Final Review Block 1 Flashcards
blood buffering equation
CO2 + H20 –> H2CO3 –> HCO3- + H+
influence of water on protein folding
proteins will fold to minimize unfavorable interactions- will have charged/hydrophilic groups externally and hydrophobic groups internally
hydrophobic amino acids (8)
valine- Val, V alanine- Ala, A leucine- Leu, L isoleucine- Ile, I tryptophan- Trp, W tyrosine- Tyr, Y phenylalanine- Phe, F methionine- Met, M
Basic amino acids (3)
Histidine- His, H
Lysine- Lys, K
Arginine- Arg, R
Acidic Amino Acids (2)
glutamate- Glu, E
Aspartate- Asp, D
Polar amino acids (4)
serine- Ser, S
threonine- The, T
asparagine- Asn, N
glutamine- Gln, Q
Special amino acids (3)
cysteine- Csy, S
proline- Pro, P
glycine- Gly, G
special feature of Histidine
pKa is very close to physiologic pH
special feature of cysteine
can make disulfide bonds
special feature of proline
rigid structure d/t presence of ring
special feature of glycine
smallest R group (H)
special feature of Trp, Phe, Tyr
contain aromatic rings
Phe is the largest
special feature of serine and threonine
can be phosphorylated
what is the HH equation?
pH = pKa + log [A-]/log[HA]
what are the normal values for pka, pH, [CO2], [HCO3]
pka = 6.1 pH = 7.35-7.45 [CO2] = 1.2 mM [HCO3] = 24 mM
what is the ultimate determinant of final protein structure?
primary structure (linear polypeptide sequence)
describe peptide bonds
bonds between individual aa, rigid and do not allow for rotation
describe a-helix
each COO- is H-bonded to H that is 3.6 aa residues away
what disrupts a-helix?
proline rigid ring structure
b-sandwich? b- turns?
b-sandwich: interaction between the internal hydrophobic surfaces of 2 b-sheets
b-turns: 4 aa that form a sharp bend to reverse the direction, proline is good bc of built-in bend, glycine good bc of its small size
describe coiled-coil, example?
interaction of hydrophobic residues on 2 adjacent a-helices, ex is leucine zipper, commonly seen in transcription factors
describe zinc finger, example?
cys and his residues bind Zn, also seen in transcription factors with Zn binding DNA
what are peptidyl propyl cis-trans isomerases?
enzymes that facilitate the conversion of proline residues from trans to cis configuration
what are protein disulfide isomerases?
enzymes that catalyze formation of disulfide bonds
what are the chaperone proteins?
molecular chaperones (Hsp70) chaperonins (GroEL-GroES)
describe the function of Hsp70
molecular chaperone, prevents denaturation during fever by binding to exposed hydrophobic residues and preventing aggregation, use ATP
describe the function of GroEL-GroES
chaperonin, forms hydrophilic folding chamber that sequesters unfolded proteins and allows them to fold properly, uses ATP
describe collagen structure
Gly-Pro-X motif, proline can be hydroxylated allowing for the formation of cross-bridges and increased stability. normal collagen = two a-1 and one a-2
describe OI (severe and mild mutation)
autosomal dominant
severe- missense mut for glycine, results in normal amount of abnormal collagen (not able to fold properly)
mild- loss of 1 a-1 allele, leads to small quantities of normal collagen
describe survy
results from ascorbic acid def – ascorbic acid is a cofactor for proline hydroxylation, in the absence of ascorbic acid, cross linkages cannot form and collagen in weaker
describe protein-ligand specificity
shape of the binding site is compatible to the ligand to allow for multiple covalent interactions (hand in glove vs. induced fit)
what is the typical purpose of farnesylation/myristylation?
addition of fatty acid to anchor protein to a membrane
3 types of chromatography
size- smaller molecules go through pores in beads, larger molecules move through faster
ion exchange- (+) proteins bind (-) beads and uncharged or (-) proteins move through after, (+) removed with salt
affinity
what is a “cation exchange column”?
