P-type ATPases Essay example -- Chemical Biology, Biochemistry

Describe the mechanism of P-type ATPases; select one P-type ATPase and examine how its physiological role has been investigated. The P-type ATPases are a large family of membrane enzymes, with 476 different subtypes categorised in the Swiss-Prot protein information database. The P-type or E1-E2 ATPases were first discovered and categorised by Jens Christian Skou, a Danish physician-turned-physiologist in 1957. Skou discovered the Na+/K+ ATPase, and later shared half of the 1997 Nobel Prize for Chemistry in reward for his work (Skou 1997). As mentioned above, the P-type ATPases have a broad range of interventions, for example, the use of the Digitalis toxin in the treatment of heart failure (Rang et al. 2007). There are 5 broad classes of P-type ATPase, and numerable sub-classes. Human ATP-ases are primarily grouped in classed I, II and IV, with group III consisting of bacterial enzymes, and group V largely unclassified (Stokes and Green 2003). An especially important role of an ATPase in humans is the transport of sodium and potassium ions across the cell membrane. It is this Na+/K+ ATPase that J.C Skou discovered, and worked on for most of his academic career (Skou 1997). The fundamental basis of the P-type ATPase's ability to function is its capacity to form 2 conformational states, E1 and E2. Both of these states are ion-binding, one allowing intramembrane ion binding, and the other with an extramembrane ion binding site. The Na+/K+ ATPase is an anti-porter, transporting Na+ ions out of the cell, and K+ ions into the cell, at a 3:2 ratio (Na:K), against the concentration gradient (Lehninger et al. 2000). The process of transporting ions across the membrane is a 4 step mechanism, as shown in figure 1. Firstly, 3 N... ... a Participant in the Active Transport of Sodium and Potassium in the Human Erythrocyte. Journal of Biological Chemistry 235(6), pp. 1796-1802. Rang, H. P. et al. 2007. Rang and Dale's pharmacology. 6th ed. Edinburgh: Churchill Livingstone/Elsevier, pp. xiii, 829 p. Shull, G. E. et al. 1985. Amino-acid sequence of the catalytic subunit of the (Na+ + K+)ATPase deduced from a complementary DNA. Nature 316(6030), pp. 691-695. Skou, J. C. 1997. The Nobel Prizes 1997. Stockholm: Nobel Foundation. Skou, J. C. 2004. The Identification of the Sodium Pump. Bioscience Reports 24(4), pp. 436-451. Skou, J. C. and Esmann, M. 1992. The Na,K-ATPase. Journal of Bioenergetics and Biomembranes 24(3), pp. 249-261. Stokes, D. L. and Green, N. M. 2003. STRUCTURE AND FUNCTION OF THE CALCIUM PUMP. Annual Review of Biophysics and Biomolecular Structure 32(1), pp. 445-468.