Microbial growth in alkaline conditions presents several complications to normal biochemical activity and reproduction, as high pH is detrimental to normal cellular processes. For example, alkalinity can lead to
denaturation of DNA, instability of the
plasma membrane and inactivation of cytosolic
enzymes, as well as other unfavorable physiological changes. Thus, to adequately circumvent these obstacles, alkaliphiles must either possess specific cellular machinery that works best in the alkaline range, or they must have methods of acidifying the cytosol in relation to the extracellular environment. To determine which of the above possibilities an alkaliphile uses, experimentation has demonstrated that alkaliphilic enzymes possess relatively normal pH optimums. The determination that these enzymes function most efficiently near physiologically neutral pH ranges (about 7.5–8.5) was one of the primary steps in elucidating how alkaliphiles survive intensely basic environments. Since the cytosolic pH must remain nearly neutral, alkaliphiles must have one or more mechanisms of acidifying the
cytosol when in the presence of a highly alkaline environment. ==Mechanisms of cytosolic acidification==