Metabolic Intermediates in Tumorigenesis and Progression.

Traditional antitumor drugs inhibit the proliferation and metastasis of tumour cells by restraining the replication and expression of DNA. These drugs are usually highly cytotoxic. They kill tumour cells while also cause damage to normal cells at the same time, especially the hematopoietic cells that divide vigorously. Patients are exposed to other serious situations such as a severe infection caused by a decrease in the number of white blood cells. Energy metabolism is an essential process for the survival of all cells, but differs greatly between normal cells and tumour cells in metabolic pathways and metabolic intermediates. Whether this difference could be used as new therapeutic target while reducing damage to normal tissues is the topic of this paper. In this paper, we introduce five major metabolic intermediates in detail, including acetyl-CoA, SAM, FAD, NAD+ and THF. Their contents and functions in tumour cells and normal cells are significantly different. And the possible regulatory mechanisms that lead to these differences are proposed carefully. It is hoped that the key enzymes in these regulatory pathways could be used as new targets for tumour therapy.

O coração irritável nos discursos médicos anglo-americanos no fim do século XIX / Irritable heart syndrome in Anglo-American medical thought at the end of the nineteenth century

Investiga o estatuto e as condições de emergência da categoria nosológica de síndrome do coração irritável presente nos discursos médicos anglo-americanos na segunda metade do século XIX. No contexto da Guerra Civil Americana, examina elementos sócio-históricos que configuraram a atenção médica sobre os sintomas de ordem cardíaca de soldados. Destacam-se os valores morais de médicos-militares frente aos sintomas de medo em combatentes, assim como as hipóteses etiológicas britânicas e norte-americanas que consolidaram o estatuto nosológico do sofrimento dos soldados com palpitações. Propõe análise da especificidade da síndrome do coração irritável frente às categorias nosológicas do medo descritas pela nosologia psiquiátrica atual.

This paper examines the characteristics and the conditions for the emergence of the nosological category known as irritable heart syndrome to be found in Anglo-American medical literature in the second half of the nineteenth century. In the context of the American Civil War, it looks at some of the socio-historical elements, which comprised the medical care given to certain cardiac symptoms shown by soldiers. It emphasizes the moral values influencing the medical attitudes of military physicians towards symptoms of fear experienced by combatants, as well as the British and American etiological theories, which contributed to the nosological characterization of the suffering of soldiers afflicted with palpitations. Finally, it offers a brief analysis of the specific nature of the medical category known as irritable heart syndrome in the light of the categories of fear described by current psychiatric nosology.

Energetic cell sensors: a key to metabolic homeostasis.

Recent breakthrough studies suggest that metabolic signals such as AMP/NAD(+) and acetyl-CoA during fasting and feeding, respectively, translate the energetic cell status into specific transcriptional metabolic programs. Notably, NAD(+) and acetyl-CoA modulate chromatin packaging and gene expression as substrates of histone deacetylases or histone acetyltransferases, respectively. These energetic sensors regulate circadian rhythms and their related physiological processes. In addition, NAD(+) indirectly activates peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) during fasting, whereas acetyl-CoA inactivates PGC-1alpha upon feeding. In this review, we focus on recent evidence supporting the concept of an energetic code by which metabolic sensors control homeostasis during fasting and feeding and discuss its relevance to the pathophysiology of type 2 diabetes.

Inhibition of protein synthesis by acetyl-coenzyme A in a cell-free system: possible involvement of protein acetylation in the regulation of translation.

Acetyl-coenzyme A (CoASAc) inhibits the rate of incorporation of amino acid into protein in a cell-free system of mouse liver. The effect is more pronounced when exogenous mRNA (tobacco mosaic virus or globin mRNA) rather than endogenous messages are used. Micromolar concentrations of the cofactor block initiation, while millimolar concentrations cause a more general inhibition of the translation process, that affects, in addition, the elongation step. Inclusion of [1-14C]acetyl-CoA in a protein synthesis reaction mixture results in a very rapid and selective labelling of a protein of 200 kd of the 'pH 5' fraction. The possible involvement of the acetylating event in the regulation of protein synthesis is discussed.