Disease, biochemical mechanism

Table 1-2. The major causes of diseases. All of the causes listed act by influencing the various biochemical mechanisms in the cell or in the body. ...

Phytochemicals have little nutritional value and do not get absorbed in the body, but they seem to turn on certain switches in the biochemical mechanisms, which signal the beneficial pathways to maintain health, and to turn off the switches which proceed to adverse biochemical pathways. Rice bran products have demonstrated significant benefits as nutritional therapies in diabetes, hyperlipidemia, cancer, fatty liver, hypercalcuria and heart disease. There is experimental and clinical evidence for the beneficial health effects of the following bioactives of rice bran ... 

The above scientific information on rice bran phytochemicals indicates that a multitude of mechanisms are operating at the cellular level to bring about specific health effects. Several health benefits of rice bran appear to be the result of the synergistic function of the many phytochemicals, antioxidants, vitamins and minerals which operates through a specific immune response. Their role in the biochemical mechanisms at the cellular level which result in major health effects is shown in Fig. 17.1. A short overview summarizing the effect of the various phytochemicals on major health issues such as cancer, immune function, cardiovascular disease, diabetes, altered liver function and gastrointestinal and colon disease will be given below. 

The changing pattern of disease, coupled with a steady increase in our understanding of physiological and biochemical mechanisms and macromolecular structure, will continue to provide new targets for drug design. 

Maple Syrup Urine Disease Figure 18-28 shows the pathway for the degradation of branched-chain amino acids and the site of the biochemical defect that causes maple syrup urine disease. The initial findings that eventually led to the discovery of the defect in this disease were presented in three papers published in the late 1950s and early 1960s. This problem traces the history of the findings from initial clinical observations to proposal of a biochemical mechanism. 

Cardiovascular diseases are known to be accompanied by activation of lipid peroxidation processes in blood. The evidence that oxidative modification of LDL may play an important causative role in atherosclerosis has been increasing rapidly over the past several years. One of the important challenges that remains in this field of research is to go beyond the risk-factor concept to a comprehensive understanding of the biochemical mechanisms responsible for initiation and progression of lesions, and in particular to identity factors essential for atheroma development that might be susceptible to therapeutic intervention. 

A fast biological screen will necessarily be only a crude approximation of the clinical situation. To get useful biological data it is still necessary to focus on the (often hypothetical) biochemical mechanism explaining the reasons for a disease. The mechanism has to be expressed in biological activities, which can be measured in HTS, e.g. receptor affinities and enzyme inhibition. 

Other mechanisms. Many other biochemical mechanisms are known or postulated to function in disease resistance in plants, e.g., silicization of cell walls, "b" or PR ("pathogenesis-related") proteins, AVF (anti-viral factors) and "phytointerferon", or superoxide anions. These mechanisms have not been investigated as extensively as the above described mechanisms, especially in cases of "induced resistance". Space does not permit their consideration in this article. 

Payne, A. S., and Gitlin, J. D. (1998). Functional expression of the Menkes disease protein reveals common biochemical mechanisms among the copper-transporting P-type ATPases./. Biol. Chem. 273, 3765-3770. 

Althot Coronins (and particularly Coronin 1C (Coronin 3)) have been implicated in disease states, much work remains to establish functional links between transcriptional regulation and phenotypic change. One important area that will require more work is the careful delineation of the Coronin 1C promoter and its immediate upstream inputs. In addition, the biochemical mechanism of Coronin 1C activity needs to be more precisely determined and the relevant binding partners necessary for this activity need to be identified. Understanding these issues may be important for revealing how diverse signaling cascades are dis-regulated in invasive/metastatic cancer. Another... 

The biochemical mechanisms that lead to osteoporosis arc not clear. There is some thought that the disease can be aggravated by a decrease in the activity of... 

Various p-lactam antibiotics such as cephalosporins and guanylureido penicillins may cause nonimmuno-logic nephrotoxic effects. The elucidation of the precise biochemical mechanisms involved in nephrotoxicity of P-lactams is of obvious importance for their rational and efficient utilization in the clinical management of infectious disease and for development of future cephalosporins. 

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