Diversity in Residual Alanine Glyoxylate Aminotransferase Activity in Hyperoxaluria Type I: Correlation with Pyridoxine Responsiveness

In this paper we studied the glyoxylate-dependent transamination of L-alanine and L-glutamate in human liver homogenates in order to develop a reliable method for the determination of true alanine:glyoxylate aminotransferase activity in liver homogenates from patients suspected to suffer from hyperoxaluria type I. Measurements were made according to two protocols described in literature in control human liver homogenates which were either untreated or treated with an antiserum raised against purified alanine:glyoxylate aminotransferase. The results obtained show that enzyme activity can best be determined at pH 8.0 as compared to pH 7.4 since the former leads to a higher sensitivity of the method. Alanine:glyoxylate aminotransferase activities measured at pH 8.0 are approximately 50% higher compared to the enzyme activities measured at pH 7.4. Accordingly, it is proposed to measure alanine:glyoxylate aminotransferase activity at pH 8.0 using the newly determined correction factor as described in this paper.

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Human liver l-alanine — glyoxylate aminotransferase: Characteristics and activity in controls and hyperoxaluria type I patients using a simple spectrophotometric method

Clinica Chimica Acta ◽

10.1016/0009-8981(90)90084-6 ◽

1990 ◽

Vol 189 (2) ◽

pp. 139-144 ◽

Cited By ~ 18

Author(s):

R.J.A. Wanders ◽

J. Ruiter ◽

C.W.T. van Roermund ◽

R.B.H. Schutgens ◽

R. Ofman ◽

...

Keyword(s):

Spectrophotometric Method ◽

Human Liver ◽

Type I ◽

Hyperoxaluria Type I ◽

Glyoxylate Aminotransferase ◽

Hyperoxaluria Type

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Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

BioMed Research International ◽

10.1155/2013/687658 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 21

Author(s):

Angel L. Pey ◽

Armando Albert ◽

Eduardo Salido

Keyword(s):

Primary Hyperoxaluria ◽

Therapeutic Strategies ◽

Single Amino Acid ◽

Type I ◽

Protein Homeostasis ◽

Primary Hyperoxaluria Type ◽

Hyperoxaluria Type I ◽

Glyoxylate Aminotransferase ◽

Primary Hyperoxaluria Type I ◽

Hyperoxaluria Type

Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP) as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.

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