A Thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, for the Degree of Doctor of Philosophy. / A deficiency of the enzyme NADP dependent xylitol dehydrogenase
(L-xylulose reductase) has previously been found to be the cause
of chronic essential pentosuria. Essential pentosuria is a
recessively inherited condition which is marked by the continual
excretion of relatively large amounts of the enzymes substrate,
L-xylulose. The major objective of the study described was to find
a simple method for the identification of individuals who are
heterozygous for the "pentosuria" and normal alleles. The pentosuria
allele could then be used as a gene marker in linkage studies aimed
at mapping the L-xylulose reductase locus. A L-xylulose reductase
assay suitable for the identification of carriers of essential
pentosuria was developed and tested on members of a South African
Lebanese family in which the inheritance of pentosuria had
previously been suggested to be dominant. It was found that family
members could, on the basis of their L-xylulose reductase activities,
be classified as either normal, heterozygous or homozygous for the
pentosuria allele. Measurements of serum L-xylulose concentrations
revealed that pentosuria is, contrary to the previous report, .
recessively inherited in this family.
A sample of the local Ashkenazi Jewish population was screened
for pentosuria carriers. Six out of the 237 individuals screened
were found (on the basis of their L-xylulose reductase activities
and from the results of a loading test), to carry the pentosuria
allele. The frequency of the pentosuria allele in this population
was estimated from the apparent heterozygote frequency to be 0.0127.
Linkage analyses were carried out on the families of the identified
heterozygotes and on members of the Lebanese family mentioned above.
No evidence of tight linkage was found between the pentosuria
allele's locus and those coding for various red cell antigens,
red cell enzymes and serum proteins.
Kinetic, chromatographic and electrophoretic studies
revealed that the red cells of normal individuals contain two
distinct L-xylulose reductases, a minor and a major isozyme.
Pentosurics lack the major isozyme but appear to have approximately
normal amounts of the minor isozyme. The minor isozyme is
e1ectrophoretica 1 1 y distinct from the major isozyme, has markedly
higher Michael is constants for the substrates L-xylulose and
xylitol and shows a lower pH optimum when catalysing the oxidation
of xylitol. Electrophoresis also revealed that liver tissue
contains two L-xylulose reductases which occur in similar proportions
to those of red cells but which migrate at slightly different rates. / WHSLYP2016
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/21256 |
| Date | January 1984 |
| Creators | Lane, Anthony Bruce |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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