Pentosuria Research Articles

Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

Dicarbonyl/L-xylulose reductase (DCXR; SDR20C1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily catalyzes the reduction of α-dicarbonyl compounds and monosaccharides. Its role in the metabolism of L-xylulose has been known since 1970, when essential pentosuria was found to be associated with DCXR deficiency. Despite its early discovery, our knowledge about the role of human DCXR in normal physiology and pathophysiology is still incomplete. Sporadic studies have demonstrated aberrant expression in several cancers, but their physiological significance is unknown. In reproductive medicine, where DCXR is commonly referred to as 'sperm surface protein P34H', it serves as marker for epididymal sperm maturation and is essential for gamete interaction and successful fertilization. DCXR exhibits a multifunctional nature, both acting as a carbonyl reductase and also performing non-catalytic functions, possibly resulting from interactions with other proteins. Recent observations associate DCXR with a role in cell adhesion, pointing to a novel function involving tumour progression and possibly metastasis. This review summarizes the current knowledge about human DCXR and its orthologs from mouse and Caenorhabditis elegans (DHS-21) with an emphasis on its multifunctional characteristics. Due to its close structural relationship with DCXR, carbonyl reductase 2 (Cbr2), a tetrameric enzyme found in several non-primate species is also discussed. Similar to human DCXR, Cbr2 from golden hamster (P26h) and cow (P25b) is essential for sperm-zona pellucida interaction and fertilization. Because of the apparent similarity of these two proteins and the inconsistent use of alternative names previously, we provide an overview of the systematic classification of DCXR and Cbr2 and a phylogenetic analysis to illustrate their ancestry.

Human L-xylulose reductase variation: family and population studies.

Only one of the two main L-xylulose reductases present in human tissue is deficient in individuals with essential pentosuria (Lane, 1985). The isozyme which is affected by the pentosuria mutation occurs as mitochondrial and cytosolic forms in normal individuals, whereas the other isozyme (which is not affected by the mutation) occurs only in the cytosol. A new assay of red cell L-xylulose reductase activity has facilitated the identification of carriers of the essential pentosuria allele at both family and population levels. Reinvestigation of a Lebanese family in which pentosuria has previously been thought to be dominantly inherited reveals that the condition is recessively inherited in this family as well. A minimum estimate of the frequency of the pentosuria allele in an Ashkenazi-Jewish population, calculated from the apparent heterozygote frequency, is 0.0127. The likelihood of the Ashkenazi and Lebanese pentosuria alleles being the same is discussed.

On the nature of L-xylulose reductase deficiency in essential pentosuria.

Essential pentosuria is the result of a partial deficiency of L-xylulose reductase. Red blood cells of normal individuals have been found to contain two L-xylulose reductases: a major and a minor isozyme. Red cells from pentosurics contain only one isozyme. The residual enzyme of pentosurics and the normal minor isozyme have similar Michaelis constants for L-xylulose and xylitol, similar activity responses to pH, and similar rates of migration when electrophoresed or subjected to ion-exchange chromatography. It is suggested that homozygosity for the pentosuria allele results in the absence of the major isozyme and that the residual isozyme of pentosurics is identical to the minor isozyme of normal individuals.

The enzymatic defect in essential pentosuria.

Abstract The enzyme defect in pentosuria has been assumed to be NADP-linked xylitol dehydrogenase, a specific enzyme found in mammalian livers. In the red blood cells of three homozygous pentosuric subjects, the activity of NADP-linked xylitol dehydrogenase was found to be subnormal. The enzyme has a Michaelis-constant value for NADP that is 10 to 20 times higher than that found in normal persons. In a heterozygous subject, two activities, one normal, one abnormal, appeared to exist. This study confirms by direct biochemical means the site of the metabolic defect in pentosuria.

Pentosuria in a North American Indian.

PENTOSURIA, one of Garrod's original four inborn errors of metabolism1, is usually believed to occur almost entirely among people of Jewish descent, whose antecedents can be traced to eastern Europe2. The only well authenticated cases of this disorder to be reported among individuals of other ethnic origin have been in four Lebanese families3,4. We wish to report a case of essential pentosuria in a North American Indian.

Carbohydrate metabolism in pentosuria.

