Biochemistry, endogeneous

Some aspects of the biochemistry of metabolic processes affecting nutrients appear to have significant consequences for the expected behavior of stable carbon isotopes as tracers of diet. Specifically, we have seen that the simple model of a total scrambling of carbon atoms during endogenous biosynthesis is inconsistent with the expected pathways of some nutrients, whereas other isotopic records in ancient human tissues can be adequately accounted for by this model. 

Xenobiotic A foreign compound that has no role in the normal biochemistry of a living organism. A normal endogenous compound to one species can be a xenobiotic to another species. 

Karras J.G., Maier M.A., Lu T, Watt A., Manoharan M. Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine inter-leukin-5 receptor-alpha chain. Biochemistry 2001 40 7853-7859. 

Plastaras, J. P. Dedon, P. C. Marnett, L. J. Effects of DNA structure on oxopropenylation by the endogenous mutagens malondialdehyde and base propenal. Biochemistry 2002,41, 5033-5042. 

Hillard CJ, Cambell WB. Biochemistry and pharmacology of arachidonyl-ethanolamide, a putative endogenous cannabinoid. J Lip Res 1997 38 2383-2398. 

Saghatelian A, Trauger SA, Want EJ, Hawkins EG, Siuzdak G, Cravatt BF, Assignment of Endogenous Substrates to Enzymes by Global Metabolite Profiling, Biochemistry 43 14332—14339, 2004. 

Schmid, R., and Lester, R., Implication of conjugation of endogenous compounds—Bilirubin. In Glucuronic Acid. Free and Combined. Chemistry, Biochemistry, Pharmacology, and Medicine (G. J. Dutton, ed.), pp. 493-506. Academic Press, New York, 1966. 

Yamamoto, A., Tomoo, K., Doi, M, Ohishi, H., Inoue, M., Ishida, T., Yamamoto, D., Tsuboi, S., Okamoto, H., Okada, Y. (1992). Crystal structure of papain-succinyl-Gbi-Val-Val-Ala-Ala-p-nitroaniUde complex at 1.7-A resolution noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors. Biochemistry 31,11305-11309. 

West. S.B. and Lu, A.Y. (1972) Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds and endogenous substrates. V. Competition between cytochromes P-450 and P-448 for reductase in 3,4-benzpyrene hydro-xylation. Archives of Biochemistry and Biophysics, 153, 298-303. 

The role of the immunoassay, especially the radioimmunoassay (RIA), in clinical biochemistry has been the major factor in the tremendous advances made in that field since its introduction in 1959 (11). At present the RIA is the most powerful analytical tool available for quantitative detection of molecules of diverse structure and function in biological fluids of human, animal and now plant origin. The immunoassay comprises a unique combination of sensitivity and specificity as well as precision and applicability. With this assay technique, it is now possible to detect and very accurately measure compounds at endogenous physiological concentrations which frequently are in the range of 10 M or lower. In Table II the major characteristics of the immunoassay are listed. This method is versatile, specific, can be utilized for almost an unlimited number of compounds and has a high throughput potential. 

Pinter, M., and Friedrich, P., 1988, The calcium dependent proteolytic system calpain-calpatatin in Drosophila melanogaster, Biochem J., 253, 467-473 Pinter, M., Stierandova, A., and Friedrich, P., 1992, Purification and characterization o a Ca2 activated thiol protease from drosophila melanogaster, Biochemistry, 31, 8201-8206 Pontremoli, S., Melloni, E., Michetti, M., Salamino, F., Sparatore, B., Horecker, B., 1988, An endogenous activator of the Ca2+ -dependent proteinase of human neutrophils that increases its affinity for Ca2+, Proc. Natl. Acad. Sci., USA, 85, 1740-1743... 

Torimoto N, Ishii I, Hata M, et al. Direct interaction between substrates and endogenous steroids in the active site may change the activity of cytochrome P450 3A4. Biochemistry 2003 42 15068-15077. 

DMP accounts for all important aspects of endogenous biochemistry/biology that influence substrate selection and metabolism. For example, although the lipid 2-oleoyl glycerol is an excellent FAAH substrate in vitro, other enzymes and pathways regulate this lipid in vivo and, as a result, the loss of FAAH activity is inconsequential to the in vivo levels of this metabolite [5]. 

The diseases and disorders chosen for discussion and the order of presentation parallel subject matter taught in most first-year medical biochemistry. Chapters in the first part of the book, Nucleic Acids and Protein Structure, illustrate the relationships of protein structure and function with respect to collagen (Osteogenesis Imperfecta) and hemoglobin (Sickle Cell Anemia). The chapters Fragile X Syndrome and Hereditary Spherocytosis discuss key aspects of DNA and protein structure and their respective role in chromosomal and cytoskeletal structure. The chapter cardiac troponin and myocardial infarction provides an up-to-date demonstration of the usefulness of both structural proteins and enzymes as markers of cardiovascular disease, while the chapter cx Anti trypsin Deficiency discusses the important role of endogenous enzyme inhibitors. 

Saghatelian, A., Trauger, S.A., Want, EJ. et al. (2004) Assignment of endogenous substrates to enzymes by global metabolite profiling. Biochemistry, 43, 14332-9. 

Scheme 2 Proposed mechanism for bicarbonate-mediated peroxidation in SOD. After Cu(II) reduction (i), bicarbonate binds to the anion-binding site (ii). In (iii), HOO" reacts with bicarbonate to form peroxycarbonate (iv). In (v), the oxygen radical species formed [O ] may oxidize endogenous or exogenous substrates. This leaves bicarbonate bound to the anion-binding site (vi). (Ref 17. Reproduced by permission of American Society for Biochemistry Molecular Biology)...

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