glycolysis in RBCs

Question 1

under the aerobic condition ( presence of mitochondria & O2 ) :
-the total ATP produced are ……. ( payoff phase ) energy generation phase ,
-there’s ……..lost ( preparatory phase ) energy investment phase ,
-so net ATP gain is ……

Answer 1

10 molecules
2 ATP
8 molecules

Question 2

illustrate sources of 10 ATP

Answer 2

1. substrate level phosphorylation (4 ATP) :
   - production of ATP directly without respiratory chain by converting ADP to ATP
   - 2ATP by phosphoglyceric kinase enzyme
   - 2ATP by pyruvate kinase enzyme
2. oxidative phosphorylation ( 6ATP) :
   - 2 NADH+H are produced by glycerdhyde 3 -P dehydrogenase enzyme
   - this 2 NADH+H will give 6 ATP through respiratory chain in mitochondria & O2

Question 3

under anaerobic conditions ( absent of mitochondria & O2 ) :
total ATP produces are ……
……. lost ( preparatory phase )
net ATP gain is …….

Answer 3

4 ATP
2ATP
2 molecules

Question 4

list example for anaerobic glycolysis ( hypoxic conditions )

Answer 4

1. tissue with dec O2 tension :
   - muscle cell during sever exercise “ NADH exceed the oxidative capacity of the respiratory chain , so pyruvate convert to lactate , dec PH & cramps )
2. tissue with lack mitochondria :
   -RBCs ( no mitochondria)
   - cornea, eye lens , retina , testes, white muscle fiber , renal medulla , WBCs ( poor mitochondria )

Question 5

illustrate the end of anaerobic glycolysis

Answer 5

lactate released to circulation to :
1. liver : by gluconeogenesis , lactic acid converted to glucose
2. heart : by reversal of lactate dehydrogenase enzyme , lactic acid convert to pyruvate to utilized in cardiac tissue by TCA cycle

Question 6

list fate of the products of glycolysis

Answer 6

• 2ATP
  -2pyruvic
  -2 NADH+H convert to NAD+

Question 7

illustrate the fate of NADH+H under aerobic condition

Answer 7

• used for energy production at mitochondria via respiratory chain
• NADH+H are carried to inside of mitochondria by malate aspartate and glycerol 3 -P substrate shuttles because inner mitochondrial membrane is impermeable to NAD+

Question 8

what’s the importance of glycolysis in RBCs ? (RBCs metabolism)

Answer 8

1. energy production (2ATP)
2. 2,3 BPG shunt in RBCs (synthesis of 2,3 bis-P glycerate)

Question 9

……. only source for energy in RBCs because there is ……..

Answer 9

glycolysis
no mitochondria

Question 10

glycolysis is only ……, so the end product of glycolysis in RBCs is always ……& produce only …..

Answer 10

anaerobic
lactic acid
2 ATP

Question 11

the P-glycerate kinase reaction is by passed , loss of …… during ……of one molecule glucose

Answer 11

2ATP
oxidation

Question 12

illustrate the effect of 2,3 bis phosphoglycerate on O2 affinity of Hb

Answer 12

1. bind to beta chain of Hb & dec O2 affinity of Hb
2. enable Hb to release O2 to tissue

Question 13

illustrate the 2,3 BPG shunt in RBCs ( Rapoport - lubering cycle )

Answer 13

in RBCs, instead of two 1,3 bis phosphoglycerate production , only one 1,3 bis phosphoglycerate & 2,3 bis phosphoglycerate is formed by bis phosphoglycerate mutase

Question 14

in that reaction …….. is lost .
discuss the reason

Answer 14

-2 ATP
- 2,3 BPG dissociate to 3PG and Pi without generation of ATP

Question 15

in ……. , may be two 2,3 bis phsphoglycerate are formed

Answer 15

sever hypoxia

Question 16

rate limiting step of glycolysis is …….

Answer 16

PFK1

Question 17

illustrate the regulation of glycolysis

Answer 17

1. hexokinase :
   -inhibited by glucose 6-P
2. phosphofructo kinase 1(PFK1) :
   -stimulated by inc AMP & fructose 2,6 bis P
   - inhibited by inc ATP & citrate “ match glycolysis and kreb’s cycle “
3. pyruvate kinase :
   - feed forward stimulation by fructose 1,6 bis P
   - inhibited by inc ATP

Question 18

what’s the cause of pyruvate kinase deficiency ?

Answer 18

inherited defective gene “ congenital “

Question 19

illustrate the pathology of pyruvate kinase deficiency.

Answer 19

1. reduces 2 ATP produced from glycolysis
2. the net ATP gain will be zero
3. this lead to impaired Na+ pump
4. potassium leak out from RBCs
5. intracellular fluid becomes hypotonic
6. water move down its conc gradient out of the cell
7. the cells shrinks and phagocytosed by MQ of the spleen cause hemolytic anemia
8. the symptoms can be compansated by high level of 2,3 BPG which inc delivery of O2 to the cells
9. heterozygote patient resist malaria
10. liver cell not affected (why)
    have mitochondria & can generate ATP by oxidative phosphorylation

Question 20

list ttt of pyruvate kinase deficiency

Answer 20

transfution of packed RBCs

Question 21

what’s the clinical picture of pyruvate kinase deficiency ?

Answer 21

• non spherocytic hemolytic anemia
• jaundice