Genetics + Biochem

Question 1

RBC structure

Answer 1

1. Anuclear
2. Biconcave disc
3. Extremely flexible
   A. Spectrin
   B. Actin
   C. Band 4.1
   D. Band 4.2
   E. Ankyrin

Question 2

Anaerobic glycolysis in RBCs

Answer 2

1. Per glucose
   A. 2 ATP
   B. 2 NADH
   C. 2 pyruvate
2. NAD+ regenerated in lactate production
3. Lactate -> Cori cycle in liver
4. GLUT 1 transporter brings glucose into cell

Question 3

2,3 BPG production in RBCs

Answer 3

1. Allosteric regulation of O2 binding to Hb
2. Most abundant organophosphate in RBCs
3. Rapidly degraded in blood stored for transfusions
4. Inc in adapting to high altitudes
5. Binds to (+) cavity formed by beta chains of deoxynomoglobin

Question 4

HMP shunt in RBCs

Answer 4

Aka: PPP
1. Oxidative reactions -> 2 NADPH
A. 3 irreversible steps
B. Rate limiting: G6PD
2. Nonoxidative reactions
A. Reversible steps
B. Inter convert sugars w/ 3-7 Cs
C. Enzymes
1. Transaldolase
2. Transketolase
A. Required TPP (from thiamine, Vit B12) => imp for dx low thiamine (activity in RBCs measured)
D. Ribose 5-P not needed in RBCs because there is no nucleotide biosynthesis
3. Oxidative and nonoxidative rxns operate independently
4. Need of cell determine which pathway is used

Question 5

NADPH fxns

Answer 5

1. E- donor for biosynthesis 
  A. FA
  B. Cholesterol
  C. Steroids
2. E- donor for neutralization of ROS*** role in RBCs
3. Reducing equivalents for Cyt P450 system
  A. Biosynthesis steroids
  B. Detox xenobiotics
4. Role in phagocytosis
5. Substrate for NO synthesis

Question 6

Heme structure

Answer 6

1. 6 bonds to Fe3+
   A. 4 pyrrole rings
   B. 1 proximal histidine - heme group bound
   C. 1 O2 - stabilized by distal Histidine
2. 2 alpha chains
3. 2 beta chains
4. Weak ionic and hydrogen bonds between 2 alpha-beta dimers in deoxygenated state
5. Strong interactions (hydrophobic) between alpha and beta chains form stable alpha-beta dimers

Question 7

Heme biosynthesis

Answer 7

1. Bone marrow (85%)
2. Multiple steps
3. Requires iron

Question 8

Heme degradation

Answer 8

1. Mononuclear phagocyte system (MPS)
   A. Spleen
   B. Liver
   C. Bone marrow

Question 9

Myoglobin

Answer 9

1. One heme and one chain
2. Easier to saturate myoglobin => good storage molecules
3. Myoglobin higher O2 affinity than hemoglobin

Question 10

P50

Answer 10

Indicator for change in affinity of hemoglobin for O2:
1. Inc = dec in affinity (shift right)
2. Dec = inc in affinity (shift left)
3. Allosteric effectors:
  A. PO2
  B. PCO2
  C. PH changes
  D. 2,3-BPG

Question 11

Bohr effect

Answer 11

Binding H+ to Hb -> right shift
1. Co2 + H20  H2CO3  HCO3- + H+
  A. Carbonic anhydrase 
2. Dec pH -> shift right
  A. Greater pO2 required to achieve O2 saturation
3. Lungs have higher pH than tissues 
  A. O2 binds Hb
  B. CO2 released from Hb
4. Tissues
  A. O2 released
  B. CO2 binds

Question 12

2,3 BPG role in RBCs

Answer 12

1. Allosteric regulation of O2 binding to Hb
2. Binds deoxy-Hb, but not oxy-Hb
3. Hb oxygenation narrows pocket and causes 2,3-BPG release
4. Dec affinity of Hb when 2,3-BPG bound -> O2 release
5. Chronic hypoxia effect

Question 13

O2 saturation

Answer 13

1. Degree saturation not dependent on [Hb] w/in physiologic range
2. Hb content determines blood [O2]

Question 14

Carbon monoxide (CO)

Answer 14

1. Affinity CO 220x > O2
2. Binds Carboxyhemoglobin (Bright red)
3. Causes inc affinity O2
   A. Curve shifted rt.
   B. Becomes hyperbolic
4. Hemoglobin I able to release O2

Question 15

HbA1c

Answer 15

Alpha-2 beta-2 - glucose

1. Reflects amount glucose in blood
2. More consistent because Hb life span is 120 days

Question 16

O2 transport to fetus

Answer 16

1. HbF affinity O2 > HbA
2. HbF weakly binds 2,3-BPG
3. O2 -> placenta -> fetus RBCs
4. HbF affinity = HbA w/o 2,3-BPG