Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria is an intracellular double membrane-bound structure and it can provide energy for intracellular metabolism. The metabolism includes Krebs cycle, beta-oxidation and lipid synthesis. The density of mitochondria is different in various tissues dependent upon the demands of oxidative phosphorylation. Mitochondrial diseases can occur by defects either in mitochondrial DNA or nuclear DNA. Human mitochondrial DNA (mtDNA) encoding for 22 tRNAs, 2 rRNAs and 13 mRNAs that are translated in the mitochondria. Mitochondrial genetic diseases are most resulted from defects in the mtDNA which may be point mutations, deletions, or mitochondrial DNA depletion. These patterns of inheritance in mitochondrial diseases include sporadic, maternally inherited, or of Mendelian inheritance. Mitochondrial DNA depletion is caused by defects in the nuclear genes that are responsible for maintenance of integrity of mtDNA or deoxyribonucelotide pools and mtDNA biogenesis. The mtDNA depletion syndrome (MDS) includes the following categories: progressive external ophthalmoplegia (PEO), predominant myopathy, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), sensory-ataxic neuropathy, dysarthria, and ophthalmoplegia (SANDO) and hepato-encephalopathy. The most common tissues or organs involved in MDS and related disorders include the brain, liver and muscles. These involved genes are divided into two groups including 1) DNA polymerase gamma (POLG, POLG2) and Twinkle genes whose products function directly at the mtDNA replication fork, and 2) adenine nucleotide translocator 1, thymidine phosphorylase, thymidine kinase 2, deoxyguanosine kinase, ADP-forming succinyl-CoA synthetase ligase, MPV17 whose products supply the mitochondria with deoxyribonucleotide triphosphate pools needed for mtDNA replication, and possible mutation in the RRM2B gene. The development has provided new information about the importance of the biosynthetic pathway of the nucleotides for mtDNA replication. Further investigation on the understatanding between the nuclear and mitochondrial genomes is expected.
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PMID:[Mitochondrial disease and mitochondrial DNA depletion syndromes]. 2032 99

White matter involvement has recently been recognized as a common feature in patients with multisystem mitochondrial disorders that may be caused by molecular defects in either the mitochondrial genome or the nuclear genes. It was first realized in classical mitochondrial syndromes associated with mitochondrial DNA (mtDNA) mutations, such as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), Leigh's disease, and Kearns-Sayre's syndrome. Deficiencies in respiratory chain complexes I, II, IV, and V often cause Leigh's disease; most of them are due to nuclear defects that may lead to severe early-onset leukoencephalopathies. Defects in a group of nuclear genes involved in the maintenance of mtDNA integrity may also affect the white matter; for example, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) caused by thymidine phosphorylase deficiency, Navajo neurohepatopathy (NNH) due to MPV17 mutations, and Alpers syndrome due to defects in DNA polymerase gamma (POLG). More recently, leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) has been reported to be caused by autosomal recessive mutations in a mitochondrial aspartyl-tRNA synthetase, DARS2 gene. A patient with leukoencephalopathy and neurologic complications in addition to a multisystem involvement warrants a complete evaluation for mitochondrial disorders. A definite diagnosis may be achieved by molecular analysis of candidate genes based on the biochemical, clinical, and imaging results.
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PMID:Mitochondrial syndromes with leukoencephalopathies. 2242 7