Amino Acid Synthesis and Metabolism
Rothenburg S, Koch-Nolte F, Rich A andHaag F: A polymorphic dinucleotide repeat in the rat nucleolin geneforms Z-DNA and inhibits promoter activity. Proc Natl Acad Sci USA.98:8985–8990. 2001. : :
The amino acid metabolism page details the synthesis and ..
Reactive free radicals and cellular redox stress have been proposed to directly activate Ras. NO (Nitric Oxide) promotes the direct post translational modification of Ras by single S-nitrosylation at Cys118. These results in stimulation of guanine nucleotide exchange, possibly by destabilization associates with other effectors, leading to transduction of Ras mediated signals through multiple pathways. In addition to Raf, PI3K and RalGDS other Ras effectors have been proposed, including p120GAP, PKC-zeta, Rin1, AF6, and NF1 GAP (Ref.3). TCR engagement also leads to the activation of Ras via a signaling pathway involving the activation of p56 (Lck) and PKC (Protein Kinase-C). Biochemical and genetic studies have now confirmed the functional relevance of Ras effectors. The Raf protein kinase family controls the activation of the MAPK (Mitogen-Activated Protein Kinases) pathway and plays a major role in controlling proliferation and differentiation. The PI3K mediates some of the Ras-dependent actin cytoskeleton remodeling and protection against apoptosis. The third bonafide Ras effector is RalGDS, regulates multiple processes including receptor endocytosis, cytoskeletal changes, and DNA synthesis. The Ras-Raf-MEK-ERK pathway features several oncogenes and is deregulated in approximately 30% of all human cancers. It has also emerged as a prime target for antitumor therapy (Ref.4).
Previously, Orlando () performed a study aimed atinvestigating the effects of increasing concentrations of strain GG () homogenateon cell growth and proliferation in neoplasms originating fromdifferent GI tracts, such as gastric HGC-27 and colonic DLD-1cells, focusing attention in their polyamine profile andbiosynthesis. Additionally, in order to verify which bacterialfraction was involved in the anti-proliferative effects, thecytoplasm and cell wall extracts were tested separately. Both celllines proved to be sensitive to the growth inhibition by thehighest concentrations of bacterial homogenate with a significantreduction in their polyamine concentrations. Interestingly, eitherHGC-27 or DLD-1 cells were resistant to the bacterial cell wallfractions, whereas increasing cytoplasm fraction concentrationsinduced an evident anti-proliferative effect. These data suggestedthat cytoplasm extracts could be responsible for actionon proliferation of these two cell lines from gastric and colonicneoplasms. Another probiotic, () usually prescribed in a lyophilized form,demonstrated not only to act as a carrier able to release differentactive metabolic compounds such as enzymes and trophic factorsduring its intestinal transit, but also to secrete its polyaminecontent (mainly spermine and spermidine), thus directly affectinggene expression and protein synthesis ().
De Amination | Metabolic Pathway | Metabolism
Epidemiologic reports suggest that phytoestrogenscontained in soy are causally related to protection againsthormone-dependent cancers, probably by competing with estradiol forestrogen receptors () and datafrom literature provide evidence of an association between highconsumption of phytoestrogen-rich foods and a low incidence ofbreast and prostate cancer within populations of Asian countries(). There are also dataregarding these substances and colonic neoplastic transformationwith a significant reduction in CRC risk (). The evidence is important, becausedietary intake is modifiable. Therefore, identifying dietaryphytoestrogens with antitumor activity and investigating theirmechanisms of action may lead to significant advances in theprevention of human cancer. Also cell-culture studies and animalexperiments have shown that flavonoids are tumor-inhibitory for CRC(). It has been observed thatODC activity and polyamine concentrations were significantly lowerin the mammary epithelium of rats treated with soy protein than incontrols (). Previous studiesclearly demonstrated that, although the GI tract is not a classicalsex hormonal target, sex steroid hormones can affect cellproliferation and turnover, playing an important role also in theneoplastic transformation in the colon (,).This evidence suggests that estrogens as well as phytoestrogensintroduced with diet may exert a protective role against CRC alsoin humans regardless of gender ().
The response of this metabolic pathway to dietary protein ..
Probiotics are defined as ‘live microorganismswhich, when administered in adequate amounts, confer a healthbenefit on the host’ ().Together with these positive bacterial strains, other substances,mainly found in plants have been deeply investigated for theirchemopreventive and chemotherapeutic properties against humancancers. These substances include flavonoids such as genistein(found in soy), quercetin (onions), apigenin (celery, parsley),green tea (polyphenols), etc. On these bases this chapter tries toreview data on those nutritional components useful for CRCchemoprevention in relation to their potentiality in affecting thepolyamine metabolism.
one pathway may be responsible for the synthesis of a ..
The GI tract is constantly connected with theexternal environment, therefore all the possible modifications indaily diet might significantly modify the exposure to differentcarcinogenetic factors. In this framework, the identification ofthose components in diet that may display at different degree someantitumor activity as well as the understanding of their mechanismsof action, may lead to significant advances in human cancerprevention. Several diet components have been demonstrated ashaving some anti-neoplastic activity. From the early 1970s, manystudies following different designs (e.g., correlation studies,case-control, cohort studies) have hypothesized that dietary fibersmay show protective effects against diverse neoplasms, including GIneoplasms (). Their positiveaction in the GI environment has been essentially put in relationwith the bacterial strains resident in the GI lumen ().