Flashcards in RBC and cancer metabolism Deck (31)
what will be observed in the serum following intravascular hemolysis?
what will be observed in the serum following extravascular hemolysis (spleen)?
bilirubin (jaundice) - Hb has already been dealt with by macrophages
what is accomplished by RBC metabolism?
1. keeping iron reduced (2+)
2. maintaining K/Ca gradients
3. keeping protein SH groups reduced
4. maintaining cell shape
what is the relationship between NADH and MetHb?
NADH transfers electrons to MetHb to replenish the 2+ state
what is the role of ATP in maintenance of K/Ca gradients?
maintenance of ions across membrane
how do RBCs keep protein thiol groups reduced?
transfer electrons from glutathione to thiol groups to keep them reduced
where does glutathione get the electrons for reduction of thiol groups?
what is the result of RBC metabolism failure?
1. cells fill with Ca2+
2. cells release K+
3. lose biconcave shape
what is the substrate that RBCs use for the PPP?
the RBC energy clutch bypasses which step of RBC metabolism?
phosphglycerokinase step converting 1,3-BPG to 3-phosphoglycerate
what is the result / purpose of the RBC energy clutch?
1. no consumption of ADP
2. net gain of ATP is zero
(saves one ADP expenditure and one ATP production per cycle)
in what circumstances is the energy clutch useful for RBC metabolism?
if cell is full of ATP but there is no ADP and you still need to make NADH
what regulates the energy clutch?
pH - lower pH increases activity - more NADH production
what are the two enzymes that compete for 1,3-BPG?
1. phosphoglycerate kinase
what are the regulated steps of glycolysis in RBCs?
1. hexokinase (glucose to glucose-6-P)
2. PFK1 (fructose-6-P to fructose-1,6-BP)
how do acidic pH levels impact glycolysis?
inhibition (less lactic acid production)
how is 2,3-BPG affected by low pH?
how is oxygen affinity affected by low pH? by what mechanism?
increased due to less 2,3-BPG, which is inhibited by low pH
what is the regulated enzyme in the PPP?
what is the function of the PPP?
provide reduction equivalents in the form of NADPH
which enzyme is upregulated in response to low intracellular NADPH?
what is the role of glutathione hydrolase?
1. keeps sulfydryl groups reduced
2. provides electrons to convert H2O2 to H2O
what is the role of SOD?
converts superoxide radical to H2O2
what is the role of glutathione peroxidase?
1. converts H2O2 to water
2. oxidizes GSH to GSSG
what is the role of glutathione reductase?
1. GSSG to GSH
2. NADPH to NADH
ultimately, where do the electrons for oxidant defense come from?
1. glucose to NADPH via PPP and NADP
2. from NADPH to GSSG via glutathione reductase
what are the two causes of nonspherocytic anemia?
1. G6PD deficiency - lack of NADPH
2. pyruvate kinase deficiency - lack of NADH / ATP
bite cells are seen with what condition?
what are the components of the RBC cytoskeleton?
1. spectrin fibers - underlie plasma membrane
2. transmembrane proteins - band 3, glycophorin
how do the RBC cytoskeletal defects present?