Red cell glycolytic enzyme disorders caused by mutations: an update

Area of Science:

• Biochemistry
• Genetics
• Cell Biology

Background:

• Glycolysis is a fundamental ATP generation pathway present in all cell types.
• Erythrocytes rely exclusively on glycolysis for ATP synthesis due to their lack of mitochondria.
• Deficiencies in erythrocyte glycolytic enzymes are linked to various clinical manifestations.

Purpose of the Study:

• To review erythrocyte glycolytic pathway deficiencies.
• To highlight the frequency and causes of these deficiencies, focusing on genetic mutations.
• To emphasize the role of enzyme structure and function in disease pathogenesis.

Main Methods:

• Review of known erythrocyte glycolytic enzyme deficiencies.
• Analysis of reported cases and their underlying causes, particularly genetic mutations.
• Discussion of molecular modeling studies based on enzyme crystal structures.

Main Results:

• Erythrocyte glycolysis deficiencies affect all enzymes in the pathway, with varying frequencies.
• Pyruvate kinase deficiency is the most common, with approximately 500 known cases, ~200 due to mutations.
• Other rare mutations, such as phosphoglycerate mutase BB type, are documented, with only one case reported.
• Mutations occur in coding sequences and include missense, deletions, insertions, splice defects, premature stop codons, and promoter mutations.

Conclusions:

• Genetic mutations are a significant cause of erythrocyte glycolytic enzyme deficiencies.
• Understanding enzyme structure through molecular modeling aids in elucidating the impact of mutations on enzyme function.
• Further research into enzyme structure-function relationships is crucial for understanding and potentially treating these conditions.