Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Scientific Foundations > Lecture 45 > Flashcards

Lecture 45 Flashcards

HMP Shunt and RBC Metabolism

1
Q

RBC function

A

transport of oxygen from lungs to tissues

pg 1176

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

RBC structure

A
  • lack nucleus and membrane-bound cellular organelles
  • shaped as a biconcave disc to maximize the cell surface for gas exchange
  • extremely flexible to pass through narrow capillaries

pg 1176

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

RBC life

A
  • short life span -> average of 120 days
  • fast turnover -> 1012 RBC produced daily

pg 1176

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

RBC metabolism overview

A
  • no mitochdondria, no ER, etc -> no fatty acids used for energy
  • glycolysis: synthesis of ATP (2 per 1 glucose), production of 2,3 BPG (bisphosphoglycerate), and reduction of Fe3+ to Fe2+ (2+ can reversibly bind to O2
  • pentose phosphate pathway (PPP) or hexose monophosphate shunt (HMP shunt): role of NADPH in RBC

pg 1177

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

anaerobic glycolysis

A
  • for 1 glucose: 2 ATP net energy yield, 2 NADH, 2 pyruvate
  • NAD+ is regenerated through lactate production (to keep glycolysis going by converting pyruvate to lactic acid)
  • lactate is sent to the liver (part of Cori cycle) for production of glucose via gluconeogenesis

pg 1179

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

GLUT 1

A
  • distribution: human erthyrocyte, blood-brain barrier, blood-retinal barrier, blood-placental barrier, blood-testis barrier
  • expressed in cell types with barrier functions
  • high-affinity glucose transport system
  • RBCs rely exclusively on glucose for energy and require this transporter

pg 1180

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

pyruvate kinase deficiency

A
  • RBCs have their own type of pyruvate kinase for use in glycolysis
  • results in hemolytic anemia (nonspherocytic)
  • symptoms: fatigue, unusually pale skin, SOB, jaundice, increased risk of gallstones

pg 1182

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

pyruvate kinase deficiency vs G6PD deficiency

A
  • G6PD deficiency most common cause of hemolytic anemia -> pyruvate kinase deficiency is 2nd most common
  • distinguish: pyruvate kinase deficiency has lack of Heinz bodies (precipitated hemoglobin)

pg 1182

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

2,3-bisphosphoglycerate (2,3-BPG)

A
  • formed from 1,3-BPG via a mutase
  • allosteric regulator of O2 binding to Hb
  • most abundant organophosphate in RBC
  • rapidly degraded in blood stored for transfusion
  • increased in adapting to high altitudes

pg 1183

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

hemoproteins

A
  • in hemoglobin (transport) and myoglobin (storage in muscle), iron must be in Fe2+ form to reversibly bind oxygen
  • cytochrome can be in either form and has function in ETC
  • cytochrome P450 can be in either form and has function in hydroxylation
  • catalase can be in either form and functions in degradation of H2O2

pg 1185

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

heme iron oxidation

A
  • hemoglobin (Fe2+) oxidized by drugs and endogenous oxidants to methemoglobin (Fe3+)
  • metHb unable to bind O2 and leads to methemoglobinemia
  • metHb reduced to Hb by NADH-cytochrome b5 reductase

pg 1186

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

methemoglobinemia

A
  • “chocolate cyanosis” -> blue coloration of the skin and mucous membranes, brown-colored blood as a result of the dark-colored metHb
  • babies have half the capacity to reduce metHb

pg 1186

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

methemoglobinemia symptoms and treatment

A

Symptoms

  • related to degree of tissue hypoxia
  • anxiety, headache, and dyspnea
  • rarely -> coma and death when metHb is more than 70%

