475. Within the RBC, hypoxia stimulates glycolysis by which of the following regulatory pathwayse

a.      Hypoxia stimulates pyruvate dehydrogenase by increased 2,3-DPG

b.      Hypoxia inhibits hexokinase

c.      Hypoxia stimulates release of all glycolytic enzymes from Band -3 on RBC membrane

d.      Activation of the regulatory enzymes by high PH

 

Option C (Hypoxia stimulates release of all Glycolytic enzymes from Band 3 on RBC membranes)

Journal based question: References on which answer is based are provided at the end of explanation

Hypoxia causes Deoxygenation of Hemaglobin and Increases band 3 Tyrosine Phosphorylation. This stimulates the releasing of all Glycolytic enzymes from band 3 on the RBC membrane thereby stimulating Glycolysis

Glycolytic Enzymes and Band 3 on RBC membrane:

·        Band 3 is a multifunctional RBC membrane protein that plays several important roles in RBC metabolism and morphology

·        Band 3 membrane abundance and its organization within the RBC is important for normal anion exchange activity, cytoskeletal structure, cell shape and glycolytic activity

·        Glycolytic enzymes are organized into a complex on the human RBC membrane (Band 3)

·        The assembly and disassembly of the glycolytic enzymes from the band 3 complex is regulated by physiologically relevant stimuli.

·        Phosphorylation of band 3 or Deoxygenation of Hb can lead to release of all Glycolytic enzymes from the membrane, even though only a single site on band 3 is modified.

Thus Red cell deoxygenation and Band 3 tyrosine phosphorylation have been reported to accelerate glycolysis

·        Hypoxia causes deoxygenation of Hemaglobin and increases band 3 tyrosine phosphorylation and thereby stimulates glycolysis by releasing Glycolytic enzymes from Band 3 on the RBC membrane

“Based mainly on in vitro studies, it is believed that band-3 function is regulated by its phosphorylation status. Increased band-3 tyrosine phosphorylation has been shown to stimulate glycolysis. Studies have indicated that hypoxia increases band-3 tyrosine phosphorylation in vitro” – Journal

Reference: Journal articles

“Assembly and regulation of a glycolytic enzyme complex on the human erythrocytic membrane” (http://www.pass.org/cgi/abstract/full/102/7/2402)