Make Biochem MY BITCH Flashcards
What are the classical and vascular types of Ehlers Danlos syndrome
Classical is joint hypermobility adn seen with mutaiton in type V collagen
Vascular is vascular and organ rupture and see deficient Type III collagen
What is going in on uniparental disomy?
Whats dif between Heterodisomy and Isodisomy
offspring gets 2 copies of chrom from 1 parent,none from other:
Herodisomy = meiosis I error
Isodisomy = meisosis II error
What do we treat a pt with HGPRT deficiency with?
allopurinol (or febuxostat would be second line)
Explain structure of cilia and the disease caused by Dyenin arm defect
9+2 arrangement of microtubles; axonemal Dynein-ATpase likns peripheral 9 doublets–> see bending of cilium by sliding
Kartageners: immotile cilia d/t dyenin arm defect: intertility (dsfnx sperm and dsfnx fallopian tube), bronchiectasis, recurrent sinusitus, situs inversus
RLS in Urea cycle
Carbomyl Phostphate Synthetaes I
+ N-acetylglutamate
What are the 3 steps for Elongation in protein synthesis
- Aminoacyl tRNA binds to Asite (excpet for initator methionine)
- rRNA catalyxes peptide bond formation, transfers growing polypeptide to AA in the A site
- Ribosome advances 3 NTs toward the 3’ end of mRNA, moves the tRNA to the p site
RLS in Glycogenesis
Glycogen Synthase
+ Glucose-6-P, +insulin, +cortisol
-glucagon, -Epi
Key steps in Protein synthesis during Initiation
Initiated by GTP hydrolysis and initiation factors put together the 40S ribosomal unit with the initiator tRNA–> then released when mRNA and ribosomal 60S assemble with them
= 80S
RLS in Cholesterol Synthesis
HMG-CoA reductase
+insulin, +thyroxine
-Glucagon -Cholesterol
Enz Deficiency responsible for SCID causing excess ATP and dATP imbalance in the nucleotide pool
Adenosine Deaminase: causes feedback inhibition on ribonucleotide reductase thus decrease DNA synthesis
RLS in ketogenesis
HMG-CoA synthase
Stain for the following
CT
Muscle
Epithelial cells
NeuroGlia
Neurons
Vimetin = CT
DesMin = Muscle
Cytokeratin= epithelial cell
GFAP = Neuroglia
Neurfilaments = Neurons
What happens when we increase ethanol metabolism in regards to NADH/NAD+
Will increase NADH/NAD+ ratio in liver; leads to
Pyruvate –> malate (lactic acidosis)
OXA–> malate (prevents gluconeogenesis = fasting hypoglycemia)
Glyaldehyde-3-P –> Glylcerol-3-P (causes hepatosteatosis)
Site of synthesis of secreatory proteins and N-linked oligosacharides addition to proteins
vs
unattached and synthesis of cytosolic and organellar proteins
vs
synthesize and secreate peptide NTs for secreation
Rough Endoplasmic reticulum
Free ribosomes
Nissl bodies
Amino Acids necessary for PURINE synthesis
Purines make me GAG: glysine, Aspartate, Glutamine
RLS in FA synthesis
Acetyl-CoA Carboxylase (ACC)
+insulin, +citrate
-Glucagon -Palmitoyl CoA
EnZ takes Ethanol–> Acetaldehyde
EnZ takes Acetaldehyde–> Acetate
What drugs inhibit these enZ
Ethanol –> Acetaldehyde via Alcohol Dehydrogenase and inhibited by Fomepizole
Acetaldehyde–> Acetate via Acetaldehyde Dehydrogenase and inhibited by Disulfiram
EnZ deficiency responsible for SCID
Adenosine Deaminase deficiency
What makes rRNA, mRNA and tRNA and what does alpha-amanitin do?
RNA pol I = rRNA
RNA pol II = mRNA (inhibited by alpha amanitin from mushrooms=hepatotoxic)
RNA pol III= tRNA
*prokaryones only have 1 RNA polymerase that makes all these
Prokaryotic only, degrades RNA primers and replaces them with DNA; can excise in 5’–3’ direction
DNA polymerase I
Differences in following mutations;
Silent
Missense
Nonsense
Frameshift
silent: NT substitute for codes for same AA; often in 3rd position (tRNA wobble)
MIssense: NT substitution in changed AA (like in SS disease)
Nonsense: NT substitution that codes for early stop (UAG, UGA, UAA)
Frameshift: Deletion or insertion resulting in misreading of downstream NTs; get truncated shitty protein
normally inhibit G1 to S progression, mutation here results in unrestrained cell division
p53 and Rb
What is the start codon and what does it code for?
What are the stop codons?
