The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology. Very recently, a series of new discoveries have been made that are bound to have distinguished implications for bioenergetics, physiology, human pathology, and clinical diagnosis and that suggest that deregulation of the creatine kinase (CK) system is associated with a variety of diseases. Disturbances of the CK system have been observed in muscle, brain, cardiac, and renal diseases as well as in cancer. On the other hand, Cr and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and antidiabetic effects and to protect tissues from hypoxic, ischemic, neurodegenerative, or muscle damage. Oral Cr ingestion is used in sports as an ergogenic aid, and some data suggest that Cr and creatinine may be precursors of food mutagens and uremic toxins. These findings are discussed in depth, the interrelationships are outlined, and all is put into a broader context to provide a more detailed understanding of the biological functions of Cr and of the CK system.

like the PK-ATP-CK system described above (Dillon & Clark, 1990), play a fundamental role in metabolic regulation (Srivastava & Bernhard, 1986, 1987).

Yarrowia lipolytica has been developed as a production host for a large variety of biotechnological applications. Efficacy and safety studies have demonstrated the safe use of Yarrowia-derived products containing significant proportions of Yarrowia biomass (as for DuPont's eicosapentaenoic acid-rich oil) or with the yeast itself as the final product (as for British Petroleum's single-cell protein product). The natural occurrence of the species in food, particularly cheese, other dairy products and meat, is a further argument supporting its safety. The species causes rare opportunistic infections in severely immunocompromised or otherwise seriously ill people with other underlying diseases or conditions. The infections can be treated effectively by the use of regular antifungal drugs, and in some cases even disappeared spontaneously. Based on our assessment, we conclude that Y. lipolytica is a ''safe-to-use'' organism.

Bacillus subtilis is both a model organism for basic research and an industrial workhorse, yet there are major gaps in our understanding of the genomic heritage and provenance of many widely used strains. We analyzed 17 legacy strains dating to the early years of B. subtilis genetics. For three-NCIB 3610 T , PY79, and SMY-we performed comparative genome sequencing. For the remainder, we used conventional sequencing to sample genomic regions expected to show sequence heterogeneity. Sequence comparisons showed that 168, its siblings (122, 160, and 166), and the type strains NCIB 3610 and ATCC 6051 are highly similar and are likely descendants of the original Marburg strain, although the 168 lineage shows genetic evidence of early domestication. Strains 23, W23, and W23SR are identical in sequence to each other but only 94.6% identical to the Marburg group in the sequenced regions. Strain 23, the probable W23 parent, likely arose from a contaminant in the mutagenesis experiments that produced 168. The remaining strains are all genomic hybrids, showing one or more "W23 islands" in a 168 genomic backbone. Each traces its origin to transformations of 168 derivatives with DNA from 23 or W23. The common prototrophic lab strain PY79 possesses substantial W23 islands at its trp and sac loci, along with large deletions that have reduced its genome 4.3%. SMY, reputed to be the parent of 168, is actually a 168-W23 hybrid that likely shares a recent ancestor with PY79. These data provide greater insight into the genomic history of these B. subtilis legacy strains.