Page 88 - 69_01

A. GARRIDO, J.M BAUTISTA ANAL. REAL ACAD. NAL. FARM.

un desajuste en el balance de las cargas eléctricas o por impedimento estérico, corresponden
valores disminuidos de la actividad de la enzima en aquellos pacientes portadores de dichas
mutaciones.

Palabras Clave: Enzimopatía eritrocitos.? Anemias hemolíticas.? Mutaciones PK

SUMMARY

Pyruvate kinase deficiencies and hemolytic anemias

The enzyme pyruvate kinase (PK) catalyses the transformation of phosphoenolpy-
ruvate and ADP to pyruvate and ATP. The activity of this ubiquitous enzyme is essential for
the central carbohydrate metabolism. Deficiency in PK activity causes non-espherocitic
haemolytic anaemia, due to alterations in the metabolism of erythrocytes. The red cell lacks
alternate metabolic pathways for pyruvate, and can not cope with the enzymatic fault by
increasing the synthesis of the protein. Clinical symptoms in patients harbouring a PK
deficiency with anaemia, which may lead to death.

Several difficulties appear in the biochemistry caracterization of the enzyme, which
led to the application of molecular biology tools. The present work was performed on 10 PK
deficient patients. By means of molecular analysis, we have found 11 different mutations in
the 17 alleles analysed, three of which, G694A, A1150G y G1154A, have not been
previously reported.

Changes in the protein structure caused by mutations which introduce steric hin-
drance or substitutions in charged residues, analised by molecular modeling, showed a clear
correlation with the reduction in PK activity in the patients studied.

Key words: Erythrocyte enzymopathies.? Haemolytic anemias.? Mutations PK

Introducción

Los hematíes, eritrocitos o glóbulos rojos son células sanguíneas, que
además de transportar el oxígeno desde los pulmones a los tejidos, realizan
también otras funciones importantes y por ello contienen varios catabolitos y
enzimas. Aunque los eritrocitos maduros no tienen núcleo, mitocondrias, ni
retículo endoplásmico y por ello no puede sintetizar proteínas, glucógeno,
lípidos, ni llevar a cabo la fosforilación oxidativa son capaces de metabolizar
la glucosa y otros monosacáridos. En consecuencia, su metabolismo, muy
reducido, queda limitado a la glucolisis, ruta de las pentosas fosfato, ciclo del

104