Metabolic role and regulation of ?-alanine dehydrogenase in Rhodopseudomonas capsulata

The mevalonate pathway (also known as the cholesterol biosynthesis pathway) plays a crucial metabolic role in normal cell function as well as in the pathological environment. It leads to the synthesis of sterol and non-sterol isoprenoid biomolecules which subserve a variety of cellular functions. It is known to be deregulated in many disease processes. Statins and bisphosphonates are prominent inhibitors of the mevalonate pathway. They inhibit cell proliferation and activate apoptotic signalling and suppress tumour growth. Statins subdue metastatic spread of tumours by virtue of their ability to suppress invasion and angiogenesis. The induction of autophagy is another feature of statin effects that could contribute to the suppression of metastasis. Herein highlighted are the major signalling systems that statins engage to generate these biological effects. Statins can constrain tumour growth by influencing the expression and function of growth factor and receptor systems. They may suppress epithelial mesenchymal transition with resultant inhibition of cell survival signalling, together with the inhibition of cancer stem cell generation, and their maintenance and expansion. They can suppress ER (oestrogen receptor)-α in breast cancer cells. Statins have been implicated in the activation of the serine/threonine protein kinase AMPK (5' adenosine monophosphate-activated protein) leading to the suppression of cell proliferation. Both statins and bisphosphonates can suppress angiogenic signalling by HIF (hypoxia- inducible factor)-1/eNOS (endothelial nitric oxide synthase) and VEGF (vascular endothelial growth factor)/VEGFR (VEGF receptor). Statins have been linked with improvements in disease prognosis. Also attributed to them is the ability of cancer prevention and reduction of risk of some forms of cancer. The wide spectrum of cancer associated events which these mevalonate inhibitors appear to influence would suggest a conceivable role for them in cancer management. However, much deliberation is warranted in the design and planning of clinical trials, their scope and definition of endpoints, modes risk assessment and the accrual of benefits.

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Fer and FerT Govern Mitochondrial Susceptibility to Metformin and Hypoxic Stress in Colon and Lung Carcinoma Cells

Cells ◽

10.3390/cells10010097 ◽

2021 ◽

Vol 10 (1) ◽

pp. 97

Author(s):

Odeya Marciano ◽

Linoy Mehazri ◽

Sally Shpungin ◽

Alexander Varvak ◽

Eldad Zacksenhaus ◽

...

Keyword(s):

Cancer Cells ◽

Aerobic Glycolysis ◽

Metastatic Cancer ◽

Carcinoma Cells ◽

Metabolic Adaptation ◽

Hypoxic Stress ◽

Lung Carcinoma Cells ◽

Metabolic Role ◽

Highly Sensitive ◽

Anticancer Treatment

Aerobic glycolysis is an important metabolic adaptation of cancer cells. However, there is growing evidence that reprogrammed mitochondria also play an important metabolic role in metastatic dissemination. Two constituents of the reprogrammed mitochondria of cancer cells are the intracellular tyrosine kinase Fer and its cancer- and sperm-specific variant, FerT. Here, we show that Fer and FerT control mitochondrial susceptibility to therapeutic and hypoxic stress in metastatic colon (SW620) and non-small cell lung cancer (NSCLC-H1299) cells. Fer- and FerT-deficient SW620 and H1299 cells (SW∆Fer/FerT and H∆Fer/FerT cells, respectively) become highly sensitive to metformin treatment and to hypoxia under glucose-restrictive conditions. Metformin impaired mitochondrial functioning that was accompanied by ATP deficiency and robust death in SW∆Fer/FerT and H∆Fer/FerT cells compared to the parental SW620 and H1299 cells. Notably, selective knockout of the fer gene without affecting FerT expression reduced sensitivity to metformin and hypoxia seen in SW∆Fer/FerT cells. Thus, Fer and FerT modulate the mitochondrial susceptibility of metastatic cancer cells to hypoxia and metformin. Targeting Fer/FerT may therefore provide a novel anticancer treatment by efficient, selective, and more versatile disruption of mitochondrial function in malignant cells.

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Unraveling the Metabolic Potential of Asgardarchaeota in a Sediment from the Mediterranean Hydrocarbon-Contaminated Water Basin Mar Piccolo (Taranto, Italy)

Microorganisms ◽

10.3390/microorganisms9040859 ◽

2021 ◽

Vol 9 (4) ◽

pp. 859

Author(s):

Andrea Firrincieli ◽

Andrea Negroni ◽

Giulio Zanaroli ◽

Martina Cappelletti

Keyword(s):

Archaeal Community ◽

Hydrocarbon Biodegradation ◽

Natural Ecosystems ◽

Central Mediterranean ◽

Metabolic Potential ◽

Metabolic Role ◽

Sequencing Studies ◽

Terrestrial Environments ◽

Metagenome Sequencing ◽

Aliphatic And Aromatic Hydrocarbons

Increasing number of metagenome sequencing studies have proposed a central metabolic role of still understudied Archaeal members in natural and artificial ecosystems. However, their role in hydrocarbon cycling, particularly in the anaerobic biodegradation of aliphatic and aromatic hydrocarbons, is still mostly unknown in both marine and terrestrial environments. In this work, we focused our study on the metagenomic characterization of the archaeal community inhabiting the Mar Piccolo (Taranto, Italy, central Mediterranean) sediments heavily contaminated by petroleum hydrocarbons and polychlorinated biphenyls (PCB). Among metagenomic bins reconstructed from Mar Piccolo microbial community, we have identified members of the Asgardarchaeota superphylum that has been recently proposed to play a central role in hydrocarbon cycling in natural ecosystems under anoxic conditions. In particular, we found members affiliated with Thorarchaeota, Heimdallarchaeota, and Lokiarchaeota phyla and analyzed their genomic potential involved in central metabolism and hydrocarbon biodegradation. Metabolic prediction based on metagenomic analysis identified the malonyl-CoA and benzoyl-CoA routes as the pathways involved in aliphatic and aromatic biodegradation in these Asgardarchaeota members. This is the first study to give insight into the archaeal community functionality and connection to hydrocarbon degradation in marine sediment historically contaminated by hydrocarbons.

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Efficient Amino Donor Recycling in Amination Reactions: Development of a New Alanine Dehydrogenase in Continuous Flow and Dialysis Membrane Reactors

Catalysts ◽

10.3390/catal11040520 ◽

2021 ◽

Vol 11 (4) ◽

pp. 520

Author(s):

David Roura Padrosa ◽

Zoya Nisar ◽

Francesca Paradisi

Keyword(s):

Continuous Flow ◽

Membrane Reactors ◽

Dialysis Membrane ◽

Widespread Application ◽

Recycling System ◽

Alanine Dehydrogenase ◽

Halomonas Elongata ◽

Amino Donor ◽

Recycling Systems ◽

Excellent Stability

Transaminases have arisen as one of the main biocatalysts for amine production but despite their many advantages, their stability is still a concern for widespread application. One of the reasons for their instability is the need to use an excess of the amino donor when trying to synthesise amines with unfavourable equilibria. To circumvent this, recycling systems for the amino donor, such as amino acid dehydrogenases or aldolases, have proved useful to push the equilibria while avoiding high amino donor concentrations. In this work, we report the use of a new alanine dehydrogenase from the halotolerant bacteria Halomonas elongata which exhibits excellent stability to different cosolvents, combined with the well characterised CbFDH as a recycling system of L-alanine for the amination of three model substrates with unfavourable equilibria. In a step forward, the amino donor recycling system has been co-immobilised and used in flow with success as well as re-used as a dialysis enclosed system for the amination of an aromatic aldehyde.

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