Article1 August 1960CARBOHYDRATE METABOLISM IN PENTOSURIAHOWARD H. HIATT, M.D.HOWARD H. HIATT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-53-2-372 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPentosuria, or chronic essential pentosuria, is one of four hereditary disturbances which Garrod1over 50 years ago classified as inborn errors of metabolism. It is an innocuous condition, presumably present from birth, and has been described almost exclusively in Jews. The characteristic urinary excretion of a relatively constant amount ofL-xylulose, varying from 1 to 4 gm. per 24 hours,2unrelated to dietary factors, distinguishes hereditary pentosuria from several other situations in which milligram quantities of certain 5-carbon sugars other thanL-xylulose are found in the urine. These include alimentary pentosuria, in which arabinose or xylose may be excreted following...Bibliography1. Garrod AE: Inborn errors of metabolism, Lancet 2: 217, 1908. Google Scholar2. EnklewitzLasker MM: The origin of L-xyloketose (urine pentose), J. Biol. Chem. 110: 443, 1935. CrossrefGoogle Scholar3. TowerPetersPogorelskin DBELMA: Nature and significance of pentosuria in neuromuscular disease, Neurology 6: 37, 125, 1956. CrossrefMedlineGoogle Scholar4. FuttermanRoe SJH: The identification of ribulose and L-xylulose in human and rat urine, J. Biol. Chem. 215: 257, 1955. CrossrefMedlineGoogle Scholar5. HoreckerHiatt BLHH: Pathways of carbohydrate metabolism in normal and neoplastic cells, New England J. Med. 258: 177, 225, 1958. CrossrefMedlineGoogle Scholar6. HoreckerMehler BLAH: Carbohydrate metabolism, Ann. Rev. Biochem. 24: 207, 1955. CrossrefMedlineGoogle Scholar7. Margolis JI: Chronic pentosuria and migraine, Am. J. M. Sc. 177: 348, 1929. CrossrefGoogle Scholar8. TousterHutchesonRice ORML: The influence of D-glucuronolactone on the excretion of L-xylulose by humans and guinea pigs, J. Biol. Chem. 215: 677, 1955. CrossrefMedlineGoogle Scholar9. TousterMayberryMcCormick ORHDB: The conversion of 1-13C-D-glucuronolactone to 5-13 C-L-xylulose in a pentosuric human, Biochim. et Biophys. Acta 25: 196, 1957. CrossrefMedlineGoogle Scholar10. TousterReynoldsHutcheson OVHRM: The reduction of L-xylulose to xylitol by guinea pig liver mitochondria, J. Biol. Chem. 221: 697, 1956. CrossrefMedlineGoogle Scholar11. HollmanTouster SO: The L-xylulose-xylitol enzyme and other polyol dehydrogenases of guinea pig liver mitochondria, J. Biol. Chem. 225: 87, 1957. CrossrefMedlineGoogle Scholar12. Hiatt HH: Pentosuria, in The biochemistry of molecular diseases, McGraw-Hill, New York, in press. Google Scholar13. Hiatt HH: Studies of ribose metabolism. IV. The metabolism of D-glucuronolactone in normal and pentosuric subjects, Biochim. et Biophys. Acta 28: 645, 1958. CrossrefMedlineGoogle Scholar14. TaborHayaishi HO: The excretion of imidazoleacetic acid riboside following the administration of imidazoleacetic acid or histamine to rats, J. Am. Chem. Soc. 77: 505, 1955. CrossrefGoogle Scholar15. Hiatt HH: Studies of ribose metabolism. VI. Pathways of ribose synthesis in man, J. Clin. Investigation 37: 1461, 1958. CrossrefMedlineGoogle Scholar16. FreedbergFeingoldHiatt IMDSHH: Serum and urine L-xylulose in pentosuric and normal subjects and in individuals with pentosuria trait, Biochem. and Biophys. Research Communications 1: 328, 1959. CrossrefGoogle Scholar17. HickmanAshwell JG: A sensitive and stereo-specific enzymatic assay for xylulose, J. Biol. Chem. 234: 758, 1959. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication April 4, 1960.Presented in part at the Forty-first Annual Session of The American College of Physicians, San Francisco, California, April 4, 1960.From the Department of Medicine, Harvard Medical School, and the Department of Medical Research, Beth Israel Hospital, Boston, Massachusetts.This work was supported by grants from the U. S. Public Health Service, the American Cancer Society, and the Jane Coffin Childs Memorial Fund for Medical Research.Requests for reprints should be addressed to Howard H. Hiatt, M.D., Beth Israel Hospital, 330 Brookline Avenue, Boston 15, Massachusetts. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe complex human urinary sugar profile: determinants revealed in the cross-sectional KarMeN studyDehydrogenases: Glucose-6-Phosphate Dehydrogenase, 6-Phosphogluconate Dehydrogenase, Glutathione Reductase, Methemoglobin Reductase, Polyol DehydrogenasesIncidence of Pentosuria 1 August 1960Volume 53, Issue 2Page: 372-379KeywordsCarbohydrate metabolismExcretionHealth services researchHospital medicineInborn errors of metabolismJewish peopleMedical servicesResearch fundingUrineXylose Issue Published: 1 August 1960 PDF downloadLoading ...

