bananas's version from 2015-06-03 18:42


Question Answer
Describe "beads on a string" = Chromatin structureDNA wraps around +charge histone octamer (lysine/arginine, made of 2 sets of H2A, H2B, H3, H4) to form nucleosome bead, H1 ties beads together (H1 is not in nucleosome core!)
Hetero vs euchromatinheterochromatin is condensed and not transciptionally inactive; Euchromatin is less condensed and transcriped
Which nucleotides are methylated and why?cytosine & adenine to allow mismatch repair enzymes to distinguish b/t old & new strands
Histone methylationinactivates transcription of DNA
Histone Acetylationrelaxes DNA coiling, allowing for transcription - adds (-) charge to (+) histones
Nucleotides and # of rings in structurepurines (A/G) have 2 rings, pyriamidines (C,T,U) have 1 ring
Deamination of cytosine?makes uracil
Which nucleotide-nucleotide bond is strongest?G-C has 3 H-bonds and is stronger than A-T (2 H bonds) - AT GC 2,3!!
higher G-C content indicates?higher melting temperature
AAs needed for purine synthesisglutamine, aspartate, glycine (GAG)
Nucleoside vs nucleotidebase+ribose (Side) vs base+ribose+phosphate (Tide) (linked by phosphodiester bond)
Uracil vs. thiamineuracil found in RNA and thymine in DNA

Pyrimidine & Purine Synthesis

Question Answer
purinesA, G (2 rings)
pyrimidinesC, T, U (one ring)
Purines made from what precursor?IMP
Purine synthesis pathwaystart with Ribose 5P-->PRPP--> --> --> --> IMP--> AMP or GMP
Purine synthesis requires what?glycine, aspartate, glutamine, C02 and THF
Pyrimidine synthesis pathwaystart with carbamoyl phosphate--> --> -->orotic acid + PRPP---> UMP-->UDP-->dUDP + CTP--->dUMP-->dTMP, requires aspartate, thymidylate synthase, dihydrofolate reductase, ribonucleotide reductase
Rate limiting enzyme of pyrimidine synthesiscarbamoyl phosphate synthetase II makes carbamoyl phosphate from glutamine and C02
Rate limiting enzyme of purine synthesisPRPP amidotransferase makes IMP from PRPP
Orotic acid + PRPP --> UMPUMP Synthase
UDP --> dUDP enzymeRibonucleotide reductase
dUMP --> dTMP enzymeThymidylate synthase
DHF --> THF enzymeDHF reductase
Hydroxyureainhibits ribonucleotide reductase (no UDP-->dUDP)
Used for: Melanoma, Sickle cell disease (increases HbF)
S.E.: Myelosuppression
6-mercaptopurine6MP blocks de novo purine synthesis aka the rate limiting enzyme PRPP amidotransferase
Used for: AML/ALL
S.E. increased toxicity w/ Allopurinol since 6-MP is metabolized by xanthine oxidase
6-thioguaninesame mechanism as 6MP - blocks de novo purine synthesis
Can be used w/ Allopurinol
5-fluorouracil5FU inhibits thymidylate synthesis (no dUMP--> dTMP
Used for: solid tumors (colon, breast, ovarian CA)
S.E.: irreversible myelosuppression --> give Thymidine; photosensitivity
Methotrexateinhibits dihydrofolate reductase so no dTMP
Used for: Liquid tumors (Leukemias); abortion, RA, psoriasis
S.E.: reversible myelosuppresion --> give Leucovorin (folinic acid); teratogenic
Trimethopriminhibits bacterial dihydrofolate reductase (less dTMP)
S.E.: Megaloblastic anemia, Leukopenia, Granulocytopenia (give Leucovorin)
Ornithine transcarbamoylase deficiency (OTC)involved in urea cycle = takes carbamoyl phosphate to citrulline so leads to an accumlation of carbamoyl phosphate, this is converted to orotic acid-->aciduria
Findings = increased orotic acid w/ hyperammonemia
Orotic aciduriano conversion of orotic acid--> UMP due to defect in orotic acid phosphoribosyltransferase or decarboxylase
autosomal recessive
Findings = orotic acid in urine, megaloblastic anemia (doesn't improve with B12 or Folate supplement), ...NO hyperammonemia
treat w/ oral uridine
HGPRTenzyme for transferring guanine or hyoxanthine on to phosphoribose to form purine nucleotides in purine salvage
Adenosine deaminase deficiencyexcess ATP/dATP imbalances nucleotide pool via feedback inhibition of ribonuc reductase-->prevents DNA synth-->decreased lympho count, **1 of major causes of SCID**
SCIDcan be caused by adenosine deaminase deficiency - adenosine builds up and is toxic to WBCs
treated by gene therapy
Lesch Nyhan syndromeXR deficiency of HGPRT which converts hypoxanthine-->IMP and guanine-->GMP, excess uric acid production--> HGPRT (Hyperuricemia, Gout, Pissed off, Retardation, DysTonia)

