Pyruvate carboxylase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Pyruvate carboxylase (EC 6.4.1.1) is a biotin-containing mitochondrial enzyme, which catalyzes the conversion of pyruvate to oxalacetate by CO2 fixation (Figure 48.1) [1, 2]. As in the case of other carboxylases, the reaction mechanism is a two-step process in which biotin is first carboxylated and then the carboxyl group is transferred to the acceptor, pyruvate [3, 4]. There is a separate catalytic site for each of the two steps. The enzyme is a tetramer of 500 kDa whose individual equal-sized protomers have a different structure from other biotin-containing carboxylases [5], but the highly conserved amino acid sequence at the biotin site of biotin-containing carboxylases, Ala-Met-Lys-Met is present in pyruvate carboxylase [6]. The biotin is linked to the ε amino group of the lysine.
Diseased States in Man and Other Vertebrates
D. B. Keech, J. C. Wallace in Pyruvate Carboxylase, 2018
Robinson et al.693 observed that the incubation of biotin-depleted cultured fibro-blasts obtained from two patients with Type A BRMCD in the presence of [3H] biotin leads to the incorporation of some [3H] biotin into the band corresponding to the pyruvate carboxylase subunit (cell lines 965 and 985 in Figure 2). Some labeling of methylcrotonyl- and propionyl-CoA carboxylase was also observed, but this was weaker than that found for these enzymes in normal fibroblasts. These results suggest that in the cells of the two patients the addition of biotin to at least two biotin-dependent carboxylase enzymes is impaired. Quantitative measurements and comparison of rates of [3H] biotin incorporation will be required to confirm this.
Anatomy, Biochemistry and Physiology
Massimo Maffei in Vetiveria, 2002
The primary carboxylation reaction, common to all three variants, occurs in the cytosol of the mesophyll cells and is catalysed by phosphoenolpyruvate carboxylase (PEP-case), using HCO3− rather than CO2 as a substrate. The fate of the oxaloacetate produced in this reaction depends on the C4 variant (Gutierrez et al., 1974). In the NADP-ME type, oxaloacetate is reduced to malate in the mesophyll chloroplasts, then transported to the bundle sheath cell chloroplasts and decarboxylated by NADP-ME enzyme. In the NAD-ME and PCK species, oxaloacetate undergoes transamination in the cytosol with glutamate as amino donor. The aspartate is transported into the bundle sheath cells and reconverted to oxaloacetate by transamination in the mitochondria (NAD-ME species) or the cytosol (PCK species). Without changing compartmentalization, the oxaloacetate is reduced and then decarboxylated by NAD-ME in NAD-ME species, while in PCK species oxaloacetate is decarboxylated by PCK. In NADP-ME plants, the C3 acid transported back to the mesophyll is pyruvic acid as pyruvate but in NAD-ME and PCK species alanine is probably converted to pyruvate in the mesophyll cell cytosol. The final reaction of the C4 pathway, which is common to all three variants, is the conversion of pyruvate to phosphoenolpyruvate within the mesophyll chloroplasts (Maffei, 1999).
Characterization of planktonic and biofilm cells from two filamentous cyanobacteria using a shotgun proteomic approach
Published in Biofouling, 2020
Maria João Leal Romeu, Dany Domínguez-Pérez, Daniela Almeida, João Morais, Alexandre Campos, Vítor Vasconcelos, Filipe J. M. Mergulhão
Moreover, for both cyanobacterial strains, in biofilms formed on perspex and at 4 s−1 a protein involved in the formation of the carboxysome (carbon dioxide-concentrating mechanism protein CcmK) was also found. Carboxysomes are polyhedral inclusion where the ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco; the central enzyme in photosynthetic carbon assimilation) is sequestered. The CO2 concentrating mechanism (CCM) is an adaptive and effective strategy evolved in cyanobacteria and also in eukaryotic microalgae for carbon acquisition, and it enables these organisms to survive when the CO2 concentration limits photosynthesis (Wang et al. 2015). Baba et al. (2011) also studied this mechanism in the unicellular green alga Chlamydomonas reinhardtii. When the CO2 concentration was elevated from the ambient air level to 3%, the algal growth rate increased 1.5-fold, and the amount and the composition of extracellular proteins clearly changed. However, significant changes were not found in intracellular proteins (Baba et al. 2011). In a study performed by Slabas et al. (2006), a decrease in Rubisco proteins was observed after heat shock in Synechocystis PCC 6803. Moreover, the CCM is a fundamental aspect of photosynthesis, metabolism, growth and biomass production in photosynthetic organisms and understanding this process provides guidance for potential molecular manipulation to improve biomass yield for commercial applications (Badger and Price 2003).
Effect of perinatal biotin deficiency on auditory pathway of the Wistar-Albino rats
Published in Acta Oto-Laryngologica, 2019
Nevreste Didem Sonbay Yılmaz, Özer Erdem Gür, Nuray Ensari, Erdogan Bulut, Ozlem Tugce Kaya, Serap Sırvancı, Betul Danısman, Narin Derin, Bahri Gezgin, Nurdan Aygener, Mustafa Deniz Yılmaz
Biotin binds to carboxylase enzyme with the “halocarboxylase synthesis” enzyme. In the proteolytic destruction after entering into metabolic reaction, the biotin content of carboxylase is expressed as biocytin (ε-Biotinoyl-L-Lysine) or biotinylated peptides [6,7]. Biocytin also forms during the digestion of food. By destroying the amide bonds in the body, biotinase enzyme frees the biotin and the freed biotin again participates in carboxylase activity. This is known as the biotin cycle [2,3,6]. The biotin required for metabolism for biotin synthesis in mammals is primarily obtained from the biotin cycle and expressed with biotin obtained from the diet [3]. At times when there is an increased requirement for biotin such as pregnancy in particular, during lactation, or excessive physical activity, the metabolism needs supplementary biotin due to increased biotin deficiency and this need is met by the diet [2].
The role of diet in multiple sclerosis: A review
Published in Nutritional Neuroscience, 2018
Sabrina Esposito, Simona Bonavita, Maddalena Sparaco, Antonio Gallo, Gioacchino Tedeschi
Biotin (vitamin H) is widely distributed in natural foodstuffs (especially in liver, egg yolk, and cow's milk), with a recommended daily intake of 30 μg in adults. Biotin serves as a coenzyme in carboxylation reactions involved in energy metabolic pathways.165 The results of an open-label pilot study169 suggested that high doses (300 mg/day) of biotin, administered for a mean duration of 9.2 months, might exert benefits on disability progression in MS. Treatment efficacy was evaluated on progressive MS patients by assessing changes in EDSS, Timed 25-foot walk (TW25) test, walking distance, muscle strength, and videotaped clinical examination (in 18 patients with spinal cord damage); visual acuity, Goldmann perimetry, visual evoked potentials, and Humphrey automated perimetry (in five patients with prominent visual involvement). Due to the small sample size, results were reported for each parameter in each single patient; over 90% of participants exhibited some significant benefit (qualitative or quantitative) on clinical and/or electrophysiological examinations after high-dose biotin treatment. Fatigue, swallowing difficulty, and urinary dysfunction improved in 5, 4, and 2, patients respectively. Positive results were also reported in a randomized, double-blind, placebo-controlled trial170 where 154 patients with spinal progressive MS, and no evidence of clinical–radiological disease activity, showed significant decrease in EDSS score or ≥20% improvement in TW25, after 12 months of treatment with high doses of biotin.
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