Editing Pyruvate kinase deficiency (section)

==Pathophysiology==
[[File:ATP-xtal-3D-balls.png|thumb|ATP-3D]]
Pyruvate kinase is the last enzyme involved in the [[Glycolysis|glycolytic process]], transferring the phosphate group from phosphenol pyruvate to a waiting [[adenosine diphosphate]] (ADP) molecule, resulting in both [[adenosine triphosphate]] (ATP) and [[Pyruvic acid|pyruvate]]. This is the second ATP producing step of the process and the third regulatory reaction.<ref name=":7" /><ref name="patient" /> Pyruvate kinase deficiency in the red blood cells results in an inadequate amount of or complete lack of the enzyme, blocking the completion of the [[Glycolysis|glycolytic pathway]]. Therefore, all products past the block would be deficient in the red blood cell. These products include ATP and pyruvate.<ref name=":3" />

Mature [[Red blood cell|erythrocytes]] lack a [[Cell nucleus|nucleus]] and [[Mitochondrion|mitochondria]]. Without a nucleus, they lack the ability to synthesize new proteins so if anything happens to their pyruvate kinase, they are unable to generate replacement enzymes throughout the rest of their life cycle. Without mitochondria, erythrocytes are heavily dependent on the anaerobic generation of ATP during glycolysis for nearly all of their energy requirements.<ref name=":8" />

With insufficient ATP in an erythrocyte, all active processes in the cell come to a halt. Sodium potassium [[ATPase]] pumps are the first to stop. Since the [[cell membrane]] is more permeable to [[potassium]] than [[sodium]], potassium leaks out. Intracellular fluid becomes [[Tonicity|hypotonic]], water moves down its concentration gradient out of the cell. The cell shrinks and cellular death occurs, this is called 'dehydration at cellular level'.<ref name=":3"/><ref>{{Cite book|url=https://books.google.com/books?id=UCDcZFUo0YIC|title=Haematology Made Easy|date=2013-02-06|publisher=AuthorHouse|isbn=9781477246511|page=181|language=en}}</ref> This is how a deficiency in pyruvate kinase results in hemolytic anaemia, the body is deficient in red blood cells as they are destroyed by lack of ATP at a larger rate than they are being created.<ref>{{Cite journal|last1=Jacobasch|first1=Gisela|last2=Rapoport|first2=Samuel M.|date=1996-04-01|title=Chapter 3 Hemolytic anemias due to erythrocyte enzyme deficiencies|journal=Molecular Aspects of Medicine|volume=17|issue=2|pages=143–170|doi=10.1016/0098-2997(96)88345-2|pmid=8813716}}</ref>