-TR (UDP sugars), Acetyl-TR (Coenzyme A) Amino-TR (PLP, Vit B6, Pyroxidase), Methyl-TR (THF (folate) & SAM), Phospho-TR (ATP as PO4- donor)
Hydrolase= Peptidase (Protein), Esterase/lipase (fats), glucosidase/amilase (carbs)
Oxioreductase= Oxidase (heme), hydroxylase (NAD B3 Niacin, FAD B2 Riboflavin), Monooxygenase (Vit C. B3 Niacin)
Lyases= Hydroxylase/dehydroxylase, Deaminase, Decarboxylase (+PLP, Vit B6, pyridoxine)
Respiratory acidosis “CRAB BOB”
Respiratory alkalosis “PPPHHH”
Metabolic acidosis high ag (GOLDMARK) normal ag (HARDASS)
Metabolic Alkalosis “Basicity CaN’t Hurt GeLL HArdened Vaneers”
High AG “CATMUDPILES” Met acidosis
Causes of Lactic Acidosis “LAzy CROCS CHIll)
High AG + blurry vision “BAG VAM)
Methanol ingestion
Hydrophobic/NP “Good Ass Lures In Very Wet Money For Pimps”
Hydrophilic/Polar “ Too Sad Cops Question Your Name”
Acidic
Basic “Her Leggings Are Basic”
Neutral AA “ Sometimes Neutrality Causes Quagsire’s Yawns”