The inheritance of essential pentosuria.

The inheritance of essential pentosuria.

Essential pentosuria: renal or enzymic disorder.

ESSENTIAL pentosuria is a rare, recessive genetic metabolic disorder characterized by the excretion of gram quantities of L-xylulose. It was included among Garrod's “inborn errors of metabolism”1 and has usually been considered to be the result of an enzyme deficiency. Garrod's original concept of a hereditary metabolic anomaly has been broadened by some to include renal defects, and, in regard to essential pentosuria, Knox2 has recently stated, “the paramount question of a renal or an enzymic mechanism is still to be decided”.

Pentose metabolism and pentosuria

The metabolism of pentoses is reviewed. The pentose phosphate pathway (6-phosphogluconate oxidation pathway) is the source of tissue d-ribose and perhaps d-2-deoxyribose as well. In certain tissues it also contributes to the net oxidation of glucose and probably supplies reduced triphosphopyridine nucleotide for biosynthetic reactions. Little is known about the importance of the glucuronate-xylulose cycle, except that from it the l-ascorbic acid produced by the rat is derived. It is significant that l-xylulose, the characteristic urinary sugar of essential pentosuria, is an intermediate in this pathway. It can be stated with considerable certainty that essential pentosuria is a harmless biochemical anomaly linked to a rare recessive gene which is virtually restricted to individuals of Jewish origin. The exact nature of the defect has not been clearly determined. The questionable existence of other types of pentosuria is discussed.

THE CONVERSION IN VIVO OF XYLITOL TO GLYCOGEN VIA THE PENTOSE PHOSPHATE PATHWAY

Studies in this laboratory designed to elucidate the metabolism of L-xylulose, the characteristic urinary sugar of essential pentosuria, have shown that n-glucuronolactone is a precursor of the ketopentose in guinea pigs and in humans (1, 2) and that there are enzymes in guinea pig liver which can interconvert L-xylulose and xylitol as well as xylitol and D-xylulose (3, 4). The discovery that n-xylulose 5-phosphate is an intermediate in the pentose phosphate shunt (6-phosphogluconate oxidation pathway) (5, 6) suggested that glucuronate and the xyluloses might be ultimately metabolized via this pathway (4, 7). A kinase has indeed been found in calf liver which can convert n-xylulose to n-xylulose 5-phosphate (8). These findings suggest that the following sequence of reactions occurs in mammals: n-glucuronate --) L-xylulose G= xylitol ti n-xylulose + D-xylulose 5-phosphate. Since the formulation of this sequence is based upon work done on different species and partly on enzymatic studies performed in vitro, it seemed desirable to obtain evidence in tivo regarding its physiological occurrence. The tracer experiments reported elsewhere (2) have demonstrated the conversion of n-glucuronolactone to L-xylulose in a pentosuric human through reactions involving loss of the carboxyl carbon of the former compound, with the aldehydic carbon becoming the fifth carbon of the pentose. The present paper reports a study of the metabolic fate of a compound which is intermediate in the reaction sequence shown above. Xylitol-l-Cl4 was chosen because it can be conveniently prepared from the readily available n-xylose-1-CY4. n-Ribose, known to be metabolized via the pentose phosphate shunt (9), and n-xylose were tested for comparative purposes. A recent report has shown that the latter is also metabolized via this pathway (10). It was first demonstrated that xylitol is oxidized in vivo to carbon dioxide. A study was then undertaken to determine whether the distribution of

