RBC and cancer metabolism

Question 1

what will be observed in the serum following intravascular hemolysis?

Answer 1

hemoglobinuria

Question 2

what will be observed in the serum following extravascular hemolysis (spleen)?

Answer 2

bilirubin (jaundice) - Hb has already been dealt with by macrophages

Question 3

what is accomplished by RBC metabolism?

Answer 3

1. keeping iron reduced (2+)
2. maintaining K/Ca gradients
3. keeping protein SH groups reduced
4. maintaining cell shape

Question 4

what is the relationship between NADH and MetHb?

Answer 4

NADH transfers electrons to MetHb to replenish the 2+ state

Question 5

what is the role of ATP in maintenance of K/Ca gradients?

Answer 5

maintenance of ions across membrane

Question 6

how do RBCs keep protein thiol groups reduced?

Answer 6

transfer electrons from glutathione to thiol groups to keep them reduced

Question 7

where does glutathione get the electrons for reduction of thiol groups?

Answer 7

NADPH

Question 8

what is the result of RBC metabolism failure?

Answer 8

1. cells fill with Ca2+
2. cells release K+
3. lose biconcave shape

Question 9

what is the substrate that RBCs use for the PPP?

Answer 9

glucose-6-P

Question 10

the RBC energy clutch bypasses which step of RBC metabolism?

Answer 10

phosphglycerokinase step converting 1,3-BPG to 3-phosphoglycerate

Question 11

what is the result / purpose of the RBC energy clutch?

Answer 11

1. no consumption of ADP
2. net gain of ATP is zero

(saves one ADP expenditure and one ATP production per cycle)

Question 12

in what circumstances is the energy clutch useful for RBC metabolism?

Answer 12

if cell is full of ATP but there is no ADP and you still need to make NADH

Question 13

what regulates the energy clutch?

Answer 13

pH - lower pH increases activity - more NADH production

Question 14

what are the two enzymes that compete for 1,3-BPG?

Answer 14

1. phosphoglycerate kinase

2. diphosphoglyceromutase

Question 15

what are the regulated steps of glycolysis in RBCs?

Answer 15

1. hexokinase (glucose to glucose-6-P)

2. PFK1 (fructose-6-P to fructose-1,6-BP)

Question 16

how do acidic pH levels impact glycolysis?

Answer 16

inhibition (less lactic acid production)

Question 17

how is 2,3-BPG affected by low pH?

Answer 17

decreased

Question 18

how is oxygen affinity affected by low pH? by what mechanism?

Answer 18

increased due to less 2,3-BPG, which is inhibited by low pH

Question 19

what is the regulated enzyme in the PPP?

Answer 19

glucose-6-P dehydrogenase

Question 20

what is the function of the PPP?

Answer 20

provide reduction equivalents in the form of NADPH

Question 21

which enzyme is upregulated in response to low intracellular NADPH?

Answer 21

G6PD

Question 22

what is the role of glutathione hydrolase?

Answer 22

1. keeps sulfydryl groups reduced

2. provides electrons to convert H2O2 to H2O

Question 23

what is the role of SOD?

Answer 23

converts superoxide radical to H2O2

Question 24

what is the role of glutathione peroxidase?

Answer 24

1. converts H2O2 to water

2. oxidizes GSH to GSSG

Question 25

what is the role of glutathione reductase?

Answer 25

1. GSSG to GSH | 2. NADPH to NADH

Question 26

ultimately, where do the electrons for oxidant defense come from?

Answer 26

1. glucose to NADPH via PPP and NADP | 2. from NADPH to GSSG via glutathione reductase

Question 27

what are the two causes of nonspherocytic anemia?

Answer 27

1. G6PD deficiency - lack of NADPH | 2. pyruvate kinase deficiency - lack of NADH / ATP

Question 28

bite cells are seen with what condition?

Answer 28

G6PD deficiency

Question 29

what are the components of the RBC cytoskeleton?

Answer 29

1. spectrin fibers - underlie plasma membrane | 2. transmembrane proteins - band 3, glycophorin

Question 30

how do the RBC cytoskeletal defects present?

Answer 30

hereditary spherocytosis

Question 31

what is the most common RBC cytoskeleton defect?

Answer 31

ankyrin