MCM Review Flashcards
What is the only source of pluripotent stem cells?
Cells of the inner cell mass
What is the problem in methemoglobin?
Iron is in its ferric state (Fe3+) and will not bind oxygen
Differentiate direct vs indirect methemoglobin
Direct –> genetically linked
Indirect –> oxidation by other compounds
What kind of shift does methemoglobin cause?
Left shift of oxygen curve
What kind of shift does anemia induce?
Anemia causes a right shift of the oxygen curve (decreased affinity
A patient has a blood oxygen content of 17.25 mL/dL and a hemoglobin concentration of 15.1 g/dL. The patient’s oxygen saturation is best described as which of the following?
A. Normal oxygen saturation (97-99%)
B. Decreased oxygen saturation (<97%)
C. Maximum oxygen saturation (100%)
B Decreased oxygen saturation (<97%)
1.34 mLO2/1gHb x 15.1g/dL
How many mL of oxygen are there per gram of hemoglobin?
1.34 mL O2/1 gHb
What clinical situations could indicate a left shift of oxygen to blood?
Polycythemia
Methemoglobemnia
What is primary polycythemia (Vera)
⬇️ EPO
Extra RBCs
⬆️ blood volume x2
⬆️ viscosity
normal CO
Why are silent mutations not harmful?
First two letters of codon often the same, but the third is able to be 3 separate codons so the same amino acid product is still possible
What mutations of DNA can be significantly detrimental?
Nonsense and frameshift mutations
What causes Sickle cell anemia?
Single base substitution of Glu for a Val (hydrophobic, neutral)
What common energy expenditure is constant for all three steps of mRNA translation?
All three steps utilize GTP
What are the prokaryotic elongation inhibitors?
Tetracycline –> binds 30S, blocks tRNA entry
Chloramphenicol –> inhibits peptidyl transferase
Clindamycin/erythromycin –> binds 50s, blocks ribosomal translocation
What are the eukaryotic elongation inhibitors?
Cycloheximide –> inhibits peptidyl transferase
Diptheria Toxin –> inactivates GTP-eEF2
Shiga Toxin/Ricin –> binds 60s, blocks tRNA entry
What is the role of puromycin?
A eukaryotic elongation inhibitor that shares a similar structure to tyrosyl-tRNA
Enters A site and causes premature stop
What do initiation factors attached to small ribosomal subunit do?
What do initiation factors attached to met-tRNA do?
Small ribosomal subunit –> promotes binding of codon and anticodon of tRNA
IF attached to met-tRNA –> hydrolyzes GTP to provide energy for formation of initiation complex
Where are proteins destined that are made in the cytoplasmic pathway?
Cytoplasm
Mitochondria
Nucleus
What is the nuclear translocation signal?
KKKRK (tryptophan rich signal)
What is the mitochondrial translocation signal
An N-terminal hydrophobic α- helix peptide
What residues does O-glycosylation target?
Ser and Threonine
What does N-guyscosylation target?
Asn and Gln
What residues does phosphorylation target?
Ser, Tyr, Asp, Thr, His
Hydroxyls (OH)
What residue does disulfide bonding target?
Cystine residues
What may happen if a diabetic has an over-abundance of glycosylation?
Cataract formation in the eye
What happens in Alzheimer’s Disease?
A mutated gene that produces amyloid precursor protein (APP) formation of neurotic plaques
Supplementation with lys may
What happens in Mad Cow disease?
Introduction of prions (misfolded proteins) that induce the same formation in their counterparts
What happens in Huntington’s Disease?
Protein aggregations in the brain CAG repeats = polyglutamine (polyQ) tract
The abnormal Huntington protein (mHTT) forms intramolecular hydrogen bonds and aggregates
What happens in Parkinson’s disease?
Mutated α-synuclein results in aggregates that form Lewy bodies
Function form is an α-helix while the febrile form is β-sheet
Results in neuronal death of the midbrain and a lack of available dopamine
Describe endocrine signaling?
Long distance Signaling - hormone
Describe paracrine signaling?
Signal diffused to neighboring cell - NMJ
Describe autocrine signaling?
Signaling cell is the targeting cell
Where do hydrophobic signal target?
The nucleus
Where do small polar hydrophilic signals target?
