6. Metabolic pathways and enzyme evolution

Author(s):  
Paul Engel

‘Metabolic pathways and enzyme evolution’ focuses on metabolic pathways and enzyme evolution. Although a few enzymes catalyse a single isolated reaction, most are part of a team that catalyses a series of reactions in which each enzyme picks up its predecessor’s product, taking it a step further to create a metabolic pathway. This pathway may be to build up, say, an amino acid from simpler starting molecules, or conversely to break down food molecules to yield new chemical building blocks and sometimes also to trap useable energy. Life is the combined outcome of this seemingly logical enzyme teamwork.

2020 ◽  
Vol 15 ◽  
Author(s):  
Affan Alim ◽  
Abdul Rafay ◽  
Imran Naseem

Background: Proteins contribute significantly in every task of cellular life. Their functions encompass the building and repairing of tissues in human bodies and other organisms. Hence they are the building blocks of bones, muscles, cartilage, skin, and blood. Similarly, antifreeze proteins are of prime significance for organisms that live in very cold areas. With the help of these proteins, the cold water organisms can survive below zero temperature and resist the water crystallization process which may cause the rupture in the internal cells and tissues. AFP’s have attracted attention and interest in food industries and cryopreservation. Objective: With the increase in the availability of genomic sequence data of protein, an automated and sophisticated tool for AFP recognition and identification is in dire need. The sequence and structures of AFP are highly distinct, therefore, most of the proposed methods fail to show promising results on different structures. A consolidated method is proposed to produce the competitive performance on highly distinct AFP structure. Methods: In this study, we propose to use machine learning-based algorithms Principal Component Analysis (PCA) followed by Gradient Boosting (GB) for antifreeze protein identification. To analyze the performance and validation of the proposed model, various combinations of two segments composition of amino acid and dipeptide are used. PCA, in particular, is proposed to dimension reduction and high variance retaining of data which is followed by an ensemble method named gradient boosting for modelling and classification. Results: The proposed method obtained the superfluous performance on PDB, Pfam and Uniprot dataset as compared with the RAFP-Pred method. In experiment-3, by utilizing only 150 PCA components a high accuracy of 89.63 was achieved which is superior to the 87.41 utilizing 300 significant features reported for the RAFP-Pred method. Experiment-2 is conducted using two different dataset such that non-AFP from the PISCES server and AFPs from Protein data bank. In this experiment-2, our proposed method attained high sensitivity of 79.16 which is 12.50 better than state-of-the-art the RAFP-pred method. Conclusion: AFPs have a common function with distinct structure. Therefore, the development of a single model for different sequences often fails to AFPs. A robust results have been shown by our proposed model on the diversity of training and testing dataset. The results of the proposed model outperformed compared to the previous AFPs prediction method such as RAFP-Pred. Our model consists of PCA for dimension reduction followed by gradient boosting for classification. Due to simplicity, scalability properties and high performance result our model can be easily extended for analyzing the proteomic and genomic dataset.


1998 ◽  
Vol 63 (2) ◽  
pp. 211-221 ◽  
Author(s):  
Miloš Tichý ◽  
Luděk Ridvan ◽  
Miloš Buděšínský ◽  
Jiří Závada ◽  
Jaroslav Podlaha ◽  
...  

The axially chiral bis(α-amino acid)s cis-2 and trans-2 as possible building blocks for polymeric structures of novel type of helicity were prepared. Their configuration has been determined by NMR spectroscopy and, in the case of the trans-isomer, confirmed by single-crystal X-ray diffraction. Analogous pair of stereoisomeric diacids cis-3 and trans-3, devoid of the amino groups, was also prepared and their configuration assigned. The observed differences in the NMR spectra of cis- and trans-isomers of 2 and 3 are discussed from the viewpoint of their different symmetry properties.


Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 117
Author(s):  
Thekla Cordes ◽  
Christian M. Metallo

Itaconate is a small molecule metabolite that is endogenously produced by cis-aconitate decarboxylase-1 (ACOD1) in mammalian cells and influences numerous cellular processes. The metabolic consequences of itaconate in cells are diverse and contribute to its regulatory function. Here, we have applied isotope tracing and mass spectrometry approaches to explore how itaconate impacts various metabolic pathways in cultured cells. Itaconate is a competitive and reversible inhibitor of Complex II/succinate dehydrogenase (SDH) that alters tricarboxylic acid (TCA) cycle metabolism leading to succinate accumulation. Upon activation with coenzyme A (CoA), itaconyl-CoA inhibits adenosylcobalamin-mediated methylmalonyl-CoA (MUT) activity and, thus, indirectly impacts branched-chain amino acid (BCAA) metabolism and fatty acid diversity. Itaconate, therefore, alters the balance of CoA species in mitochondria through its impacts on TCA, amino acid, vitamin B12, and CoA metabolism. Our results highlight the diverse metabolic pathways regulated by itaconate and provide a roadmap to link these metabolites to potential downstream biological functions.


2006 ◽  
pp. 4847-4849 ◽  
Author(s):  
Bulusu Jagannadh ◽  
Marepally Srinivasa Reddy ◽  
Chennamaneni Lohitha Rao ◽  
Anabathula Prabhakar ◽  
Bharatam Jagadeesh ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huanyong Li ◽  
Xiaoqian Tang ◽  
Xiuyan Yang ◽  
Huaxin Zhang

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.


Synlett ◽  
2005 ◽  
pp. 212-216 ◽  
Author(s):  
Frank Schweizer ◽  
Marlin Penner ◽  
David Taylor ◽  
Danielle Desautels ◽  
Kirk Marat

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.


2019 ◽  
Vol 58 ◽  
pp. 28-36 ◽  
Author(s):  
Hisaaki Hirose ◽  
Christos Tsiamantas ◽  
Takayuki Katoh ◽  
Hiroaki Suga

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