Why so many proteolytic enzymes?

When studying the evolution timeline that led to modern biochemistry, one can always turn to studying protein architecture. Proteins have been called “molecular fossils” that serve to mark milestones in the “history of life” (1). There is a wide diversity of proteolytic enzymes in humans and the network of enzymes have a grand complexity that calls for investigation of how they were shaped over time (2).

In digestion there is a variety of proteolytic enzymes—pepsins, enteropeptidases, carboxypeptidases, and aminopeptidases (3). Each work to hydrolyse proteins by cleaving off amino acids from differing peptide bonds, in different stages and conditions (gastric, pancreatic and intestinal phases) and at varied pH ranges (3). The system is indeed complex, not exactly perfect (a better system may have used only a one or two enzymes), but it works and that’s evolution.

Each highly structured enzyme would have evolved accordingly at some time, and some, which may have had major roles in the past, have only minor ones now. An example of biochemical “fossils” studied currently in Germany are particular aspartic proteases (4). They are structurally similar to other proteases suggesting a common “major role” ancestor”, but have evolved now only to act in “chaperone-like” fashion for substrate binding in digestion (4).

More than 2 percent of human genes are proteases or protease inhibitors (5). New genomic data is expected reveal more about how proteases, their substrates, proteolytic complexes, inhibitors, and interactions all co-evolved (5;6). The complete human degradome—set of protease genes—is also being compared with degradomes of other mammals such as chimpanzees and mice and serving to provide further understanding of ancestral relationship of species (5;7).

Reference List

1. Caetano-Anolles G, Wang M, Caetano-Anolles D, Mittenthal JE. The origin, evolution and structure of the protein world. Biochem J 2009;417:621-37.
2. Page MJ, Di CE. Evolution of peptidase diversity. J Biol Chem 2008;283:30010-4.
3. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
4. Hulko M, Lupas AN, Martin J. Inherent chaperone-like activity of aspartic proteases reveals a distant evolutionary relation to double-psi barrel domains of AAA-ATPases. Protein Sci 2007;16:644-53.
5. Puente XS, Sanchez LM, Gutierrez-Fernandez A, Velasco G, Lopez-Otin C. A genomic view of the complexity of mammalian proteolytic systems. Biochem Soc Trans 2005;33:331-4.
6. Southan C. Exploiting new genome data and Internet resources for the phylogenetic analysis of proteases, substrates and inhibitors. Biochem Soc Trans 2007;35:599-603.
7. Ordonez GR, Puente XS, Quesada V, Lopez-Otin C. Proteolytic systems: constructing degradomes. Methods Mol Biol 2009;539:33-47.

Published by David Despain, MS, CFS

David is a science and health writer living on Long Island, New York. He's written for a variety of publications including Scientific American, Outside Online, the American Society for Nutrition's (ASN) Nutrition Notes Daily, and Institute of Food Technologists' (IFT) Food Technology magazine and Live! blog. He's also covered new findings reported at scientific meetings including Experimental Biology, AAAS, AOCS, CASW, Sigma Xi, IFT, and others on his personal blog "Evolving Health." David is also an active member of organizations including the National Association of Science Writers (NASW), the American Association for the Advancement of Science (AAAS), the American Society for Nutrition, the Institute of Food Technologists, and the National Audubon Society. David has a master's degree in human nutrition from the University of Bridgeport, and a bachelor's degree in English from University of Illinois at Springfield. He also earned his Certified Food Scientist credential from the Institute of Food Technologists.

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