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    Anaerobic Metabolism of Carbohydrates in RBC - Lectue XXI

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    Saul
    G6PD deficiency is the most common enzymopathy worldwide, affecting 400 million people. It leads to hemolytic anemia in some due to inadequate production of protective thiols during oxidative stress. Erythrocytes are particularly vulnerable because they lack mitochondria and other NADPH-producing enzymes, making them reliant on G6PD to regenerate NADPH and combat oxidative stress.

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    Anaerobic Metabolism of Carbohydrates in RBC - Lectue XXI

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    Saul
    56 views4 pages
    G6PD deficiency is the most common enzymopathy worldwide, affecting 400 million people. It leads to hemolytic anemia in some due to inadequate production of protective thiols during oxidative stress. Erythrocytes are particularly vulnerable because they lack mitochondria and other NADPH-producing enzymes, making them reliant on G6PD to regenerate NADPH and combat oxidative stress.

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    G6PD deficiency is the most common enzymopathy worldwide, affecting 400 million people. It leads to hemolytic anemia in some due to inadequate production of protective thiols during oxidative stress. Erythrocytes are particularly vulnerable because they lack mitochondria and other NADPH-producing enzymes, making them reliant on G6PD to regenerate NADPH and combat oxidative stress.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    56 views4 pages

    Anaerobic Metabolism of Carbohydrates in RBC - Lectue XXI

    Uploaded by

    Saul
    G6PD deficiency is the most common enzymopathy worldwide, affecting 400 million people. It leads to hemolytic anemia in some due to inadequate production of protective thiols during oxidative stress. Erythrocytes are particularly vulnerable because they lack mitochondria and other NADPH-producing enzymes, making them reliant on G6PD to regenerate NADPH and combat oxidative stress.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 4

    TBL : Glucose 6-phosphate dehydrogenase (G6PD)

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most


    common enzymopathy worldwide, affecting an estimated 400 million
    people. The major morbidity associated with G6PD deficiency is
    hemolytic anemia, which in some individuals may be life-
    threatening. G6PD deficiency leads to inadequate production of
    protective intracellular thiols during oxidative stress. While the
    deficiency is ubiquitous across cell types, erythrocytes are reduced
    oxidized
    particularly vulnerable to oxidative stress in the G6PD-deficient glutathione
    glutathione
    state. Bubp, et al., Pharmacy & Therapeutics, 40(9): 572–574

    Question 1. How does G6PD deficiency lead to hemolytic anemia?


    Lack of G6PD would lead to decreased glucose 6-phosphate in the pentose phosphate
    pathway, which would ultimately lead to decreased NADPH. Production of NADPH by
    G6PD is essential in erythrocytes, which are susceptible to damage by reactive oxygen
    species because they lack other NADPH-producing enzymes.

    Question 2. Why are erythrocytes more vulnerable to oxidative stress


    in the G6PD-deficient state?
    In erythrocytes, there are no mitochondria leading to anaerobic conditions. This, in turn,
    prevents NADH from being re-oxidized by O2, which forces NAD+ to be generated by
    reduction of pyruvate to lactate (fermentation).
    TBL : synthesis of of 2,3-bis phosphoglycerate (2,3-BPG)
    2,3-BPG is an important by-product of glycolysis in the
    RBC. It is synthesized through the conversion of 1,3-
    BPG to 2,3-BPG catalyzed by 2,3-BPG mutase which
    also has a phosphatase activity. Therefore the enzyme
    controls both synthesis and hydrolysis of 2,3-BPG.

    Question 1. Which reaction of glycolysis is bypassed


    during the synthesis of 2,3-BPG?
    Bypasses the conversion of 1,3-BPG to 3-PPG

    Question 2. How does synthesis of 2,3-BPG affect the


    energy yield of glycolysis?
    Synthesis of 2,3-BPG reduces production of energy in glycolysis

    Question 3. what is the role of 2,3-BPG in


    erythrocytes?
    2,3-BPG is used to produce 3-PPG through 2,3-BPG phosphatase. 3-PPG then is used to form pyruvate after several steps, which can then form lactate and
    generate NADH. Conversion of hemoglobin from R state to T state and can release oxygen more easily. Higher level of oxygen produces more 2,3-BPG
    which can reduce affinity of hemoglobin for oxygen, which can release oxygen more easily and travel to tissues.
    TBL : Regulation of glycolysis

    The flux of glucose through the glycolytic pathway is regulated to maintain nearly constant ATP levels.
    Therefore, glycolysis is under tight regulation.

    Question 1. Discuss the effects of the following factors on the rate of glycolysis:
    • ATP consumption
    • NADH regeneration
    ATP Consumption = Leads to increased rate of glycolysis due to accommodate decreased concentration of ATP
    present

    NADH Regeneration = Leads to decreased rate of glycolysis since pathway does not need to work hard to produce
    more NADH
    Question 2. Predict the effects of allosteric regulation of the following enzymes by ATP on the rate of glycolysis:
    • Hexokinase
    • PFK-1
    • Pyruvate kinase
    Hexokinase = Allosterically bind to enzymes and lower rate of glycolysis (if ATP levels are high, decreased glycolysis)

    PFK-1 = Allosterically bind to enzymes and lower rate of glycolysis

    Pyruvate kinase = Allosterically bind to enzymes and lower rate of glycolysis


    TBL : Rate of glycolysis and pentose phosphate pathways in tumors

    Cancer cells undergo a metabolic switch from oxidative phosphorylation to glycolysis. The majority of
    cancer cells depend on high rates of glycolysis for growth and survival, even when there is sufficient
    oxygen. This type of aerobic glycolysis is called the Warburg effect. Yu, et al., Journal of cancer, 2017; 8(17): 3430- 3440

    Question. Discuss the possible explanations for tumor cells use of the glycolysis pathway.

    • Faster way of producing ATP


    ◦Are in a rush and want to divide more, need more ATP, user glycolysis for that
    • Dividing quickly
    ◦Need some molecules produced from glycolysis for their metabolic pathways to produce molecules needed for
    tumor cells
    • Need NADPH
    ◦NADPH protects cells against oxidative damage which cancer cells need too, especially against anti-cancer
    drugs. It is a form of adaption against drugs that cause oxidative damage. Both glycolysis and pentose
    phosphate pathways increase in tumor cells due to increased NADPH.

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