Genetic Codes and Mutations

Question Answer
Transition vs transversiontransItion (identical) is purine for purine substitution (or pyrimidine) whereas transVersion is conVersion between purine/pyrimidine
AUG codonstart- methionine in euks, f-MET in proks
Genetic code featuresunambiguous (1 codon=1 AA), degenerate/redundant (more than 1 codon may = same AA), non-overlapping (continous sequence of bases), universal (exceptions are mitochondria, archaebacteria, mycoplasma, some yeast)
unambiguous1 codon = 1 AA
degenerate/redundantmore than 1 codon may = same AA
non-overlappingcontinuous sequence of bases
universalgenetic code is conserved throughout evolution (exceptions are mitochondria, archaebacteria, mycoplasma, some yeast)
Silent mutationsame AA results, often the 3rd base in codon is changed (tRNA wobble)
Most dangerous mutationsframeshift>nonsense>missense>silent
Missense vs nonsense mutationchanged aa (conservative because new AA is similar in structure) vs. stop codon is created in nonsenses mutation
Frame shiftchange --> misread nucleotides downstream --> nonfunctional protein (# of BP's deleted are not a multiple of 3)

DNA Replication & Repair

Question Answer
origin of replication in prokaryotes versus eukaryotessingle prokaryotes and multiple in eukaryotes
helicaseunwinds DNA template at replication fork
single-stranding binding proteinsprevents strands from reannealing
DNA topoisomerasecreates a single or double stranded break in the helix to add or remove supercoils
primasemakes an RNA primer on which DNA polymerase III can initiate replication (prokaryotic only)
DNA polymerase IIIprokaryotic only. Elongates leading and lagging strand
DNA polymerase Iprokaryotic only. Degrades RNA primer, replaces it with DNA
DNA ligasejoins Okazaki fragments
telomeraseRNA dependent DNA polymerase that adds DNA to 3' end of chromsomes to avoid loss of DNA material in eukaryotes only
DNA polymerase alphamakes own primer. Builds Okazaki fragments on lagging strand.
DNA polymerase deltabuilds leading strand.
DNA polymerase betaDNA repair (base excision)
DNA polymerase gammareplicates mitochondrial DNA
transitionpurine to purine or pyrimidine to pyrimidine
tranversionpurine to pyrimidine or pyrimidine to purine
nucleotide excision repairrepairs bulky helix distorting lesions. Endonucleases release oligonucleotides containing damaged bases; DNA polymerase and ligase fill and reseal the gap; repairs bulky-helix distorting lesions.
base excision repairglycosylases remove the altered base and create AP site. Nucleotides are removed by endonuclease. DNA polymerase B fills the gap. Remember beta (base excision repair)
mismatch repairnewly synthesized strand's mismatched nucleotides are removed.
HNPCCmismatch repair defect
Xeroderma pigmentosumnucleotide excision repair defect; cannot repair pyrimidine dimers which are created by UV light
replicates lagging strand in eukaryotesDNA polymerase alpha
synthesizes RNA primerDNA polymerase alpha
replicates mitochondrial DNADNA polymerase gamma
replicated leading strand DNADNA polymerase delta

Transcription = DNA --> RNA

Question Answer
Protein synthesis directionN-->C
rRNAmost abundant and is made by RNA poly 1
mRNAlongest and made by RNA poly 2; carries sequence info from DNA to ribosome to be translated (massive) = capped, tailed, & spliced transcript
tRNAsmallest and made by RNA poly 3; carries A.A. to ribosome for protein synthesis (tiny)
prokaryotic RNA polymerase1 RNA polymerase, inhibited by rifampin
location of synthesis rRNAnucleolus
location of mRNA synthesisnucleoplasm
location of tRNA synthesisnucleoplasm
Start codonsAUG
euk = methionine
prok = f-Met
Stop codonsU Go Away, U Are Away, U Are Gone = UGA, UAA, UAG
Promoter regionRNA poly and other TFs bind to DNA upstream from gene locus, has AT-rich sequence and TATA box
Enhancer vs silencer regionsalters gene expression by binding TFs vs site where negative regulators or repressors bind, both can be close/far/in gene whose expression it regulates
alpha amanitininhibits RNA poly 2 and can cause liver failure if ingested, found in death cap mushrooms
RNA poly in proks vs euksprok = only 1 which makes all 3 kinds of RNA
euks - there are 3 (1- rRNA, 2- mRNA, 3- tRNA), RNA poly has no proofreading function in euks but can initiate chains
RNA processingonly in euks, occurs in nucleus after transcription, capping on 5' end with 7 methylguanosine, poly A tail on 3' end (doesn't require template), spliced out introns. This is all referring to mRNA
pre-mRNAheterogenous nuclear RNA (hnRNA) destined for translation
Splicing of pre-mRNA1. primary transcript combines with snRNPs and other proteins to make spliceosome
2. lariate-shaped (loop) intermediate is made
3. lariat is released to remove intron precisely and join 2 exons
TATA boxpromoter region that binds transcription factors and RNA polymerase II during intiation of transcription. It is located approximately 25 bases upstream from the coding region
CAAT boxanother promoter region that is located 60 to 80 bases upstream of the begining of the coding region


Question Answer
tRNA wobbleaccurate base pairing for first 2 NTs of codon so 3rd wobble position may code for same tRNA/aa (degenerate code)
tRNA structuresecondary structure, cloverleaf, antidcodon end is opposite 3' aminoacyl end, 3' end contains CCA which Can Carry A.A.
tRNA chargingaminoacyl-tRNA synthase scrutinizes aa before/after it binds to tRNA, requires ATP, if incorrect then bond is hydrolyzed
Total E expenditure for translation4 phosphoanhydride bonds (1 ATP-->AMP, 2 GTP-->GDP)
Initiation of translationactivated by GTP hydrolysis, initiation factors help assemble 40s ribosomal subunit with initiator tRNA
Eukaryote vs prokaryote ribosome subunits40S+60S-->80S (Eukaryotes even), 30S+50S-->70S (prOkaryotes odd)
Elongation in translationGoing "APE"
1. A site = incoming aminoacyl tRNA binds to A site (except for the first tRNA carrying methionine)
2. P site = accommodates growing Peptide - rRNA catalyzes peptide bond formation --> transfers growing polypeptide to A.A. in A site
3. E site = holds Empty tRNA as it Exits - ribosome advances 3 nucleotides toward 3' end of RNA moving peptidyl RNA to P site = translocation
Antibiotics that block prokaryotic ribosomeBuy AT 30 CCELL AT 50. aminoglycosides, tetracyclines, clindamycin, choraphenicol, erythromycin (macrolides), linezolid, lineomycin

Hereditary Defects in Sugar Metabolism

Question Answer Column 3
Pyruvate Kinase deficiencyinability to maintain Na/K/ATPasehemolytic anemia and jaundice that begin at birth
Pyruvate Dehydrogenase Deficiencyincrease in pyruvate with concomitant increase in lactic acid and alanine (by transamination); decrease in production of acetyl CoA: severe reduction in ATP productionlactic acidosis
Galactokinase deficiencyincrease in galactose and galacitolcataracts
Galactosemiadeficiency in GALT leading to an increase in galactose (blood, urine), galactose 1-phosphate (very toxic) and galacitol (sugar alcohol)cirrhosis, mental retardation, cataracts, galactosuria
Essential Fructosuriadeficiency of fructokinasebenign condition marked by fructosuria
Hereditary fructose intolerancedeficiency of aldolase B, increase in fructose and fructose-1-phosphatetoxic liver damage, renal disease
G6PD deficiencyinadequate NADPH production resulting in reduction of glutathione in mature RBCshemolytic anemia often induced by infections, drugs and fava beans
Acquired Pyruvate Dehydrogenase deficiencyB1 Thiamine Deficiency (Alcoholics)
Arsenic poison (garlic breath)
How do you treat Pyruvate Dehydrogenase deficiency?Vitamin Supplementation
High fat diet
Ketogenic aa's (lysine and leucine)

Glycogen Storage Diseases (all autosomal recessive)

Question Answer
What enzyme is deficient in Von Gierke (I)Glucose 6-phosphatase (liver and kidney)
Fasting hypoglycemia+ketosis+hyperlipidemia+lactic acidosis+hepatosplenomegalyVon Gierke
What enzyme is deficient in Pompe (II)alpha-1,4-glucosidase (lysosomes)
metnal retardation, hypotonia cardiomegaly, death by age 2)Infantile Pompe
Respiratory depression less severe than infantileAdult Pompe
What enzyme is deficient in Cori (III)Debranching enzyme 1,6 glucosidase in muscle and liver
Mild hypoglycemia hepatomegaly (but normal lactate and uric acid)Cori disease (less serve form of Von Gierke)
What enzyme is deficient in McArdle's (V)muscle glycogen phosphorylase
Muscle cramping, fatigue and myoglobinura or rhabdomyolysis with exerciseMcArdle Disease


Question Answer
GlycolysisPFK-1: F6P → F1,6BP
GluconeogenesisFructose 1,6 biphosphatase: F1,6BP → F6P
Glycogen synthesisGlycogen Synthase: UDP-glucose →Glycogen
GlycogenolysisGlycogen phosphorylase: alpha 1,4 glycogen linkage → Glucose-1-Phosphate
TCA cycleIsocitrate dehydrogenase
HMP shuntGlucose-6-Phosphate Dehydrogenase (G6PD)
De novo pyrimidine synthesisCarbamoyl phosphate synthetase II (CPS-II)
De novo purine synthesisGlutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
Urea cycleCarbamoyl phosphate synthetase I (CPS-1)
Carbohydrate digestionOligosaccharide hydrolase
Fatty acid synthesisAcetyl Co A Carboxylase
Beta oxidation (breakdown) of fatty acidsCarnitine Transferase
Ketone body synthesisHMG-CoA Synthase
Cholesterol synthesisHMG CoA Reductase

Amino acids

Question Answer
Tryptophan is the precursor ofSerotonin
Methionine is the precursor ofCysteine
Histidine is the precursor of Histamine
Glutamic acid is the precursor for GABA
Tyrosine is the precursor forThyroxine