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The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: a possible cause for poor long-term prognosis in classic galactosemia.
Med Hypotheses. 2005; 65(6):1051-7.MH

Abstract

Classic galactosemia is an autosomal recessive disorder that is caused by activity deficiency of the UDP-galactose uridyl transferase (GALT). The clinical spectrum of classic galactosemia differs according to the type and number of mutations in the GALT gene. Short-term clinical symptoms such as jaundice, hepatomegaly, splenomegaly and E. coli sepsis are typically associated with classic galactosemia. These symptoms are often severe but quickly ameliorate with dietary restriction of galactose. However, long-term symptoms such as mental retardation and primary ovarian failure do not resolve irrespective of dietary intervention or the period of initial dietary intervention. There seem to be an association between deficient galactosylation of cerebrosides and classic galactosemia. Galactocerebrosides and glucocerebrosides are the primary products of the enzyme UDP-galactose:cerebroside galactosyl transferase (CGT). There has been an observation of deficient galactosylation coupled with over glucosylation in the brain tissue specimens sampled from deceased classic galactosemia patients. The plausible mechanism with which the association between GALT and CGT had not been explained before. Yet, UDP-galactose serves as the product of GALT as well as a substrate for CGT. In classic galactosemia, there is a consistent deficiency in cerebroside galactosylation. We postulate that the molecular link between defective GALT enzyme, which result in classic galactosemia; and the cerebroside galactosyl transferase, which is responsible for galactosylation of cerebrosides is dependent on the cellular concentrations of UDP-galactose. We further hypothesize that a threshold concentration of UDP-galactose exist below which the integrity of cerebroside galactosylation suffers.

Authors+Show Affiliations

Biotechnology Section, Department of Health Sciences, Vaal University of Technology, Block F110, Andries Potgieter Boulevard, Vanderbijlpark 1900, South Africa. justice@vut.ac.zaNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16125333

Citation

Lebea, Phiyani Justice, and Pieter J. Pretorius. "The Molecular Relationship Between Deficient UDP-galactose Uridyl Transferase (GALT) and Ceramide Galactosyltransferase (CGT) Enzyme Function: a Possible Cause for Poor Long-term Prognosis in Classic Galactosemia." Medical Hypotheses, vol. 65, no. 6, 2005, pp. 1051-7.
Lebea PJ, Pretorius PJ. The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: a possible cause for poor long-term prognosis in classic galactosemia. Med Hypotheses. 2005;65(6):1051-7.
Lebea, P. J., & Pretorius, P. J. (2005). The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: a possible cause for poor long-term prognosis in classic galactosemia. Medical Hypotheses, 65(6), 1051-7.
Lebea PJ, Pretorius PJ. The Molecular Relationship Between Deficient UDP-galactose Uridyl Transferase (GALT) and Ceramide Galactosyltransferase (CGT) Enzyme Function: a Possible Cause for Poor Long-term Prognosis in Classic Galactosemia. Med Hypotheses. 2005;65(6):1051-7. PubMed PMID: 16125333.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The molecular relationship between deficient UDP-galactose uridyl transferase (GALT) and ceramide galactosyltransferase (CGT) enzyme function: a possible cause for poor long-term prognosis in classic galactosemia. AU - Lebea,Phiyani Justice, AU - Pretorius,Pieter J, Y1 - 2005/08/25/ PY - 2005/05/24/received PY - 2005/06/09/revised PY - 2005/06/10/accepted PY - 2005/8/30/pubmed PY - 2006/1/6/medline PY - 2005/8/30/entrez SP - 1051 EP - 7 JF - Medical hypotheses JO - Med Hypotheses VL - 65 IS - 6 N2 - Classic galactosemia is an autosomal recessive disorder that is caused by activity deficiency of the UDP-galactose uridyl transferase (GALT). The clinical spectrum of classic galactosemia differs according to the type and number of mutations in the GALT gene. Short-term clinical symptoms such as jaundice, hepatomegaly, splenomegaly and E. coli sepsis are typically associated with classic galactosemia. These symptoms are often severe but quickly ameliorate with dietary restriction of galactose. However, long-term symptoms such as mental retardation and primary ovarian failure do not resolve irrespective of dietary intervention or the period of initial dietary intervention. There seem to be an association between deficient galactosylation of cerebrosides and classic galactosemia. Galactocerebrosides and glucocerebrosides are the primary products of the enzyme UDP-galactose:cerebroside galactosyl transferase (CGT). There has been an observation of deficient galactosylation coupled with over glucosylation in the brain tissue specimens sampled from deceased classic galactosemia patients. The plausible mechanism with which the association between GALT and CGT had not been explained before. Yet, UDP-galactose serves as the product of GALT as well as a substrate for CGT. In classic galactosemia, there is a consistent deficiency in cerebroside galactosylation. We postulate that the molecular link between defective GALT enzyme, which result in classic galactosemia; and the cerebroside galactosyl transferase, which is responsible for galactosylation of cerebrosides is dependent on the cellular concentrations of UDP-galactose. We further hypothesize that a threshold concentration of UDP-galactose exist below which the integrity of cerebroside galactosylation suffers. SN - 0306-9877 UR - https://www.unboundmedicine.com/medline/citation/16125333/The_molecular_relationship_between_deficient_UDP_galactose_uridyl_transferase__GALT__and_ceramide_galactosyltransferase__CGT__enzyme_function:_a_possible_cause_for_poor_long_term_prognosis_in_classic_galactosemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(05)00353-1 DB - PRIME DP - Unbound Medicine ER -