Miscellaneous Research Topics

Does intracellular acidification contribute to infertility in varicocele?

Kamyar Ghabili, Mohammadali M. Shoja, Paul S. Agutter, Ashok Agarwal. Fertility and Sterility (2008) PMID: 18692793

Abstract. We suggest that varicocele leads to male infertility by a mechanism involving underperfusion of the testis, a shortfall in glucose supply to the tissue, decreased flux through the pentose phosphate pathway, lowering of the NADPH/NADP+ ratio and the supply of glutathione to the antioxidant systems, increased levels of reactive oxygen species, peroxidation of spermatozoon membrane lipids, and the consequent generation of acidic degradation products and sequestering of spermine. Acidification of the seminal plasma impairs sperm motility and also inhibits most antioxidant enzymes, exacerbating the accumulation of reactive oxygen species and the resultant lowering of pH.

Electromagnetic fields and prostate cancer: a possible link

Kamyar Ghabili, Mohammadali M. Shoja, Paul S. Agutter. Piezoelectricity and prostate cancer: Proposed interaction between electromagnetic field and prostatic crystalloids. Cell Biology International 32 (2008) 688-691. PMID: 18299212

Abstract: There is evidence that electromagnetic fields (EMF) play some part in the pathogenesis of prostate cancer, but the pathogenic mechanism remains unknown. The normal prostate gland and both benign and malignant prostate lesions contain abundant calcium/phosphorus crystalloids with various morphologies, which seem to be heterogeneously and diffusely distributed within the gland. We hypothesize that an environmental EMF may result in simultaneous, multidirectional and diffuse compression or expansion of these crystalloids (a piezoelectric effect). This would result in a slight mechanical distortion of the prostate, potentially altering cell behavior and enhancing the expression of specific genes, particularly those involved in suppressing apoptosis. A mathematical model of the cell mechanical effect is presented, and the hypothesis is related to current clinical evidence and to potential validation by critical laboratory tests.

Dominance seen in the light of metabolic control analysis

Paul S. Agutter, The flux summation theorem and the ‘evolution of dominance’. Journal of Theoretical Biology 254 (2008) 821-825.

Abstract: The Flux Summation Theorem (FST) is a central principle of metabolic control analysis. It describes how the control of flux through any metabolic pathway of arbitrary complexity is distributed among the component reaction steps. Two issues concerning the FST are discussed in this paper. First: it has been suggested that the theorem could, in principle, be inapplicable under certain conditions, i.e. the sum of the control coefficients of all the enzymes supporting a pathway could exceed unity. Such conditions have not been found in any species so far studied, so in practice the FST is always applicable. I argue that applicability of the FST is a precondition for phenotypic robustness and therefore for survival. Second: the FST provides a basis for explaining dominance that renders Fisher’s ‘modifier genes’ hypothesis otiose. Some recent misunderstandings of metabolic control analysis have led to the claim that this explanation is flawed and therefore that Fisher’s hypothesis can and should be reinstated. Here, these suggestions are refuted.

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