2DFD, 4WLE, 4WLO, 4WLV, 4WLN, 4WLU, 4WLF
4191
17448
ENSG00000146701
ENSMUSG00000019179
P40926
P08249
NM_001282403NM_001282404NM_005918
NM_008617
NP_001269332NP_001269333NP_005909
NP_032643
Malate dehydrogenase, mitochondrial also known as malate dehydrogenase 2 is an enzyme that in humans is encoded by the MDH2 gene.[5]
Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria.[6]
The protein encoded by MDH2 exists as a dimer, which indicate the important connection between protein stability and enzymatic activity. Each subunit contains two structurally and functionally distinct domains. The first is the NAD-binding domain, which exists in the amino-terminal half of each molecule, and contains a parallel-sheet structure, otherwise known as a Rosman fold motif. The core dinucleotide binding structure is composed of four beta-sheets and one alpha-helix. The other domain is a carboxy-terminal domain that contains the substrate binding site and amino acids that are necessary for catalysis. The active site of these enzymes is in a cleft between two domains.[7] Crystallography reveals the dimer interface, which consists mainly of interacting alpha-helices that form a compact interaction. The active sites in these dimeric proteins are well separated from each other.[8]
Because malate dehydrogenase is closely tied to the citric acid cycle, regulation is highly dependent on TCA products.[9] Citrate also affects MDH activity by very complex manner. It inhibits the reduction of oxaloacetate under all conditions. Citrate also inhibits malate oxidation, but only at low malate or NAD concentrations. When both malate and NAD concentrations are high (10 mmol/L and 5 mmol/L, respectively), citrate can actually augment MDH2 activity.[10] All three effectors (malate, oxaloacetate and citrate) bind to the same putative allosteric site.[11] Recent studies of mitochondrial malate dehydrogenase are focused into the nature of the inactivation processes. The oligomeric structure of MDH2 has a variety of biological implications. Some researches have suggested that the dimeric structure is critical for enzymatic activity. It was first proposed that the reciprocating compulsory ordered mechanism where each subunit alternates as the active and the helper subunit, but both are needed for activity. This mechanism predicts an inactive monomer, and was corroborated by studies that showed a dramatic reduction of enzymatic activity.[12] Studies with mitochondrial MDH2 have shown that this enzyme is allosterically regulated as a complex as well. Binding experiments indicate that mitochondrial aspartate aminotransferase can associate with the alpha-ketoglutarate dehydrogenase complex and that mitochondrial malate dehydrogenase can associate with this binary complex to form a ternary complex. Formation of this ternary complex enables low levels of the alpha-ketoglutarate dehydrogenase complex, in the presence of the aminotransferase, to reverse inhibition of malate oxidation by glutamate. Thus, glutamate can react with the aminotransferase in this complex without glutamate inhibiting production of oxaloacetate by the malate dehydrogenase in the complex. The conversion of glutamate to alpha-ketoglutarate could also be facilitated because in the trienzyme complex, oxaloacetate might be directly transferred from malate dehydrogenase to the aminotransferase. In addition, association of malate dehydrogenase with these other two enzymes enhances malate dehydrogenase activity due to a marked decrease in the Km of malate. The potential ability of the aminotransferase to transfer directly alpha-ketoglutarate to the alpha-ketoglutarate dehydrogenase complex in this multienzyme system plus the ability of succinyl-CoA, a product of this transfer, to inhibit citrate synthase could play a role in preventing alpha-ketoglutarate and citrate from accumulating in high levels. This would maintain the catalytic activity of the multienzyme system because alpha-ketoglutarate and citrate allosterically inhibit malate dehydrogenase and dissociate this enzyme from the multienzyme system.[13]
Mutations in the MDH2 gene have been associated with several cancers, including uterine cancer, prostate cancer, pheochromocytoma and other paragangliomas.[14][15] In particular, MDH2 has been found to be overexpressed in doxorubicin-resistant uterine cancer cells and may contribute to drug resistance. Since MDH2 plays a major role in malate-aspartate shuttling in ATP production, its overexpression likely supplies additional energy for P-glycoprotein to pump chemotherapeutic drugs out of the cells. Likewise, MDH2 contributes to docetaxel resistance in prostate cancer cells via the JNK pathway, and its knockdown reduced ATP levels as well as increased drug sensitivity. Thus, MDH2 may be an effective therapeutic target to enhance drug treatments for cancer.[14]
العلاقات الإريترية التركية إريتريا تركيا إريتريا تركيا تعديل مصدري - تعديل العلاقات الإريترية التركية هي العلاقات الثنائية التي تجمع بين إريتريا وتركيا.[1][2][3][4][5] مقارنة بين البلدين هذه مقارنة عامة ومرجعية للدولتين: وجه المقارنة إريتر
