Human erythrocyte phosphoglucomutase: comparison of the kinetic properties of PGM1 and PGM2 isoenzymes

Kinetic properties of PGM1 and PGM2 phosphoglucomutase "primary" isoenzymes from human erythrocytes were studied. The two enzyme forms share a "ping-pong" kinetic mechanism and show similar Km for substrate (glucose 1-P) and cofactor (glucose 1,6-P2). Micromolar concentrations of fructose 1,6-P2 and glycerate 2,3-P2 inhibit both PGM1 and PGM2 isoenzymes to a similar extent. The sole PGM2 form is affected by ribose monophosphates (ribose 1-P and ribose 5-P) that act as mutase inhibitors vs. glucose 1,6-P2 and as apparent activators vs. glucose 1-P. The interaction between PGM2 isoenzyme and ribose monophosphates is discussed in the light of the ability of this form to also display phosphoribomutase activity.     

The Russian gene pool. Genogeography of erythrocyte genetic markers (ACP1, PGM1, ESD, GLO1, 6-PGD)

The study continues the series of works on the Russian gene pool. Gene geographic analysis of five erythrocytic gene markers best studied in the Russian population (ACP1, PGM1, ESD, GLO1, and 6-PGD) has been performed. Gene-geographic electronic maps have been constructed for 13 alleles of these loci and their correlations with geographic latitude and longitude. For all maps, statistical characteristics are presented, including the variation range and mean gene frequencies, partial and multiple correlations with latitude and longitude, and parameters of heterozygosity and interpopulation diversity. The maps of eight alleles (ACP1*A, ACP1*C, PGM1*2+, PGM1*2-, PGM1*1-, ESD*1, GLO1*1, and PGD*C) are shown and analyzed in detail. The genetic relief and structural elements of the maps are compared with the ecumenical trends, main variation patterns of these genes in northern Eurasia, and genetic characteristics of the indigenous populations of the Urals and Europe.     

PGM1 null allele detected in a Caucasian mother-son pair

The presence of a PGM1 null allele in a mother and her son was deduced from their inconsistent phenotypes. Quantitation studies were done to confirm the half-normal enzyme activity. Phenotype analysis of 29 additional genetic markers gave no indication of non-parentage, making non-maternity a very unlikely explanation for the discrepancy.     

The Russian Gene Pool: Gene Geography of Erythrocytic Gene Markers (ACP1,PGM1,ESD,GLO1, and 6-PGD)

The study continues the series of works on the Russian gene pool. Gene geographic analysis of five erythrocytic gene markers best studied in the Russian population (ACP1, PGM1, ESD, GLO1, and6-PGD) has been performed. Gene-geographic electronic maps have been constructed for 13 alleles of these loci and their correlations with geographic latitude and longitude. For all maps, statistical characteristics are presented, including the variation range and mean gene frequencies, partial and multiple correlations with latitude and longitude, and parameters of heterozygosity and interpopulation diversity. The maps of eight alleles (ACP1*A, ACP1*C, PGM1*2+, PGM1*2–, PGM1*1–, ESD*1, GLO1*1, and PGD*C) are shown and analyzed in detail. The genetic relief and structural elements of the maps are compared with the ecumenical trends, main variation patterns of these genes in northern Eurasia, and genetic characteristics of the indigenous populations of the Urals and Europe.     

Isoelectric focusing studies of human red cell PGM1 in Japanese, with special reference to the characterization of PGM17

The distribution of phosphoglucomutase (PGM1) subtypes in human red cells was determined by isoelectric focusing in 218 Japanese samples. Nine common phenotypes were observed corresponding to the following frequencies of the four alleles at the PGM1 locus: PGM11+ 0.6560, PGM11- 0.1170, PGM12+ 0.1674 and PGM12- 0.0505. In addition, a characterization of the PGM17 allele was performed. Our results obtained in the present study revealed the possibility that the PGM17 allele may be differentiated in the two alleles of PGM17+ and PGM17- through an investigation of isoelectric focusing.     