The Diagnosis of the Less Common Meliturias: Including Pentosuria and Fructosuria

The Diagnosis of the Less Common Meliturias: Including Pentosuria and Fructosuria

PENTOSURIA ASSOCIATED WITH DIABETES MELLITUS

There has been no evidence to show that essential pentosuria is related in any way to diabetes mellitus, and no complete report of their combined occurrence can be found in the literature. 1 In the first case presented here the patient was suffering from both essential pentosuria and diabetes mellitus. By way of comparison a case of uncomplicated essential pentosuria is also reported. Essential pentosuria is a hereditary abnormality of metabolism characterized by continuous excretion of small amounts of pentose in the urine, unaffected by alterations in the diet. The first case of this disorder was reported by Salkowski and Jastrowitz 2 in 1892. Since then reports of more than 170 cases have appeared in the literature. The incidence of this disorder in the general population is estimated by Blatherwick 3 to be 1:50,000. The pentose excreted has been found in most instances to be levorotatory xylulose, formerly called l

PENTOSURIA AND DIABETES MELLITUS

Although recognized¹in 1892, few cases of chronic essential pentosuria have been reported. Enklewitz and Lasker²in 1933 were able to find reports of 100 cases, to which they added 12. They pointed out, however, that the condition is not excessively rare if consistently looked for in all instances in which a small amount of reducing substances' is found in the urine. Marble¹reported in 1932 that 3 cases had been found at the Joslin Clinic in a series of 9,000 cases of mellituria and by 1940 was able to report recognition of 9 cases. He emphasized the likelihood of their being mistakenly classified as examples of renal glycosuria unless the ty[ill] of urinary sugar is determined. Obviously there is equal danger of their being mistaken for cases of diabetes mellitus and of being treated as such. The occurrence of chronic pentosuria in association with diabetes mellitus

PENTOSURIA IN CHILDREN

Pentosuria is not a rare condition, although the opportunity to study cases in detail does not frequently present itself. We were particularly fortunate in having the opportunity to observe four cases in children within a year. No attempt will be made to review the literature, as Margolis 1 recently gave a complete bibliography of the subject and a review of seventy-eight cases. Among them were six in children under 15 years of age. There are three chief types: (1) alimentary pentosuria, (2) pentosuria associated with diabetes and (3) essential pentosuria. The alimentary type of pentosuria occasionally follows the ingestion of a large amount of fruit. Klercker 2 stated that pentosuria could be traced to the ingestion of nucleoprotein, but his impression is not universally accepted. The excretion of pentose by diabetic persons has often been described. We have examined the urine of diabetic children under our observation and frequently have

PENTOSURIA

A variety of reducing substances is demonstrable under varying conditions in the human urine. In view of the danger of hypoglycemic shock as a result of nonindicated doses of insulin, it becomes a matter of more than theoretical importance to determine the nature of the substance present in the urine of a patient suspected of having diabetes. It need hardly be emphasized that a reduction of copper solutions is not sufficient for a diagnosis of diabetes. Even a blood sugar higher than normal, as in the case to be presented, may lead one astray. A frequent source of error is the presence of fructose in the urine. Occasionally, as in the present case, one is dealing with pentosuria. While essential pentosuria is probably of more frequent occurrence than is generally recognized, the reported cases are not numerous, and the following case is that of the youngest patient on record. Pentose

REPORT OF A CASE OF ESSENTIAL PENTOSURIA IN BROTHER AND SISTER

It will be recalled that two types of pentosuria1exist: (1) the alimentary type, characterized by the presence of optically active xylose or arabinose in the urine, which follows the ingestion of large amounts of pentose-containing foods2such as apples, cherries, plums, beets and leguminous vegetables, and (2) the idiopathic, or essential, pentosuria. Salkowski and Jastrowitz3first described a case of essential pentosuria in a morphin addict who also occasionally excreted a trace of glucose. In this type of pentosuria, r-arabinose, an optically inactive pentose, is usually excreted. Janeway4was able to compile from the literature twenty-four of these cases up to the year 1906. In the two cases of chronic pentosuria that have come under my observation, the patients were: Mrs. A., Jewish, aged 30, who was told twelve years ago that small amounts of sugar were present in the urine. At no time has