Biological Chemistry Exam 1 Part 2

salt bridge

hydrogen bonding and ionic bonding

what is the greatest genetic risk factor of Alzheimer’s disease

ApoE4 (E2, E3, E4)

who created a 3D structure from precise amino acid sequence

Christian Anfinsen

how did Christian Anfinsen degrade RNA

a solution containing urea or guanidinium chloride (destroy non covalent) and B-mercaptoethanol (destroy disulfide bonds)

what interactions between amino acids determine it’s tertiary structure

salt bridges, hydrogen bonds, disulfide bonds, hydrophobic interaction

what does proper folding of bovine ribonuclease require

four disulfide bonds (8 cysteines)

what happened in Anfinsen’s experiment when the urea and B-ME were removed

denatured enzyme slowly regains activity

what happens in Anfinsen’s experiment if the urea is not removed

activity extremely low; favorable noncovalent interactions are prevented and all possible combinations are possible including 104 that are not enzymatically active

hemoglobin

oxygen from lungs to rest of the body - 4 binding sites

hemoglobin properties

allosteric protein that is cooperative in oxygen binding and release

myoglobin properties

binds oxygen in muscle cells; not cooperative (only one binding site)

what is oxygen measured as a function of

partial pressure of oxygen

myoglobin vs hemoglobin size

17.8 kd vs 66 kd

what is the only animal that lacks red blood cells containing hemoglobin

antartic blackfin icefish

Fe-protoporphyrin

heme group

heme group

Fe with 4 N (has 6 binding spots)

Fe2+ vs Fe3+ (superoxide ion)

ferrous, reduced (better state) vs ferric, oxidized (don’t want)

what is the function of the globin (why not just heme without the globin in Mb or Hb)

globin prevents oxidation (oxidized will not bind O2)

what does oxygen binding do to the iron

changes the position of the iron ion

what are the fifth and sixth binding positions on the Fe atom

proximal his (5th) and distal his (6th - stabilize bound oxygen)

2 reasons oxygen be released only in the O2 state (Fe2+)

superoxide (Fe3+) is very reactive and can quickly bind and harm other molecules; iron would be left ferric (Fe3+) state preventing further oxygen binding - metmyoglobin

what feature helps prevent superoxide release

distal his that donates hydrogen bond to bound oxygen molecule

fMRI

shows oxygen use in areas of brain

T state

taut; not binding O2 (low affinity for oxygen) - salt bridges present

R state

relaxed; bind O2 (high affinity for oxygen) - salt bridges not present

salt bridges in T state

6 between same subunits, 4 involving the C- or N- terminus

myoglobin vs hemoglobin oxygen affinity

myoglobin has higher oxygen affinity

what does a higher P50 value mean

lower binding affinity level

the Bohr effect

carbon dioxide and H+ enhance oxygen release by Hb

would a lower or higher pH have more oxygen offload

lower pH

what happens with ionic bonds at a lower pH

ionic bonds form that stabilize the T state

carbon dioxide equation to bicarbonate

CO2 → CO2 + H2O → H2CO3 → HCO3- + H+

what does the muscles release of CO2 release

H+; decreases the pH

what 3 amino acids form 2 salt bridges that stabilize the T quaternary structure

his, lys, asp

what is the role of 2,3-BPG

binds to pocket in hemoglobin that only exists in T state

what does 2,3-BPG do when bound in the pocket

stabilizes the T state and facilitates the release of oxygen

2,3-BPG (biphosphoglycerate) characteristics

highly negatively charged

how does 2,3-BPG bind to the T state

binds central cavity of deoxyhemoglobin - interacts with 3 positively charged groups on each B chain

fetal hemoglobin

must bind oxygen at same pO2 at which the mother’s hemoglobin is releasing oxygen

what is different in a fetal hemoglobin

B chain replaced with a Y chain; does not bind 2,3-BPG; HbF (pocket) His is replaced by Ser (fewer + charges)

homotrophic interactions

cooperativity of oxygen binding; substrate = regulator

heterotrophic interactions

different ligands

what is responsible for allosterism

conformational changes in quaternary structure

sickle cell disease

mutation resulting in the substitution of valine (hydrophobic) for glutamate (hydrophillic)

when is sickle cell fatal

both alleles of the B chain are mutated

what does the sickle cell trait offer protection to

malaria

how does sickle cell spread

aggregation of mutated deoxyhemoglobin molecules

CASGEVY

first treatment using gene editing