Flashcards in EXAM #1: RBC & CANCER METABOLISM Deck (47)
Do RBCs contain mitochondria and nuclei?
Do RBCs have the ability to synthesize proteins?
Can RBCs synthesize proteins to replace damaged molecules? Why or why not?
RBCs do not contain nuclei; therefore, they cannot produce proteins.
What type of RBCs are trapped in the spleen? What causes to be phagocytosed by the spleen?
- Inelastic RBCs do not retain the flexibility needed to circulate through the spleen
- Consequently, splenic macrophages phagocytose these RBCs
Older RBCs have a cytoskeletin that degenerates and loses its elasticity making them inflexible.
What is extravascular hemolysis? What is the key biochemical marker for extravascular hemolysis? What is the key clinical marker for extravascular hemolysis?
Extravascular= outside of the circulation; splenic macrophages phagocytose of RBCs
- Biochemical= bilirubin/ jaundice
- Clinical= splenomegaly
In contrast to extravascular hemolysis, what is intravascular hemolysis? What is the key biochemical marker of intravascular hemolysis?
- Mechanical disruption of RBCs IN THE CIRCULATION
- Biochemical= HEMOGLOBIN from destroyed RBCs/ hemoglobinuria
What is the difference between spherocytic anemia and non-spherocytic anemia?
Spherocytic= defect in RBC cytoskeleton leaves the cell rounded w/ diminished volume and potential for lysis
- Leads to EXTRAVASCULAR HEMOLYSIS
Non-spherocytic= enzymatic/ non-cytoskeletal cause of anemia
- Leads to both INTRA AND EXTRA-VASCULAR HEMOLYSIS
What are the four major purposes of RBC metabolism?
1) Keeping iron reduced (Fe++ vs. Fe+++)
2) Maintaining K+/ Ca++ gradients
3) Keeping protein SH-groups reduced (vs. oxidized by ROS)
4) Maintaining cell shape
What is required to keep iron reduced?
(NADH methoglobin reductase)
What is required to maintain the K+/Ca++ gradient in RBCs?
ATP i.e. ATPases
What is required to keep protein SH-groups reduced in RBCs?
What is required to maintain RBC cell shape?
What happens if RBC metabolism fails?
1) Fills with Ca++
2) Release K+
3) Lose bicocave shape
These cells will be taken up by the spleen b/c the spherical shaped cannot pass through resulting in extravascular hemolysis.
RBCs do NOT contain mitochondria; thus, what type of metabolism CANNOT happen?
1) Fatty acid oxidation
2) Aerobic metabolism
BOTH require mitochondria
What metabolic pathways CAN occur in RBCs?
1) Glyocolysis (anaerobic)
What are the regulated steps of glycolysis in RBCs? What regulates these two enzymes?
****In contrast to other cells, glucose is NOT the regulator of glycolysis in RBCs; rather pH is. A DECREASE in pH will STOP glycolysis in RBCs.*****
When the RBC is full on ATP but needs NADH, how does the cell make NADH?
"Energy clutch" i.e. perform glycolysis without gain of ATP
Draw the pathway of ATP, NADH, and NADPH generation in RBCs.
What is the crucial step of the "energy clutch?"
1) 1,3 bisphosphoglycerate -->2,3 bisphosphoglycerate
2) 2,3 bisphosphoglycerate is dephosphorylated to 3-hosphoglycerate
3) 3-phosphoglycerate re-enters glycolysis WITHOUT net production of ATP
What metabolic pathway generates NADPH?
What happens to the "energy clutch" at low pH?
Recall, glycolysis STOPs at LOW pH; therefore,
*2,3 BPG production STOPs at LOW pH*
When pH is low and there is abundant lactate, what will RBCs do?
Oxidize/ consume lactate to obtain NADH for the defense of Hb
This returns the pH to normal.
What enzyme conversts 1,3 bisphosphoglycerate converted into 2,3 bisphosphoglycerate?
What effect does 2,3 BPG have on Hb's affinity for oxygen?
2,3 BPG DECREASES Hb's affinity for oxygen
What happens to 2,3 BPG at low pH?
Synthesis is INHIBITED
What is the effect less 2,3 BPG production acidic conditions?
Increased Hb/RBC oxygen affinity/saturation
*****Thus, acidosis INCREASES the oxygen saturation of the blood. However, the BOHR EFFECT DECREASES oxygen saturation in acidic conditions. This gives the RBC a higher oxygen affinity in the lungs b/c of the effects of 2,3 BPG and a lower oxygen affinity in the tissue b/c of the Bohr effect, which facilitates oxygen unloading to hypoxic tissues.*****
What is the"gate-keeper" enzyme of the PPP?
Glucose-6 phosphate dehydrogenase
What activates Glucose 6-phosphate dehydrogenase?
What is the role of NADPH in RBCs?
This is also the reduction equivalent needed for biosynthesis.