T Kanno, K Sudo, M Kitamura, S Miwa, A Ichiyama, Y Nishimura
{"title":"Lactate dehydrogenase A-subunit and B-subunit deficiencies: comparison of the physiological roles of LDH isozymes.","authors":"T Kanno, K Sudo, M Kitamura, S Miwa, A Ichiyama, Y Nishimura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Different clinical features exist for lactate dehydrogenase A-subunit and B-subunit deficiencies. The metabolic basis for these clinical differences was elucidated by investigating carbohydrate metabolism in the affected tissues. Glycolysis was markedly retarded at the position of glyceraldehyde 3-phosphate dehydrogenase, and significant increases of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-diphosphate were observed. The physical and kinetic properties of glyceraldehyde 3-phosphate dehydrogenase prepared from human erythrocytes and skeletal muscle were almost identical, but the mode of inhibition of the enzyme was slightly different in erythrocytes and in skeletal muscle. In erythrocytes, impaired reoxidation of NADH followed by the deficiency of substrate NAD+ causes a reduction of glyceraldehyde 3-phosphate dehydrogenase activity. However, in skeletal muscle, the increased level of NADH markedly inhibits the enzyme under anaerobic conditions. A flux of triose phosphates from glycolysis occurred in skeletal muscle of a patient with A-subunit deficiency. This flux is attributable to the high cytosol alpha-glycerophosphate dehydrogenase activity in skeletal muscle. for these reasons the ATP production was significantly impaired in the patient and the damage to muscle cells brings about the release of cytosolic enzymes and muscle rigidity after hard exercise. In contrast in the erythrocytes, the level of alpha-glycerophosphate dehydrogenase is very low and another red cell-specific NADH reoxidizing system such as NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) is operating. In this manner, the NAD+ level in erythrocytes is compensated for without the flux of triose phosphates derived from glucose. Therefore, the ATP production in erythrocytes is sufficiently maintained by glycolysis even in a patient with complete lactate dehydrogenase B-subunit deficiency. Thus, impaired ATP production in anaerobic stage is a condition which is specific for lactate dehydrogenase A-subunit deficiency but does not occur for B-subunit deficiency. The different clinical features of the A- and B-subunit deficiencies have been clearly elucidated.</p>","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"7 ","pages":"131-50"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17470791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of RNA polymerase I by phosphorylation and production of anti-RNA polymerase I antibodies in rheumatic autoimmune diseases.","authors":"S T Jacob, D A Stetler, K M Rose","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Relative to resting liver, Morris hepatomas with different growth rates (3924A, 5123D, 7800, and 7777) all had higher (two to eightfold) levels (activity/gm tissue) of RNA polymerase I. Only the most rapidly growing tumor (hepatoma 3924A) showed a substantial increase (fivefold) in RNA polymerase III activity. RNA polymerase II activity/gm tissue in the hepatomas was similar to that in resting liver. The elevation in the hepatoma RNA polymerase I activity resulted from both an increase in the number of transcriptionally active enzyme molecules and an increase in the specific activity of the enzyme as a result of phosphorylation. Phosphorylation of RNA polymerase I from Morris hepatoma 3924A could be catalyzed either by an endogenous protein kinase or by a highly purified preparation of NII protein kinase from the same tumor. Three out of eight polypeptides (Mr 120,000, 65,000, and 25,000) or RNA polymerase I were phosphorylated. Phosphorylation resulted in enhanced RNA synthesis at the level of chain elongation. Another nuclear protein kinase, NI, had no significant effect on RNA polymerase I. The activity and/or amount of the NII protein kinase was significantly reduced in resting liver, which correlated with decreased specific activity of the liver RNA polymerase I. Anti-RNA polymerase I antibodies were found in the sera of patients with rheumatic autoimmune diseases such as systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Sera from these patients were capable of specifically inhibiting RNA polymerase I activity in vitro. Antibodies were produced predominantly against three of the polypeptides--S3 (Mr 65,000), S4 (Mr 42,000), and S5 (Mr 25,000) of RNA polymerase I. The spectrum and proportion of the antibodies against these three subunits differ with each patient and with the type of the autoimmune disease. These observations indicate that (1) the NII kinase can regulate RNA polymerase I activity, (2) protein kinase NII is associated with the polymerase I enzyme complex, and (3) certain polypeptides of this enzyme complex may be the target antigens in rheumatic autoimmune disease.</p>","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"7 ","pages":"263-75"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17659831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The genetic and epigenetic control of sn-glycerol-3-phosphate dehydrogenase isozyme expression during the development of Drosophila melanogaster.","authors":"G C Bewley","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"9 ","pages":"33-62"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17473536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The use of enzyme kinetics to predict differences in cellular metabolism, developmental rate, and swimming performance between LDH-B genotypes of the fish, fundulus heteroclitus.","authors":"D A Powers, L DiMichele, A R Place","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In summary, the LDH-B4 allelic isozymes of F heteroclitus are functionally nonequivalent. The kinetic differences observed can be explained by a greater catalytic efficiency by LDH-B4b at colder temperatures than LDH-Ba4. The situation appears to be reversed at higher temperatures. The LDH-BaBb allelic isozymes is not exactly intermediate to the two homotetramers. These in vitro functional differences can be interpreted as being useful to individuals with specific LDH-B phenotypes. Moreover, predictions concerning their significance at the metabolic and/or whole organism level can be made and tested experimentally. We have found both developmental and physiological differences between LDH-B phenotypes that appear to depend on a significant variation in ATP metabolism between the phenotypes. Although we have not elucidated the mechanism by which ATP metabolism is affected, we have shown that the pattern of ATP differences between phenotypes, corresponds precisely with the pattern of kinetic differences between the LDH-B allelic isozymes. The resolution of the evolutionary significance of these phenomena and their underlying molecular mechanism will shed light on the controversy between exponents of the selectionist and neutralist schools of thought.