A PGM1*1A variant with a reduced activity

An adverse homozygosity at the phosphoglucomutase-1 (PGM1) locus was detected in a family by electrophoresis on starch gels. Isoelectric focusing on polyacrylamide gels could clearly demonstrate a faint band at the same position as that of PGM1 1A in the mother and the child. Further analysis of other family samples and densitometric evaluation of the stained bands revealed the genetic transmission of a variant allele with a reduced activity. The molecular basis for the low activity is still unknown.     

Population genetics of taiga hunters and reindeer breeders in central Siberia. The biochemical markers of genes Hp, Tf, Gc, A1b, GLO1, PGM1, AcP and EsD

Biochemical markers of gene systems Alb, Tf, Gc, Hp, GLO1, PGM1, EsD, AcP were analysed in the native population of Evenc national region. It is shown that native population of Central Siberia, in spite of its mongoloid racial type, posseses the complex of gene frequencies for protein loci studied which is not typical for mongoloids. The complex may be called "central-siberian" and its origin may be connected with the process of adaptation to environment of the Central Siberian geographical region. The system of gene markers analysed may be considered as a sensitive one in the studies of processes of gene adaptation to the local environmental factors and, in this connection, being perspective in these studies among native population of Siberia.     

PGM1 and Gc subtype gene frequencies in a California Hispanic population.

The gene frequencies of the subtypes of the Gc (group-specific component) protein and PGM1 (phosphoglucomutase) enzyme systems have been determined by means of isoelectric focusing for a California Hispanic population (no. = 404). The Gc subtyping, done by immunofixation on a polyacrylamide gel, gave the following results: 1s = 0.491; 1f = 0.288; 2 = 0.218; variant = 0.0025. The PGM subtyping, done on agarose gel, gave results as follows: 1+ = 0.502; 1- = 0.266; 2+ = 0.128; 2- = 0.104. Because the gene frequencies for Hispanics in both these systems are relatively evenly balanced, the systems are of great value in Hispanic paternity investigations. The average power of exclusion is calculated to be 34.4% (Gc subtyping) and 39.8% (PGM1 subtyping).     

Isoelectric subtyping of the PGM1 in the Icelandic population

Phenotypes for the red blood cell enzyme phosphoglucomutase (PGM1) were determined by isoelectric focusing for a population of 2,501 Icelandic individuals. All ten phenotypes were observed, and the frequencies of four alleles at the PGM1 locus were as follows: PGM1 1+=0.6875; PGM1 1−=0.1124; PGM1 2+=0.1419, and PGM1 2−=0.0582. These results have been compared with those found in other northern European populations.     

Differential function of the phosphoglucomutase isozymes PGM1 and PGM2

Summary A total of 13 metabolites thought to be possibly inhibitory were tested for their influence on PGM isozyme activities, each at several different concentrations. The analysis of statistical significance was based on enzyme activities obtained by densitometric measurements of starch gels. Five of the substances were found to inhibit PGM activity, three of which definitely and a further one probably led to a significantly stronger inhibition of the isozymes of the PGM ₂ locus than of PGM ₁ isozymes. They are (1) fructose-1,6-diphosphate, (2) adenosine triphosphate, (3) citrate, and (4) possibly 2,3-diphosphoglycerate. Thus, PGM ₁ isozymes proved to function better in hard or perhaps marginal metabolic conditions. Related evolutionary aspects are discussed.     

