Exam 1 biochem

Question 1

Synthesis of heme starters

Answer 1

glycine and succinyl-CoA (initially)

Question 2

Heme pocket properties

Answer 2

hypdrophobic residues
mouth of pocket is polar residues
Fe2+ covalently linked to His F8

Question 3

Highly conserved residues of hemoglobin

Answer 3

prox His (F8)
distal His (E7)
glycine (B6), allows B and E helices approximation

Question 4

Fetal hemoglobin

Answer 4

has gamma instead of beta subunits

replaced starting 3 months prior to birth

Question 5

Hemoglobin gene locations

Answer 5

chromosome 11 for epislon, gamma, delta, beta

chromosome 16 for zeta and alpha

Question 6

Oxygen binding to hemoglobin

Answer 6

T state is low affinity
R state high affinity
T to R shift axis by 15 degrees
heme flattens out in R state

Question 7

Bohr effect of oxygen binding

Answer 7

decreased pH increases oxygen release
allows more release to metabolically active tissues
due to stabilization of T state with protonation (mostly His and Val residues)

Question 8

CO2 binding to hemoglobin

Answer 8

forms salt bridges
stabilizes T state
increased oxygen release

Question 9

Bisphosphoglycerate and hemoglobin

Answer 9

BPG increases oxygen release
stabilizes T state in center of Hb
oxygen binding expels BPG in center

Question 10

Fetal and maternal Hb affinities

Answer 10

Fetal Hb has lower affinity for BPG
increases oxygen binding over maternal Hb
due to Serine instead of His on 143 beta

Question 11

Hemoglobin S

Answer 11

Glu6Val mutation
sticky patch on S and T states
causes polymerization of Hb’s
sickling of cells

Question 12

Hemoglobin C

Answer 12

mild hemolytic anemia

Glu(beta6)Lys mutation

Question 13

Hemoglobin M

Answer 13

promotes metHb formation

cyanosis

Question 14

Sickle Cell disease

Answer 14

splenic sequestration
RBC depletion/anemia
pain episodes
kidney failure

Question 15

Acute sickle dactylitis

Answer 15

aka Hand/foot syndrome
swelling of hands/feet
sx in young children
tx with fluids/pain meds

Question 16

Thalaseemias types and mutations

Answer 16

alpha-deletion

beta-point mutations

Question 17

Alpha thalassemia

Answer 17

gamma 4- Hb Bart’s (fetus)
beta 4- Hb H (adult)
tetramer formation

Question 18

Polycythemia

Answer 18

decreased oxygen release

causes increased RBC production

Question 19

Glycosylated Hb

Answer 19

Glc binds Hb in high serum conc

good for monitoring diabetics (HbA1c)