Urofuranic acids

The general structure of urofuranic acids with R = H or R = CH ₃

Urofuransäuren ( engl. Urofuran acids ) are a group of dicarboxylic acids having a furan ring include and as a metabolic product of furanoid fatty acids formed.

Occurrence and origin

The shorter-chain urofuranic acids are found in animal and human blood, as well as in urine (origin of the name).

physiology

In the case of uremia , urofuranic acids, especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid ( CMPF , in the diagram n and m = 2, R = CH ₃ ), accumulate in the blood. Due to the strong binding to human albumin , this metabolic product cannot be removed from the blood even by hemodialysis . CMPF can be removed from the blood using peritoneal dialysis . CMPF is the main inhibitor of protein-binding agents and a uremic toxin . It directly inhibits the organic anion transporter type 1 and type 2 (OAT1, OAT2), which disrupts the transport or excretion of various drugs and endogenous organic acids. Thyroxine (T ₄ ) is one of these endogenous acids . In patients with uremia, up to 0.2 m mol / l CMPF is found in the serum. The binding constant K _a of CMPF to albumin is 1.3x10 ⁷ mol ⁻¹ . It forms 1: 1 complexes, especially at binding site 1 of albumin.

discovery

The urofuranic acids were discovered in 1979 by the Austrian chemists Michael and Gerhard Spiteller at the University of Bayreuth as a metabolic product of the furan fatty acids in the urine.

further reading

• T. Nishio, N. Takamura, R. Nishii, J. Tokunaga, M. Yoshimoto, K. Kawai: Influences of haemodialysis on the binding sites of human serum albumin: possibility of an efficacious administration plan using binding inhibition. In: Nephrol. Dial. Transplant. 23, 2008, pp. 2304-2310 PMID 18390890 .
• H. Sun, Y. Huang, L. Frassetto, LZ Benet: Effects of uremic toxins on hepatic uptake and metabolism of erythromycin. In: Drug Metab Dispos 32, 2004, pp. 1239-1246, PMID 15286055 .
• Claudio Ronco, James F. Winchester: Dialysis, dialyzers, and sorbents. Karger Publishers, 2001, ISBN 3-805-57225-5 , pp. 53-60, limited preview in the Google book search
• Toshi Sassa, Hiroyuki Matsuno, Masayuki Niwa, Osamu Kozawa, Naohito Takeda, Toshimitu Niwa, Takashi Kumada, Toshihiko Uematsu: Measurement of furancarboxylic acid, a candidate for uremic toxin, in human serum, hair, and sweat, and analysis of pharmacological actions in vitro. In: Archives of Toxicology . 73, 2000, pp. 649-654, doi : 10.1007 / s002040050020 .
• Touichi Tanaka, Hideharu Ikebuchi, Jun-ichi Sawada, Yoshiko Tanaka: Production of antiserum for sensitive enzyme-linked immunosorbent assay of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid by chemiluminescence. In: Lipids. 33, 1998, pp. 733-736, doi : 10.1007 / s11745-998-0264-0 .
• K. Hannemann, V. Puchta, E. Simon, H. Ziegler, G. Ziegler, G. Spiteller: The common occurrence of furan fatty acids in plants. In: Lipids 24, 1989, pp. 296-298, PMID 2755307 .
• DM Sand, H. Schlenk, H. Thoma, G. Spiteller: Catabolism of fish furan fatty acids to urofuran acids in the rat. In: Biochim. Biophys. Acta 751, 1983, pp. 455-461, PMID 6849955 .
• Juergen Pfordt, Heinz Thoma, Gerhard Spiteller: Identification, structure derivation and synthesis of previously unknown urofuranic acids in human blood. In: Liebigs Annalen der Chemie 1981, pp. 2298-2308, doi : 10.1002 / jlac.198119811217 .

Individual evidence

1. ↑ FD Gunstone: Fatty Acid and Lipid Chemistry. Verlag Springer, 1996, p. 16, ISBN 0-834-21342-7 restricted preview in the Google book search.
2. ↑ Yasuhiro Tsutsumi, Toru Maruyama, Akira Takadate, Masafumi Goto, Hiroshi Matsunaga, Masaki Otagiri: Interaction Between Two Dicarboxylate Endogenous Substances, Bilirubin and an Uremic Toxin, 3-Carboxy-4-Methyl-5-Propyl-2-Furanpropanoic Acid, on Human Serum Albumin. In: Pharmaceutical Research . 16, pp. 916-923, doi : 10.1023 / A: 1018842506896 .
3. ^ Herbert E. Spiegel: Advances in clinical chemistry. Volume 29, Academic Press, 1992, ISBN 0-120-10329-X , pp. 74-75, limited preview in Google book search.
4. ^ Claude Jacobs: Replacement of renal function by dialysis. Verlag Springer, 1996, ISBN 0-792-33610-0 , p. 18, limited preview in the Google book search
5. ↑ R. Vanholder, R. De Smet, N. Lameire: Protein-bound uremic solutes: the forgotten toxins In: Kidney Int . Suppl. 78, 2001, pp. S266-S270 PMID 11169024 (Review).
6. ↑ Guido Michels, Uta C. Hoppe: Metabolic emergencies. In: Emergency Medicine Repetition. 2008, pp. 199-212, doi : 10.1007 / 978-3-540-33705-8_9
7. ^ H. Sun, L. Frassetto, LZ Benet: Effects of renal failure on drug transport and metabolism In: Pharmacol Ther . 109, 2006, pp. 1-11 PMID 16085315 (Review).
8. ↑ CF Lim, BF Bernard, M. de Jong, R. Docter, EP Krenning, G. Hennemann: A furan fatty acid and indoxyl sulfate are the putative inhibitors of thyroxine hepatocyte transport in uremia In: J. Clin. Endocrinol. Metab. 76, 1993, pp. 318-324 PMID 8432774 .
9. ↑ CF Lim, JR Stockigt, AJ Curtis, KN ​​Wynne, JW Barlow, DJ Topliss: A naturally occurring furan fatty acid enhances drug inhibition of thyroxine binding in serum In: Metab. Clin. Exp. 42, 1993, pp. 1468-1474 PMID 8231843 .
10. ^ Y. Tsutsumi, T. Deguchi, M. Takano, A. Takadate, WE Lindup, M. Otagiri: Renal disposition of a furan dicarboxylic acid and other uremic toxins in the rat. In: J. Pharmacol. Exp. Ther. 303, 2002, pp. 880-887, PMID 12388676 , doi : 10.1124 / jpet.303.2.880 .
11. ↑ H. Mabuchi, H. Nakahashi: A major inhibitor of phenytoin binding to serum protein in uremia. In: Nephron 48, 1988, pp. 310-314, PMID 3362278 .
12. ↑ SJ Henderson, WE Lindup: Interaction of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, an inhibitor of plasma protein binding in uremia, with human albumin. In: Biochem. Pharmacol. 40, 1990, pp. 2543-2548, PMID 2268372 .
13. ↑ T. Sakai, A. Takadate, M. Otagiri: Characterization of binding site of uremic toxins on human serum albumin. In: Biol Pharm Bull . 18, 1995, pp. 1755-1761, PMID 8787801 .
14. ↑ M. Spiteller, G. Spiteller: Separation and characterization of acidic urine components. In: J. Chromatogr. B 164, 1979, pp. 253-317, PMID 544607 .
15. ↑ Michael Spiteller, Gerhard Spiteller, Georg-Alexander Hoyer: Urofuransaeuren - a previously unknown class of metabolic products. In: Chemischeberichte 113, 1980, pp. 699-709, doi : 10.1002 / cber.19801130227 .