Treatments

  • methylene blue (a reducing agent) -> reduces metHb back to Hb and shows results within minutes

pg 1186

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

acquired methemoglobinemia

A
  • oxidative stress
  • certain drugs and/or their metabolites causing inability to maintain iron in its Fe2+ state

pg 1187

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

congenital methemoglobinemia

A
  • deficiency of NADH-cytochrome b5 reductase
  • mutations in the α- or β- globin chain producing abnormal HbM resistant to the reductase (rare)

pg 1187

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

deficiency of NADH-cytochrome b5 reductase

A
  • autosomal recessive disorder
  • close relative mating
  • makes skin very blue, but no other clinical presentation
  • “Kentucky Blue People”

pg 1188

17
Q

HMP shunt

A

hexose monophosphate shunt

pg 1190

18
Q

HMP shunt oxidative reactions

A
  • 3 irreversible steps -> produces NADPH
  • rate-limiting committed step: glucose 6-phosphate dehydrogenase (G6PD)
  • inhibitors: NADPH (competitively)
  • activators: insulin stimulates G6PD expression (signal of high nutrient state)

pg 1190

19
Q

HMP shunt nonoxidative reactions

A
  • results in ribose 5-phosphate
  • reversible steps
  • interconvert sugars with 3 to 7 carbons
  • enzymes: transaldolase and transketolase

pg 1191

20
Q

transketolase

A
  • requires TPP (from thiamine, vit. B1)
  • important in diagnosis of thiamine deficiency
  • done by measurement of its activity in RBCs

pg 1191

21
Q

HMP shunt direction

A
  • determined based on the cellular need
  • oxidative and non-oxidative can occur independently

pg 1193

22
Q

need for NADPH only

A
  • oxidative: NADPH
  • nonoxidative: convert ribulose 5-P to glucose 6-P to produce more NADPH

pg 1193

23
Q

need for NADPH + ribose 5-P

A
  • oxidative: NADPH and ribulose 5-P
  • isomerase converts ribulose 5-P to ribose 5-P

pg 1193

24
Q

need for ribose 5-P only

A
  • only nonoxidative reactions
  • high NADPH inhibits G6PD
  • transketolase and transaldolase convert fructose 6-P and glyceraldehyde 3-P to ribose 5-P

pg 1193

25
Q

need for NADPH and pyruvate

A
  • oxidative: NADPH and ribulose 5-P
  • nonoxidative: convert ribulose 5-P to fructose 6-P and glyceraldehyde 3-P, glycolysis converts intermediates to pyruvate

pg 1193

26
Q

NADPH biological roles

A
  • electron donor for synthesis of: FAs, cholesterol, steroids
  • elecron donor for neutralization of ROS: hydrogen peroxide, superoxide, hydroxyl radical
  • reducing equivalents for cyt P450 monooxygenase system: biosynthesis of steroids, detoxification of xenobiotics and drugs
  • play role in phagocytosis -> destruction of pathogens by macrophages and neutrophils
  • substrate for synthesis of NO

pg 1195

27
Q

NADPH role in RBC

A

44:20 from lecture
* pentose phosphate pathway is the only source of NADPH in RBC

pg 1196

28
Q

G6PD deficiency

A
  • glucose 6-phosphate dehydrogenase
  • episodic hemolytic anemia induced by oxidative stress
  • RBC contain Heinz bodies (precipitated hemoglobin)
  • one of most common single gene disorders
  • X-linked (males predominantly affected)

pg 1197

29
Q

G6PD variants

A
  • Class I: very severe (< 10% of residual enzyme activity)
  • Class II: severe (acute hemolytic anemia)
  • Class III: moderate (10%-60% residual enzyme activity)
  • Class IV: no clinical symptoms (>60% residual enzyme activity)

pg 1198

30
Q

G6PD genetics

A
  • high degree of population specific polymorphism
  • > 400 putatively distinct G6PD variants identified
  • > 200 mutations -> most point missense
  • mutations result in altered enzyme kinetics -> E stability (majority of mutations), E active site, E allosteric sites

pg 1198

31
Q

G6PD precipitating factors

A
  • infections
  • foods containing fava beans substances: divicine and isouramil, suspected to bind and decrease GSH levels in RBC
  • certain drugs (ex: sulfonamides, nitrofurans, aspirin, etc)

pg 1199

Scientific Foundations (46 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions