Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most chromosome aberrations in gliomas are numerical, resulting in either gains or deficiencies of whole chromosomes. In tumors of low malignancy, the karyotype is frequently normal or exhibits a loss of sex chromosome and a gain of chromosome 7. These two anomalies may not be directly related to malignancy. In the highly malignant cases, the two most frequent aberrations are the gain of chromosome 7 and the loss of chromosome 10, other anomalies such as losses or deletions of chromosomes, 9, 22, 6, 13 and 14 being detected at various frequencies. Several of these chromosomes carry important genes of adenine metabolism: AK1 and AK3 (adenylate kinase) and MTAP (methylthioadenosine phosphorylase) for chromosome 9; ADK (adenosine kinase) and mitochondrial ATPase for chromosome 10; ADSL (adenylosuccinate lyase) for chromosome 22, NP (nucleoside phosphorylase) for chromosome 14. We performed the corresponding assays of enzyme activity on both fresh tumors and tumors grafted on nude mice, which showed that these enzymes had a relatively low activity although the tumors were proliferating. However, chromosome losses do not seem to directly cause the metabolic alterations by gene dosage effect. Interestingly, chromosome 10, frequently deficient, also carries genes of importance for glycolysis (hexokinase) and glutamate metabolism (glutamate dehydrogenase and glutamate oxaloacetate transaminase). The deficiency for these genes could be taken into account for a better type of chemotherapy by antimetabolics.
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PMID:[Chromosome abnormalities and adenine metabolism in human glial tumors]. 144 60

We have used SWATH mass spectrometry to quantify 3648 proteins across 76 proteomes collected from genetically diverse BXD mouse strains in two fractions (mitochondria and total cell) from five tissues: liver, quadriceps, heart, brain, and brown adipose (BAT). Across tissues, expression covariation between genes' proteins and transcripts-measured in the same individuals-broadly aligned. Covariation was however far stronger in certain subsets than others: only 8% of transcripts in the lowest expression and variance quintile covaried with their protein, in contrast to 65% of transcripts in the highest quintiles. Key functional differences among the 3648 genes were also observed across tissues, with electron transport chain (ETC) genes particularly investigated. ETC complex proteins covary and form strong gene networks according to tissue, but their equivalent transcripts do not. Certain physiological consequences, such as the depletion of ATP synthase in BAT, are thus obscured in transcript data. Lastly, we compared the quantitative proteomic measurements between the total cell and mitochondrial fractions for the five tissues. The resulting enrichment score highlighted several hundred proteins which were strongly enriched in mitochondria, which included several dozen proteins were not reported in literature to be mitochondrially localized. Four of these candidates were selected for biochemical validation, where we found MTAP, SOAT2, and IMPDH2 to be localized inside the mitochondria, whereas ABCC6 was in the mitochondria-associated membrane. These findings demonstrate the synergies of a multi-omics approach to study complex metabolic processes, and this provides a resource for further discovery and analysis of proteoforms, modified proteins, and protein localization.
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PMID:Quantifying and Localizing the Mitochondrial Proteome Across Five Tissues in A Mouse Population. 2994 35