Start = AUG; codes for methionine
Stops: UAA, UGA, UAG
RSL in De novo pyrimidine synthesis
Carbamoyl Phosphate Synthetase II
Difference between Indirect and Direct ELISA
Indirect: uses test antigen to see if a specific antibody is present in the pts blood; a secondar antiB coupled to color generating enZ is added to detect first antibody
Direct: uses a test antibody to see if specific antiG present in pts blood; secondary antoB coupled to color generating enZ to detect it
RLS in Glycogenolysis
Glycogen Phosphorylase
+Epi, +Glucagon +AMP
-G-6-P, - insulin, -ATP
3 yo child comes in that shows signs of MR. Parents note that he has violent behaviors and often slaps his face. His labs show Hyperuricemia.
Dx?
Cause?
Tx?
Lesch-Nyan syndrome
deficiency in purine salvage from absent HGPRT
also (hyperuricemia, Gout, Pissed off, Retardation and dysTonia)
tx: Allopurinol or Febuxostat
Golgi is key distribution for proteins and lipids from ER–> vesicles and plasma membrane
Modifies ____to serine and threonine and _____ to aspergine
Most importantly puts this on proteins that are destined for the lysosome
O-oligos to serine and threonine
N-oligoon aspartine
***Mannose-6-Phosphate for lysosomal trafficking
Where RNA polymerase and other TFs bind to DNA upstream from gene locus; AT RICH sequence with TATA box and CAAT boxes
mutation here results in decreased level in gene transcription
Promoter region
Congentital microdeletion of short arum of Chrom 5 (46XX or XY) what is this and what do we see associated
Cri-du-chat
microcephaly, ID, high pitched mewing (cat like) cry, epicanthal folds and VSD
Mother comes in with her 3 yo daughter. She is worried she is falling behind her developmental milestones, both physically and mentally. The daughter has hypotonia and brittle, kinky hair. Dx and cause
Dx is Menkes diesase: CT disorder d/t impaired Cu absorption and transport: see decreased activity of lysyl oxidase (Cu is a cofactor) = brittle hair, MR, hypotonia
Membrane enclosed organelle key in catbolism of VLCFA, branched chain FA and AA, has oxidase + catalse to metabolize alcohol to make plasmogen
and
Barrel shapped protein that degrades damaged or ubiquitin tagged proteins and depends on Ca++
Peroxisome
Proteosome
Difference btwn these single strand DNA repair mech:
Nucelotide Excision repair
Base excision repair
Mismatch repair
Nucleotide excision repair: Endonucleases release oligoNT with the damaged base; DNA polymerase fills gap then ligase fills and reseals
Base excision repair: Base-specific glycolysase sees altered base and creates AP site; then one or more NT removed by AP-endonuclease that cleave the 5’ end, lyase cleaves the 3’ end and DNA pol fills the gap
Mismatch repair: newly made strand is recongnized as mismatched then get remoeved and gap is filled
What are the key nuclear localizing signals necessary to get in and out of nucleus?
Proline, Arginine, Lysine; need to be PALs to get in the nucleus club! and it requires ENERGY to get in
What are p-bodies (this is for you Megan!)
mRNA quality control occurs at cytoplasmic p-bodies that hve exonucleases, decapping enZ and microRNAs: mRNAS that can be sotred here for future translation
What metabolism takes place in the Cytoplasm
Glycolysis, FA synthesis, HMP shunt, Protein synthesis (RER), steroid synth (SER) and cholesterol synthesis
What are the key steps in collagen synthesis and where do they occur?
- Synthesis in RER; make collagen alpha chains = precollagen (Gly-X-Y)
- Hydroxylation (RER) of specific proline and lysine residues (need vit C)
- Glycosylation (RER) of pro-alpha-chains residues and mae procollagen by H+ and S-S bonds–> triple helix of 3 alpha chains (CC = Osteogensis Imperfecta)
- Exocytosis of procollagen to ECM
- Proteolytic processing OUTside fibroblast :Clevage of S-S bonds to get insoluble tropocollagen
- Cross-linking (outside fibroblast) make Covalent Lysine-Hydroxylysine links to reinforce collagen fibrils
What metabolism occurs in the Mitochondria
Fatty acid oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation
Rare disorders, often prsent with myopathy, lactic acidosis and CNS disease. Muscle biopsy shows ragged red fibers
Mitochondrial myopathies; has transmission only through the mother
RSL in
Normal fnx of Na/K pump?
What effect does Oubain have on the Na/K pump?
What about Glycosides?
Pump 3 Na out, bring 2 K+ in–> the loss of Na+ creates a drive for the Na/Ca+ exchange (bring Na+ in and Ca++ out) to maintain low intracellular Ca++ in the heart for less cnx
Oubain inhibits via binding to K+ site
Glycosides (digoxin) will block Na/K pump thus get increase in intracellular Ca++ and increase force of cnx
Difference btwn Southern, Northern, Western, S.Western blot
Southern: electrophoresis of DNA which is then visualized
Northern: RNA sample is electrophoresed; reflects level of gene expression
Western: protein is electrophoresed (confirmatory after HIV+ELISA)
S.Western: DNA-binding proteins are labeled
What are the Irreversible steps in Glycolysis?
glucose–> G-6-P by Hexokinase or Glucokinase
Fructose-6-P–> Fructose 1,6 Bis PHosphate by Phosphofrucktokinase-1 (RLS)
PEP–> Pyruvate via Pyruvate kinase
What steps in glycolysis requre ATP?