An EC receptor that utilizes secondary messengers
What are some sensory input for GPCRs?
Photons, ions, amino acids
An active GPCR switches out ________ for ______ via ________
GDP, GTP, GEF
What is the role of Gαs?
Stimulates production of cAMP via adenylate cyclase ultimately activating PkA
What is the role of Gαi
Inactivates adenylate cyclase = no PKA
What is the role of Gαq
Activates PLC (phospholipase C) causing the cleavage of PIP2 –> IP3 & DAG (ca2+ also)
What is the role of G protein receptor kinases? What is the end goal?
End goal - to desensitize the G protein
GRK phosphorylates GPCRs to which Arrestin can bind (3rd IC loop) and inhibit
What’s happening in cholera?
Gαs is constantly active. The resulting cAMP keeps Cl- channels constantly open
What’s happening in Pertussis?
Gαi is inhibited, excessive cAMP produced via adenylate cyclase
Dried out airways
What pathways are activated by RTK signaling?
Ras - dependent
Ras - independent
What blotting technique allows for visualizing of protein?
Western blot
What blotting technique visualizes DNA?
Southern blotting
What blotting technique visualizes RNA?
Northern blot
What is the problem with the heat-stable DNA polymerase used in PCR?
It has no proofreading capability an is described as a “dirty” method
What is RFLP used for?
Forensics
What is VNTR (variable number of tandem repeats)
Diagnostics of disease (Huntington’s)
What is one use of recombinant gene technology?
Insulin production (better than wild type)
What is the use of ELISA?
Practical use –> HIV ag
What’s the difference between indirect and sandwich ELISA?
Indirect –> Target is Ag
Sandwich –> target is Ab
What is the only version of totipotency?
Zygote
What are the examples of pluripotency?
- ) ICM of a blastocyst
2. ) iPS
What can be associated with embryonic stem cells?
Teratomas, cancer, unrestricted growth
What growth factors produce an adipocyte?
Retinoic acid + insulin + thyroid hormone
What growth factors produce a neuron?
Retinoic acid
What potency is cord blood?
Multipotent
What potency are fetal stem cells?
Multipotent
What potency are hematopoietic stems cells?
Multipotent
What change in potency does iPS induce?
Taking a somatic multipotent cell and changing into a pluripotent cell
What are 5 important growth factors needed to induce iPS?
Oct 3/4, Sox-2, Myc (n-Myc and c-Myc), Nanog, FoxD3
Does urobilinogen have color?
No, it’s translucent
Discern PKU from Cystic Fibrosis
Multiple genotype, one phenotype - Cystic Fibrosis
One genotype, multiple phenotypes - PKU
What does chemotaxis use to change
Monomeric G protein –> pip3 –> Ras –> ARP –> Rho
What is the consequence of an intra-hepatic jaundice
Build-up in the blood of conjugated and unconjugated billirubin
Increase in ALT and AST
What’s the consequence of post-hepatic jaundice
Elevated blood levels of conjugated billirubin
Break down of heme, what is the first enzyme to act on heme? (Rate-limiting step before the liver)
Heme oxygenase
What type of signaling is Talin and FAK?
Talin (in –> out)
FAK (out –> in)
What is a good thing to know about FAK?
It’s a drug target
What happens in secondary polycythemia?
Abnormal CO
⬆️ EPO
⬆️ RBCS
What changes in Physiologic polycythemia?
Normal CO
⬆️ RBCs
⬆️ EPO
What does activation of the RAS-dependent pathway lead to?
Gene transcription (increased glucokinase transcription)
What does the activation of the RAS-independent pathway lead to?
Alteration of protein and enzyme activity - GLUT 4 sequestering activation of glycogen synthase
What are important growth factors found in pluripotent cells?
Cripto and GDF-3
What two diseases are related to intra-hepatic jaundice?
Criggler-Najjar syndrome
Gilbert syndrome
What are all the cyclin-Cdks and what phases do they operate in?
Cyclin - D | D | E | A | A | B
Cdks - 6 | 4 | 4 | 2 | 2 | 1
Phase -G1|G1| S | S |G2|G2
Discern Prader Willi Syndrome from Angelman Syndrome
Prader Willi - paternal chromosome deletion (maternal silenced)
Angelman Syndrome - maternal chromosome deletion (paternal silenced)