Specialization Of Proteins Iii (Foundations Exam 1)

Front 1

primary purpose of blood

Back 1

deliver nutrients to tissues and eliminate metabolic by products
- amino acids are used for de-novo synthesis of proteins
- glucose and fat are used as fuel

Front 2

by products of anaerobic and aerobic metabolism

Back 2

- acids: pyruvate and lactate, CO2 --> carbonic acid (H2CO3)
- RBCs are the major source of lactic acid in the blood

Front 3

Tense (T) form of Hb

Back 3

- deoxy form of Hb
- stabilized by eight salt bridges between C-terminal residues of all four units
- iron is pulled away from the plane of the heme--> more difficult for O2 to bind
- stabilized by H+, CO2, and BPG

Front 4

Relaxed (R) form of Hb

Back 4

- oxy form of Hb
- does not have salt bridges --> binding of O2 ruptures bridges --> less stable structure
- iron is pulled by oxygen into plane --> easier for O2 to bind
- high affinity for O2
- stabilized by O2

Front 5

carbon monoxide

Back 5

- higher affinity for iron and heme than O2
- sterically hindered from binding by the position of the distal histidine on the E-helix
- binds more efficiently straight on

Front 6

cooperatively of Hb

Back 6

-when O2 binds to Hb subunit--> induces conversion from T form to R form
- O2 pulls iron atom into plane of heme -->pulls on proximal histidine --> ruptures salt links and "frees up" other subunits
- increased affinity for O2

Front 7

The binding curve

Back 7

distinct sigmoid shape of hemoglobin indicates high cooperatively
--> low affinity for O2 at a low O2 pressure (PO2)
--> increased affinity with increase in PO2
- myoglobin is a monomer and does not exhibit cooperatively
- lower the P50, the higher the affinity

Front 8

the Bohr effect

Back 8

- protons are products of metabolism
- binding of H+ induces and R to T conversion in Hb
- enhanced by lower pH ( high [H+] ) in capillaries --> lower affinity for O2
- high pH in lungs --> increased affinity for O2
- mediated by histidine (pka 6.0) protonates and forms salt bridge with aspartate
** ensures that O2 dissociates from Hb into tissues

Front 9

the CO2 effect

Back 9

- product of metabolism
- binds to Hb at N-terminus forming carbamino group
- induces formation of salt link between N-terminus and one of alpha helices
- stablilizes T form --> lower affinity for O2
- promote dissociation of O2 in capillaries

Front 10

2,3-bisphosphoglycerate (BPG)

Back 10

- produced in RBCs from metabolism of glucose (under low PO2 in peripheral tissues)
- one molecule binds to Hb, sits in cleft of T form --> decreasing affinity for O2
- necessary to maintain cooperativity of Hb otherwise would look like myoglobin curve
- mechanism for high altitude adjustment
--> increase in BPG and decrease in O2 binding affinity
--> allows Hb to readily release O2 to tissues to ensure adequate supply

Front 11

fetal hemoglobin

Back 11

- contains gamma chains instead of beta chains --> lower affinity for BPG
- HbF has a higher affinity for O2 which ensures the transfer of O2 from maternal blood to fetal circulation
- saturation curve similar to myoglobin

Front 12

passive mechanism of buffering

Back 12

- CO2 is hydrated by an erythrocyte enzyme, carbonic anhydrase, to form bicarbonate and proton
- Hb absorbs H+ at His residues and CO2 binds to N-termini of globin chains

Front 13

active mechanisms of buffering in blood

Back 13

- lungs expel CO2
- kidneys regulate HCO3- levels
--> maintain physio pH
(arterial pH 7.2-7.4; venous pH 7.0-7.2)

Front 14

Hemoglobin S (HbS)

Back 14

sickle cell anemia
- polymer chain of Hb are induced in T state by single point mutation
- non-polar Val replaces charged Glu
- Val does not interact well with water --> binds to hydrophobic pocket on an adjacent alpha subunit
- chains of deoxyhemoglobin S form in solution
- more fragile --> easily destroyed
** resistance to malaria