中国人红细胞PGM(PGM位点1)多态性的等电聚焦电泳研究

用等电聚焦电泳技术对北京地区180人进行红细胞葡萄糖磷酸变位酶(PGM_1)遗传表型的分析鉴定。共检测出九个PGM_1亚型,可能由于检测样本数还不够多,目前尚未检测到PGM_1 2-亚型。根据测定结果,观察了我国人群中PGM_1亚型的分布情况,并计算出决定PGM_1亚型的四个等位基因频率为:PGM~(1+)_10617,PGM~(1-)_1 0.100,PGM~(2+)_1 0.236,PGM~(2-)_10.047。采用等电聚焦电泳可将PGM_1的个体识别能力(DP值)由用普通淀粉胶电泳分型的0.558提高到0.742。结果与世界上其他国家和地区人群相似,PGM_1在我国人群中同样是一个个体识别能力很高的多态性酶类。     

Genetic structure of the Mongols as derived from the ABO, MN, Rh, EsD, GLO1, PGM1, AcP, 6-PGD, Hp, Gc, Tf, C'3 and ChE2 loci

According to integral characterization of gene frequencies of the investigated loci AB0, MN, Rh, GLO1, PGM1, EsD, AcP, 6-PGD, Hp, Tf, Gc, C'3 and ChE2, Mongolian population has high level of polymorphism, with the exception of haplotypes R" (cdE) and Ry(CdE) at the Rh locus and TfB0-1 at the Tf locus. The data on biochemical and immunological polymorphic gene markers analysed in the population of Mongolia show that the Mongolians have some distinctive features, in comparison with the mean-in-the-world characteristics: high frequencies of the B genes at the AB0 locus; D, E, R1 and R2 at the Rh locus; GLO11, PGDc, TfDChi, E2(C5+), PGM1(1+); low frequencies of the genes A(AB0), R0(Rh), AcPc, Hp1, Gc2, C'3F, PGM 1(2-); the rest of the genes at the above-mentioned loci and the genes of the locus MN have the mean-in-the-world frequencies.     

Description and genetics of glucose phosphate isomerase (GPI) and phosphoglucomutase (PGM) polymorphisms in Asellus aquaticus (L.)

Analysis of Western European populations of Asellus aquaticus uncovered 10 electrophoretic phenotypes of glucose phosphate isomerase (GPI) and 7 of phosphoglucomutase (PGM). Breeding studies indicate that the variation is controlled by codominant alleles at two autosomal loci. Genotype frequencies in the two sexes do not differ significantly, mating between genotypes is random, and no structural linkage is detectable between the two loci. PGM shows nongenetic, "secondary" banding, particularly in animals stored at -20 degrees C prior to electrophoresis. This secondary banding confounds the identification of the genetic variation but can be controlled by the reducing agent 2-mercaptoethanol.     

中国20个民族中PGM_1及其亚型EsD、GLO1、AK、ADA和6-PGD酶型分布调查

调查了汉族、鄂伦春、赫哲、朝鲜、蒙古、羌、土家、苗、侗、畲、壮、纳西、傈僳、白、彝、景颇、哈尼、傣、维吾尔和塔吉克等20个民族的PGM_1及其亚型,EsD、GLO_1、AK、ADA和6-PGD等酶型的分布及基因频率。PGM_1及其亚型、EsD和GLO_1在中国各民族中是分布较好的,个人识别能力较高的酶。有12个民族查出有PQM_1~6基因,壮族的频率最高,PGM_1 6-1表型达4.15％。对在4174份血样中所检出的带有PGM_1~6基因的68份血样做亚型分析,在凝胶上PGM_1~6谱带均在同一位置上。EsD_1基因频率的总趋向是北方各民族高于南方。哈尼、傈僳、傣、纳西、畲、壮、侗和苗等民族EsD2-2表型达15％以上,哈尼族高达32.4％。GLO1~1基因频率塔吉克和维吾尔族为0.2927和0.2112,羌族为0.0583,其它各族在0.0714—0.1527。各民族AK~1、ADA和6-PGD~(?)基因频率均甚高。     

Estimating blood phenotype probabilities and their products.