Menara Shafer di Universitas Negara Ball Menara lonceng adalah sebuah menara berisi lonceng yang berjumlah satu atau lebih, atau seakan-akan berisi lonceng, jika memang tidak ada. Dalam tradisi Eropa, menara semacam itu paling sering dipakai di gereja dan berisi lonceng gereja. Menara lonceng modern sering berisi carillon. Menara lonceng menurut tanggal Tempat Lonceng Tua di Todaiji, Jepang (752, dibangun kembali pada 1200) Menara melingkar Irlandia, menara lonceng, di Glendalough, Irlandia, c. …
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أندريه فرانك زامبو أنغيسا معلومات شخصية الميلاد 16 نوفمبر 1995 (العمر 28 سنة)ياوندي الطول 1.84 م (6 قدم 1⁄2 بوصة) مركز اللعب وسط دفاعي الجنسية الكاميرون معلومات النادي النادي الحالي نابولي (معارًا من فولهام) الرقم 99 مسيرة الشباب سنوات فريق 2013–2014 القطن 2014–2015 ستاد ري
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У Вікіпедії є статті про інші географічні об’єкти з назвою Абердин. Місто Абердинангл. Aberdeen Прапор Координати 33°49′28″ пн. ш. 88°32′59″ зх. д. / 33.82444444447177290° пн. ш. 88.54972222224978395° зх. д. / 33.82444444447177290; -88.54972222224978395Координати: 33°49′28″ пн. ш. 88°32′59
Маковецький Олег ВолодимировичНародився 6 жовтня 1966(1966-10-06) (57 років)Чугуїв, Харківська областьКраїна СРСР РосіяМісце проживання Російська ФедераціяAlma mater Качинське вище військове авіаційне училище льотчиків Військово-повітряна академія імені Ю. О. ГагарінаВійсько…
Wulan GuritnoLahirSri Wulandari Lorraine Joko Guritno[1]14 April 1981 (umur 42)London, InggrisNama lainWulan GuritnoPekerjaanPemeranmodelpresenterpengusahaproduserTahun aktif1995—sekarang[2]Suami/istri Attila Arius Syach (m. 1998; c. 2002) Adilla Dimitri Hardjanto (m. 2009; c. 2021) Anak3, termasuk Shalom Razade Sri Wulandari Lorraine Joko Guritno, yang lebih d…
Mooses Tooth The Moose’s Tooth, Moose’s Tooth Gipfel des Mooses Tooth Höhe 3139 m Lage Alaska, USA Gebirge Alaskakette Dominanz 13,76 km → Denali (Mount Kudlich) Schartenhöhe 1005 m ↓ (2134 m) Koordinaten 62° 58′ 9″ N, 150° 36′ 48″ W62.969212-150.6133573139Koordinaten: 62° 58′ 9″ N, 150° 36′ 48″ W Topo-Karte USGS Talkeetna D-2 Mooses Tooth (Alaska) Erstbesteigung 2. Juni 1964 durch …
Pflasterstein für Maurice Desimpelaere zu Ehren seines Sieges bei Paris-Roubaix Frederic Maurice Desimpelaere (* 28. Mai 1920 in Ledegem; † 30. Januar 2005 in Wevelgem) war ein belgischer Radrennfahrer. Maurice Desimpelaere war Profi-Radrennfahrer von 1942 bis 1950. 1944 gewann er Paris–Roubaix, im Jahr darauf wurde er Fünfter. 1945 wurde er Zweiter bei der ersten Austragung von Omloop Het Volk. 1946 gewann er Quer durch Flandern und 1947 das Rennen Gent–Wevelgem, bei dem er im Jahr zuvo…
У Вікіпедії є статті про інші значення цього терміна: Як тебе не любити, Києве мій! (значення). «Як тебе не любити, Києве мій!»Пісня Юрій Гуляєв, Микола Кондратюк, Дмитро Гнатюк, Юрій Мамчук, «Барселона»Випущено 1962 (61 рік), перше публічне виконання пісні — 27 травня 1962Жа
The Transmission of the Lamp Part of a series onZen Buddhism Main articles Zen Chinese Chan Japanese Zen Korean Seon Vietnamese Thiền Zen in the United States Teachings Emptiness Bodhisattva ideal Consciousness-only Buddha-nature Buddhahood One Vehicle Zen and Sutras Doctrinal background of Zen Kenshō Satori Sudden Enlightenment Ten Ox-Herding Pictures Five ranks of Tozan Practices Zazen Six Perfections Bodhisattva vow Bodhisattva Precepts Shikantaza Sesshin Dhāraṇī Walking meditation Nia…
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← 152 153 154 → ← 150 151 152 153 154 155 156 157 158 159 → Daftar angka — Bilangan bulat ← 0 100 200 300 400 500 600 700 800 900 →Kardinalseratus lima puluh tigaOrdinalke-153(keseratus lima puluh tiga)Faktorisasi32· 17 Pembagi1, 3, 9, 17, 51, 153RomawiCLIIIBiner100110012Ternari122003Kuaternari21214Quinary11035Senary4136Oktal2318Duodesimal10912Heksadesimal9916Vigesimal7D20Basis 364936 153 (dibaca seratus lima puluh tiga) adalah sebuah angka dan sistem bilangan yang mewakil…
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First Lady of Sierra Leone since 2018 Fatima BioBio in 2022First Lady of Sierra LeoneIncumbentAssumed role 7 March 2018PresidentJulius Maada BioPreceded bySia Koroma Personal detailsBornFatima Jabbie (1980-11-27) 27 November 1980 (age 43)Koidu Town, Sierra LeoneNationalityGambianSierra LeoneanPolitical partySierra Leone People's Party (SLPP)Spouse Julius Maada Bio (m. 2013)Children4Residence(s)State Lodge, FreetownAlma mater Roehampton Institute London Col…
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Legendary bird in Middle Eastern mythology RocRoc by Edward Julius DetmoldGroupingMythologySimilar entitiesGaruda, simurgh, phoenix, thunderbirdFolkloreMiddle EasternOther name(s)RukhDetailsAir Part of a series onArabic culture ArchitectureStyles Islamic Yemeni Nabataean Umayyad Abbasid Fatimid Moorish Mamluk Features Ablaq Alfiz Arabesque Arabic dome Banna'i Gardens Girih Horseshoe arch Howz Hypostyle Islamic calligraphy Islamic geometric patterns Islamic ornament Iwan Liwan Mashrabiya Riad Mos…
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