RBC and cancer metabolism Flashcards

1
Q

what will be observed in the serum following intravascular hemolysis?

A

hemoglobinuria

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2
Q

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

A

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

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3
Q

what is accomplished by RBC metabolism?

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

what is the relationship between NADH and MetHb?

A

NADH transfers electrons to MetHb to replenish the 2+ state

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5
Q

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

A

maintenance of ions across membrane

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6
Q

how do RBCs keep protein thiol groups reduced?

A

transfer electrons from glutathione to thiol groups to keep them reduced

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7
Q

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

A

NADPH

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8
Q

what is the result of RBC metabolism failure?

A
  1. cells fill with Ca2+
  2. cells release K+
  3. lose biconcave shape
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9
Q

what is the substrate that RBCs use for the PPP?

A

glucose-6-P

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10
Q

the RBC energy clutch bypasses which step of RBC metabolism?

A

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

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11
Q

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

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

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

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12
Q

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

A

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

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13
Q

what regulates the energy clutch?

A

pH - lower pH increases activity - more NADH production

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14
Q

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

A
  1. phosphoglycerate kinase

2. diphosphoglyceromutase

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15
Q

what are the regulated steps of glycolysis in RBCs?

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

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

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16
Q

how do acidic pH levels impact glycolysis?

A

inhibition (less lactic acid production)

17
Q

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

A

decreased

18
Q

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

A

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

19
Q

what is the regulated enzyme in the PPP?

A

glucose-6-P dehydrogenase

20
Q

what is the function of the PPP?

A

provide reduction equivalents in the form of NADPH

21
Q

which enzyme is upregulated in response to low intracellular NADPH?

A

G6PD

22
Q

what is the role of glutathione hydrolase?

A
  1. keeps sulfydryl groups reduced

2. provides electrons to convert H2O2 to H2O

23
Q

what is the role of SOD?

A

converts superoxide radical to H2O2

24
Q

what is the role of glutathione peroxidase?

A
  1. converts H2O2 to water

2. oxidizes GSH to GSSG

25
Q

what is the role of glutathione reductase?

A
  1. GSSG to GSH

2. NADPH to NADH

26
Q

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

A
  1. glucose to NADPH via PPP and NADP

2. from NADPH to GSSG via glutathione reductase

27
Q

what are the two causes of nonspherocytic anemia?

A
  1. G6PD deficiency - lack of NADPH

2. pyruvate kinase deficiency - lack of NADH / ATP

28
Q

bite cells are seen with what condition?

A

G6PD deficiency

29
Q

what are the components of the RBC cytoskeleton?

A
  1. spectrin fibers - underlie plasma membrane

2. transmembrane proteins - band 3, glycophorin

30
Q

how do the RBC cytoskeletal defects present?

A

hereditary spherocytosis

31
Q

what is the most common RBC cytoskeleton defect?

A

ankyrin