lined with (-) charges
describe western blot
used to eval proteins (1-2) uses antibody probe
describe SDS-PAGE
proteins denatured/linearized by SDS
SDS gives surface negative charge
will separate based on molecular wt
smaller particles will move faster/farther
describe 2D gel electrophoresis
separation based on size and charge
can be useful for assessing level of phosphorylation, can be used for larger protein volume (100s)
describe mass spectrometry
can be used for 1000s, provides info for identification
why is the active site of an enzyme usually located in a cavity?
to restrict access of water to area– water can disrupt ligand binding
what are the ways in which enzymes decrease activation energy? (3)
- orient molecules favorably
- separate charge to favor a reaction
- strain a substance toward transition state
what is the role of His in hemoglobin?
binds to iron and prevents it from oxidizing
what happens if iron in heme oxidizes?
methmegolbinemia
what is the hill coefficient?
measure of cooperativity
what are the 2 states of hemoglobin?
R state- high O2 affinity
T- state- low O2 affinity
how is hemoglobin transitioned from T to R?
when 1st O2 binds, iron will move into plane and pull His with it, when His moves it causes a conformation change that leads to the subunit in the ab pair moving, this enhances hemoglobin’s ability to bind O2
what is BPG?
intermediate of glycolysis
binds to T state and stabilizes it
what is the Bohr effect?
increased H+ = increased CO2, when CO2 is increased, hemoglobin will have decreased affinity for O2 and it will be released into tissues (T state His 146 is Hbonded to Asp94)
oxygen dissociation curve
right shit- decreased affinity for O2 = more released into tissues = T state
left shift- increased affinity for )2 = less released into tissues = R state
what conditions favor R-state?
hold onto O2:
High O2
decreased CO2
decreased BPG
what conditions favor T-state?
release O2:
low O2
high CO2
high BPG
what would hemoglobin want to give up O2 if BPG is high?
BPG is an intermediate of glycolysis, thus if increased glycolysis is occurring, this is an indication that tissues need O2, so BPG stabilizes hemoglobin T state so that it can release O2 into tissues for OXPHOS
what is the effect of fetal hgb on the curve?
fetal hemoglobin has a higher affinity for O2, causes a left shift
what is the basis for base pairing?
chargaff’s rules AT, CG
SLE
autoantibodies to DNA, leads to inflammation, tissue injury, organ dysfunction
what is RNA more easily degraded that DNA
presence of 2’OH leaves RNA more susceptible to hydrolysis
most abundant type of RNA
rRNA (80%)
what is the usual “form” for monosaccharides? what can alter it?
usually D form, with OH on the right
can be altered with epimerases
what type of polysaccharide cannot be digested by humans?
cellulose b(1,4)
what are GAGs?
sugars with repeating units of disaccharides
what aa form O-linked sugars?
serine, threonine
what aa forms N-linked sugars?
asparagine
what is the double bond configuration for almost all biologic systems?
cis
what FA are prominent on the outer leaflet? inner?
outer- phos-choline, sphingomyelin, glycolipids
inner- phos-serine, phos- linositol
what are flippases? floppases?
flippases- enzymes that move phos-serine from outer to inner against gradient
floppases- move phos-choline and sphingolipids from inner to outer against gradient
where are the membrane components synthesized?
phospholipids- ER
glycolipids- ER, golgi
cholesterol- in membranes of ER
what will decrease membrane fluidity?
increased cholesterol, increased length of FA tails, lipid rafts
what will increase membrane fluidity?
increased polyunsaturated fats
what causes sickle cell anemia?
AR, glu-val at 6th position of b subunit of hgb
when does sickling occur?
any situation that decreased O2, will lead to polymerization of hgb via hydrophobic interactions
what tests are done for sickle cell?
NBS- cation exchange column chromatography, isoelectric focusing
what is the main source of pain in SCA?
vaso-occlusion in post-capillary venules
1 cause of death in pts with SCA
acute chest syndrome
what reduces the risk of CVA?
transfusion
how does hydroxyurea treat SCA?
increases fetal hgb levels