What steps Generate ATP?
Need ATP: Glucose–> G-6-P by hexo or glucokinase and
Fructose-6-P –> Fructose 1,6 Bisphosphate
Generate: 1,3 BPG–> 3-PG and
PEP–> pyruvate
Regulation by F2,6 BP
What 2 enZ are same bifuncitonal enZ and how are they regulated?
FBPase-2 (fructose bisphosphatase-2) and PFK-2 (phosphofructokinase-2) are the same bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A.
Explain the regulation of PFK-2 and FBPase-2 in the fed and fasting state
Fasting state: HIGH glucagon–> Increased cAMP–> Increased protein kinase A–> Increased FBPase-2, and DecreasedPFK-2: less glycolysis, more gluconeogenesis.
Fed state: HIGH insulin–> Decreased cAMP–> Decreased protein kinase A–> Decreased FBPase-2, Increased PFK-2, more glycolysis, less gluconeogenesis.
What Products do we get from the TCA cycle?
Where does the TCA cycle occur?
What is the RLS in this processes?
The TCA cycle produces: 3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl-CoA = 10 ATP/ acetyl-CoA (2× everything per glucose).
occur in the mitochondria.
RLS: Isocitrate Dehydrogenase
What is the location and purpose of the Electron transport chain
What role does NADH and FADH2 play?
NADH electrons from glycolysis enter mitochondria via the malate-aspartate or glycerol-3- phosphate shuttle. FADH2 (=1.5ATP) electrons are transferred to complex II (at a lower energy level than NADH = 2.5 ATP).
The passage of electrons results in the formation of a proton gradient that, coupled to oxidative phosphorylation, drives the production of ATP.
What is the Respiratory Burst?
What role does it have in disease pathology?
Activation of phagocyte NADPH oxidase complex (in neutrophils and monocytes) to use O2 as a substrate. Key in immune response–> get rapid release of ROS
NADPH key for generation and neutralization of ROS
Myeloperoxoidase is blue-green heme containig pigment that gives sputum its color
CC: Chronic granulomatous disease: high risk for inection by catalase + species (S.aureus, Aspergillus) that acan neutralize their own H2O2 and leave phagocytes without ROS to fight infections
Glucose 6 Phosphate DH defiency has implications in several disease pathologies.
What is it’s role in anemias and infections?
NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides.
LOW NADPH in RBCs leads to hemolytic anemia due to _poor RBC defense a_gainst oxidizing agents (e.g., fava beans, sulfonamides, primaquine, antituberculosis drugs).
Infection can also _precipitate hemolysis (_free radicals generated via inflammatory response can diffuse into RBCs and cause oxidative damage).
You are doing rotations in the heme clinic and your attending has you looking at blood smears. He tells you one of them has a pt with G6PDH deficiency. What will you see on the slide? What is the inheritance?
Heinz bodies—denatured Hemoglobin precipitates within RBCs due to oxidative stress.
Bite cells—result from the phagocytic removal of Heinz bodies by splenic macrophages. Think, “Bite into some Heinz ketchup.”
X-linked recessive disorder; most common human enzyme deficiency; more prevalent among blacks.malarial resistance.
What enZ takes Glucose–> Sorbital to trap it in the cell (will create osmotic gradient)?
What can sorbital be further converted into to avoid this osmotic gradient?
What cells lack the above enZ thus are at risk for osmotic damage?
Glucose–> Sorbital via aldose reductase.
sorbitol –> Rructose using sorbitol dehydrogenase;
tissues with an insufficient amount of this enzyme are at risk for intracellular sorbitol accumulation, causing osmotic damage (e.g., cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in diabetes).
*Schwann cells, retina, and kidneys have only aldose reductase. Lens has primarily aldose reductase.
What is the purpose of the Urea cycle?
Amino acid catabolism results in the f_ormation of common metabolites_ (e.g., pyruvate, acetyl- CoA), which serve as metabolic fuels. Excess nitrogen (NH3) generated by this process is converted to urea and excreted by the kidneys.
Newborn baby is showing signs of Hyperammonium
You draw labs and it shows the following:
High Orotic acid in blood and urine
LOW BUN
DX?
Ornithine tranxcarbamulase deficiency
Most common urea cycle disorder_. X-linked recessive_
Interferes with the body’s ability to eliminate ammonia. Often evident in the first few days of life, but may present later. Excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway).
Findings: HIGH orotic acid in blood and urine, LOW BUN, symptoms of hyperammonemia. No megaloblastic anemia (vs. orotic aciduria).
Major AA responsible for transfering Nitrogen to the liver for disposal
During catabolism fo proteins, AA groups are transferred to Alhpa-ketoglutarate to form glutamate; which is then processed in liver to make urea and is primary disposal form of nitrogen in humans.
Alanine