</p>","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"10 ","pages":"147-70"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17414954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic and epigenetic control of the pyruvate kinase isozymes in mammals.","authors":"J Marie, M J Levin, M P Simon, A Kahn","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In man, patients with hereditary red cell pyruvate kinase (PK) deficiency have their enzyme concomitantly affected in both red cells and liver (PK-L), such that red cell L' and liver L PK subunits appear to be encoded by the same structural gene. Very recently, a mutant M1 PK has been described in muscle from a special mouse strain in which the M2 PK was concomitantly modified. Thus, it has been suggested that the M1 and M2 PK subunits are also encoded by the same structural gene, a gene distinct from that encoding L' and L. In this paper, we show that synthesis of each of the four PK subunits is specified by a different specific mRNA. Two structural genes, but at least four different mRNAs seem therefore to control synthesis of the PK isozymes. Genetic and epigenetic mechanisms responsible for generation of this diversity at the RNA level are discussed. In addition to these mechanisms of PK diversity, some PK subunits can be modified by post-translational events. In red cells, for instance, cell aging is associated with a progressive, partial proteolysis of the C-terminal extremities of L' subunits, ultimately resulting in cleavage of the phosphorylatable site.</p>","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"7 ","pages":"221-40"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17935746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isozyme assessment of plant genetic resources.","authors":"A H Brown, M T Clegg","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The genetic resources of cultivated plants consist of the genetic diversity present among developed cultivars, in the land races or primitive stocks, and in wild populations of their evolutionary relatives. Genetic evaluation of these resources through isozyme studies provides an important aid in efficient collection, storage, and use. Recent isozyme studies with barley exemplify these points. The allelic isozyme diversity present in 12 land race samples from Iran has been compared with that found in cultivars on the one hand, and natural populations of wild barley (H spontaneum) on the other. The primitive materials were on average more variable than the cultivars but less variable than the wild populations, supporting the view that the land races are or crucial importance in genetic conservation. Some roles for isozyme data in the manipulation of genetic resources have been outlined.</p>","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"11 ","pages":"285-95"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17698211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isozymes as probes and participants in developmental and evolutionary genetics.","authors":"G S Whitt","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"10 ","pages":"1-40"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17414952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isozyme monitoring of genetic variation in Lycopersicon.","authors":"C M Rick, S D Tanksley","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Linkages with isozymic loci facilitate the investigation of certain classes of genetic variation. Due to the mapping of 20 isozymic loci on nine of the 12 chromosomes of the cultivated tomato (Lycopersicon esculentum), much progress has been made in these applications, particularly in the analysis of interspecific hybrids. Isozymes can expedite the selective elimination of inferior wild parent germ plasm in backcross transfer of desired genes to the cultivated parent. Allelic isozyme constitution also aids in identification of lines, particularly in evaluating the purity of F1 hybrid cultivars. Advantages that isozymes impart to such investigations are: (1) unequivocal classification of phenotypes, (2) detection of heterozygotes, (3) lack of epistasis between isozyme loci, (4) lack of effect of allelic isozymes per se on morphology or physiology, (5) prolific source of monogenic markers, and (6) phenotyping at early developmental stages. Each of these attributes can be exploited to great advantage, but collectively they constitute a formidable argument for monitoring genetic variation by means of isozymes. Linkages between isozyme loci and qualitative loci can be exploited as in the monitoring of Mi (gene for root-knot nematode resistance derived from L peruvianum) by the very tightly linked Aps-1(1); in similar fashion, Prx-2(1) serves as a useful marker for ms-10 (male sterility). Asp-1 monitoring in the former is more reliable than testing for nematode resistance per se; codominance of Prx-2 alleles of the latter solves problems incurred by the recessiveness of ms-10; in both instances phenotypes can be ascertained at earlier growth stages for isozymes than for economic traits. In the first backcross of the interspecific hybrid L esculentum x Solanum pennellii to the former, the segregation of four quantitative traits was monitored by allelic isozymes at 12 loci, situated on at least eight chromosomes, covering approximately 60% of the known tomato genome. At least five quantitative trait loci (QTL) were found to determine each of the four traits. Each parent contributes alleles with positive as well as negative effects, the greatest balance for stigma exsertion, the trait also exhibiting the greatest extent of transgressive segregation. Three pairs of linked isozymic loci permitted a crude form of three-point mapping of the associated QTL. interactions between QTL linked with pairs of isozymic genes were tested in all possible combinations; 18 of the 274 comparisons showed significant interactions, indicating epistasis.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"11 ","pages":"269-84"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17698210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liver-specific enzymes in human fibroblast x rat hepatoma somatic cell hybrids.","authors":"C Kielty, S Povey","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77729,"journal":{"name":"Isozymes","volume":"9 ","pages":"163-77"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17413408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}