Explore chapters and articles related to this topic
Hyperornithinemia, hyperammonemia, homocitrullinuria syndrome
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The ornithine transporter gene SIC25A15, which was called ORNT1, was identified by the use of sequences from the ARG 11 and ARG 13 genes of Neurospora and Saccharomyces which encode the mitochondrial carrier family proteins that are involved in the transport of ornithine across the mitochondrial inner membrane [9]. The expression of ORNT1 is high in the liver. Expression of ORNT1 in transformed fibroblasts of patients with HHH syndrome restored ornithine transport function. The gene contains seven exons over 23 kb [8]. It encodes a 301 amino acid protein. A 4.2-kb mRNA transcript is expressed in liver and pancreas. The gene was mapped to chromosome 13q14.11 [8, 9].
Roles of Daily Diet and Beta-Adrenergic System in the Treatment of Obesity and Diabetes
Published in Nilanjana Maulik, Personalized Nutrition as Medical Therapy for High-Risk Diseases, 2020
Ebru Arioglu Inan, Belma Turan
The β3-AR agonist treatment resulted in weight loss in obese mice without a reduction in food intake (Yoshida, Sakane et al. 1994) which has been attributed to increased thermogenesis in brown adipose tissue (Himms-Hagen, Cui et al. 1994). This effect could be related to stimulation of UCP1 (Inokuma, Okamatsu-Ogura et al. 2006). UCP-1 is a mitochondrial carrier protein in brown adipose tissue and has a role in energy consumption as heat. The lipolytic effects of β3-AR, on the other hand, involve mobilization of fat as free fatty acids from white adipose tissue deposits which are oxidized and used in thermogenesis in brown adipose tissue (Ursino, Vasina et al. 2009). Predisposition to abdominal obesity, it has been suggested, is associated with the presence of the Arg64 allele in the first intracellular loop of β3-ARs gene which could further lead to insulin resistance (Widen, Lehto et al. 1995). Moreover, a Trp64 Arg mutation of β3-AR has been found to be related to the early onset of type 2 diabetes in obese Pima North American Indians (Walston, Silver et al. 1995). This mutation is also associated with mild gestational diabetes (Festa, Krugluger et al. 1999).
Structure, Function and Evolutionary Aspects of Mitochondria
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Puja Agarwal, Mehali Mitra, Sujit Roy
Evolutionarily, the origin of the mitochondrial protein import machinery and the mitochondrial envelope are most important changes in organellogenesis. One scenario proposes that first the evolution of mitochondrial protein import machinery happened to insert solute carriers into the proto-mitochondrial inner membrane (Smith, 2006, 2009). These carriers took part in the movement of small molecules such as nucleotides (ATP, ADP), anionic metabolites, amino acids and inorganic ions across the mitochondrial inner membrane. Many inner membrane transporters belongs to eukaryotic “mitochondrial carrier family’ (MCFs) which may have originated from a single ancestral carrier that was inserted into the inner membrane of the protomitochondria (Amiri et al., 2003; Andersson et al., 2003; Smith, 2006). Another general view instead suggests that the protein transport machinery evolution took place to insert host proteins into the outer membrane of the proto-mitochondria (Gross and Bhattacharya, 2011). If the latter theory was true, the evolution of the protein import machinery remained advantageous and had happened to gain control over the biogenesis of the proto-mitochondrial endosymbiont envelope.
Establishing molecular signatures of stroke focusing on omic approaches: a narrative review
Published in International Journal of Neuroscience, 2020
Abhilash Ludhiadch, Kanika Vasudeva, Anjana Munshi
Using i-TRAQ based 2 D LC MS/MS technique, Datta et al. (2013) conducted a study on autopsied human female brain to determine the expression of proteins related to glycolysis, pyruvate dehydrogenase, TCA cycle and oxidative phosphorylation in IS. They found a deregulation in MAS (maltate- aspartate shuttle) and participating proteins SLC25A11, calcium binding mitochondrial carrier protein Aralar 1 (SLC25A12), GOT2 and MDH2 (maltate dehydrogenase 2) which leads to failure of energy metabolism. An increased levels of some other proteins including VIM (vimentin), GFAP (glial fibrillary acidic protein), anti-inflammatory proteins (ANXA1, ANXA2) and iron storage protein ferritin (FTH1, FTL) were also observed. This study suggested that these deregulated proteins might be potential biomarkers for ischemic stroke [75].
Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag
Published in Platelets, 2020
Jesús María Hernández-Sánchez, José María Bastida, Diego Alonso-López, Rocío Benito, José Ramón González-Porras, Javier De Las Rivas, Jesús María Hernández Rivas, Ana Eugenia Rodríguez-Vicente
A deregulation in genes involved in erythropoiesis has been recently described after the therapy with recombinant human erythropoietin [56]. SLC4A1 encodes an anion exchanger family member expressed in the erythrocyte plasma membrane and strongly induced during erythroid maturation, being reported that chromatin around the promoter and 3´ end of SLC4A1 is only available during erythroid differentiation [57]. SLC25A39, a member of the SLC25 transporter or mitochondrial carrier family of proteins, is required for normal heme biosynthesis and may play a role in iron homeostasis [58]. These results would be in agreement with the GEP obtained in our study, suggesting that in non-responder patients the erythropoiesis could be highly up-regulated. Interestingly, our work shows that several genes involved in the heme pathway were activated in non-responder patients (ES = 0.79, NES = 3.56 and FDR q-value <0.0001) (Supplementary Figure S3).
MSDC-0602K, a metabolic modulator directed at the core pathology of non-alcoholic steatohepatitis
Published in Expert Opinion on Investigational Drugs, 2018
Jerry R. Colca, William G McDonald, Wade J. Adams
All first generation, TZDs that are active as ‘insulin sensitizers’ have been shown to directly dampen the entry of pyruvate through the mitochondrial carrier [18], but these compounds differ greatly in their ability to directly bind to and activate the PPARγ transcription factor, an action that is known to produce dose-limiting side effects and which has limited the discovery of new agents [19]. Given this new understanding of this recently identified mitochondrial target with a functional connection to nutrient overload, a new generation of TZDs is being studied that have limited ability to directly bind to and activate PPARγ, yet maintain the ability to modulate MPC [20].