We consider two methods of estimating phenotype probabilities for a number of standard genetic markers like the ABO, MNSs, and PGM markers. The first method is based on the maximum likelihood estimates of the allele probabilities, and the second (multinomial) method uses the phenotype proportions in the sample. The latter is easy to use, the estimates are always unbiased, and simple formulae for variances are available. The former method, although giving more efficient estimates, requires the assumption of panmixia so that the Hardy-Weinberg law can be used. The two methods are compared theoretically, where possible, or by simulation. Under panmixia, the maximum likelihood estimates can be substantially more efficient than the multinomial estimates. The estimates are also compared in the codominant allele case for nonpanmictic populations. The question of efficiency is of importance when estimating the probability of obtaining a given set of phenotypes, i.e., the product of individual phenotype estimators. This problem is discussed briefly.     

Antitumor and antimetastatic activity of the immunoadjuvant peptidoglycan monomer PGM in mice bearing MCa mammary carcinoma

Summary The antitumor and antimetastatic activities of the water-soluble peptidoglycan monomer GlnNAc-Mur-NAc-L-Ala-D-iso-Gln-meso-diamminopimelic acid (-NH₂)-D-Ala-D-Ala (PGM), which has immunostimulant effects, have been evaluated in CBA mice bearing MCa mammary carcinoma. The antineoplastic effects of PGM depend strictly on the dosage and treatment schedule used. Though a significant inhibition of the primary tumor growth is observed over a wide range of dosage, only the IV administration of daily doses of 50 mg/kg/day on days 1, 5, 10, 15 inhibits spontaneous lung metastasis formation and in parallel prolongs the survival time of the treated mice. The magnitude of the antimetastatic effects of PGM depends on the degree of dissemination of the tumor, and is greater when the number of metastatic foci is low. Examination of the therapeutic potential of PGM in combination with surgery has further indicated that the timing of administration plays an important role in the overall effectiveness of this substance. A 5-day interval is necessary between two consecutive injections for the induction of significant increases of the survival times.     

6PGD and PGM1 polymorphisms in south Sardinia

A sample of unrelated individuals, born and living in South Sardinia, was studied with respect to the enzymes 6PGD and PGM1. The gene frequencies were: PGDA 0.989 and PGM1 0.790. The results were compared with those of other Italian populations.     

GPT, 6-PGD,PGM and AK phenotyping inone starch gel

Summary A method is described for simultaneous electrophoretic separation of GPT (EC 2.6.1.2), 6-PGD (EC 1.1.1.44), PGM (EC 2.7.5.1) and AK (EC 2.7.4.3) enzyme variants.

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Zusammenfassung Beschreibung einer Methode zur gleichzeitigen elektrophoretischen Auftrennung der Enzymvarianten von GPT (EC 2.6.1.2), 6-PGD (EC 1.1.1.44), PGM (EC 2.7.5.1) and AK (EC 2.7.4.3).

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Abbreviations GPT Glutamic Pyruvic Transaminase - 6-PGD 6-Phosphogluconate Dehydrogenase - PGM Phosphoglucomutase - AK Adenylate Kinase Supported by the Deutsche Forschungsgemeinschaft, the Stiftung Volkswagenwerk and the Fonds der Chemischen Industrie.     

我国几个民族中毛发根葡糖磷酸变位酶—1的亚型分布

本文报道了利用等电聚焦的方法,从毛发根鞘细胞分析了我国汉、苗、土家、撒拉、土、达斡尔和赫哲等民族的葡糖磷酸变位酶-1(PGM_1)10亚型的分布,并且与其他人群的基因频率作了比较。     

Subtyping of human red cell phosphoglucomutase locus 1 (PGM1) polymorphism: a third PGM1(1) allele common among Twa Pygmies from North Rwanda.

Seventy-eight Twa Pygmies from North Rwanda have been subtyped by acid starch gel electrophoresis for the polymorphism at the phosphoglucomutase locus 1 (PGM1). A third common PGM1(1) allele that has been named PGM1(1Twa) was detected in heterozygous association with both PGM1(1S) and PGM1(1F) alleles. The PGM1(1Twa) product is faster than those of the other two PGM1(1) alleles and has the same electrophoretic mobility as the rare PGM1(6) enzyme. The frequency of PGM1(1Twa) was found to be 0.45.