Differently, according to the down-regulated pattern, there is a clear shift towards the amino acid anabolism. Therefore, the synthesis of histidine is down-regulated with three entries such as hisI, hisD and histidinol-phosphate aminotransferase (MAP4211).
Among down-regulated entries are also those required for the synthesis of methionine with four repressed genes such as metC, metH, homocysteine methyltransferase (MAP2279) and lastly cystathione beta-lyase (MAP2055). The synthesis of threonine seems down-regulated (thrC) together with the synthesis of glutamine (glnA2) and lysine with dihydrodipicolinate reductase protein (MAP2013c, MAP3619). The metabolism of carbohydrates shows during THP-1 infection an up-regulation check details of lpqI which participates
in the hydrolysis of beta-linkages in polysaccharides and the consequently release of free glucose. The down-regulated profile shows rather the Selleckchem Quisinostat opposite AG-881 datasheet process to the degradation of polysaccharides, although with formation of alpha-linkages, with glgC involved in the synthesis of glycogen. The lipid metabolism is characterized by a slight up-regulation of the synthesis of fatty acids with fabG2 and MaoC domain protein dehydratase (MAP3479c). On the other hand during the THP-1 infection, MAP’s degradation of lipids is heavily down-regulated with the repression of fadD13, fadE6 and acyl-CoA dehydrogenase (MAP3238), as well as three entries for enoyl-CoA hydratase (echA9, echA19, echA16) and fadA6. Lastly, a gene involved in the degradation of sterols, steroid delta-5-3-ketosteroid isomerase (MAP1773c), is down-regulated. Intramacrophage environment brings MAP to employ mechanisms for energy production and cofactors biosynthesis through anaerobic
pathways As far as the metabolism of cofactors and vitamins is concerned, among up-regulated genes are those specific for the synthesis of folate such as aminodeoxychorismate lyase protein (MAP1079) and dfrA along with genes responsible for the IKBKE synthesis of porphyrins (hemE, hemZ) for heme production. In addition, there is an increase in the synthesis of B12 cofactor through anaerobic process (cobT) together with the up-regulation of the synthesis of biotin (bioF) and the biosynthesis of menaquinone (menB). In opposite to the up-regulation profile, the synthesis of B12 cofactor under aerobic conditions is down-regulated with cobN required for the aerobic synthesis of its corrin ring, along with the the synthesis of coenzyme A with coaA and dephospho-CoA kinase (MAP1326). During THP-1 infection MAP up-regulates acn that is used both in tricarboxylic acid (TCA) cycle and in glyoxylate pathway. In addition there is also an up-regulation of the pentose phosphate pathway with glucose-6-phosphate 1-dehydrogenase (MAP1687).
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