Elaboration of the Corticosteroid Synthesis Pathway in Primates through a Multistep Enzyme
| Autor: | Carrie F. Olson-Manning |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Primates
Metabolic network Context (language use) Computational biology Biology Evolution Molecular 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Adrenal Cortex Hormones Gene Duplication Gene duplication Genetics Animals Humans Steroid 11-beta-hydroxylase Molecular Biology Discoveries Ecology Evolution Behavior and Systematics 030304 developmental biology chemistry.chemical_classification 0303 health sciences Aldosterone Cytochrome P450 Metabolic pathway Enzyme chemistry biology.protein Steroid 11-beta-Hydroxylase 030217 neurology & neurosurgery |
| Zdroj: | Mol Biol Evol |
| ISSN: | 1537-1719 0737-4038 |
| DOI: | 10.1093/molbev/msaa080 |
| Popis: | Metabolic networks are complex cellular systems dependent on the interactions among, and regulation of, the enzymes in the network. Although there is great diversity of types of enzymes that make up metabolic networks, the models meant to understand the possible evolutionary outcomes following duplication neglect specifics about the enzyme, pathway context, and cellular constraints. To illuminate the mechanisms that shape the evolution of biochemical pathways, I functionally characterize the consequences of gene duplication of an enzyme family that performs multiple subsequent enzymatic reactions (a multistep enzyme) in the corticosteroid pathway in primates. The products of the corticosteroid pathway (aldosterone and cortisol) are steroid hormones that regulate metabolism and stress response in tetrapods. These steroid hormones are synthesized by a multistep enzyme Cytochrome P450 11B (CYP11B) that performs subsequent steps on different carbon atoms of the steroid derivatives. Through ancestral state reconstruction and in vitro characterization, I find that the primate ancestor of the CYP11B1 and CYP11B2 paralogs had moderate ability to synthesize both cortisol and aldosterone. Following duplication in Old World primates, the CYP11B1 homolog specialized on the production of cortisol, whereas its paralog, CYP11B2, maintained its ability to perform multiple subsequent steps as in the ancestral pathway. Unlike CYP11B1, CYP11B2 could not specialize on the production of aldosterone because it is constrained to perform earlier steps in the corticosteroid synthesis pathway to achieve the final product aldosterone. These results suggest that enzyme function, pathway context, along with tissue-specific regulation, both play a role in shaping potential outcomes of metabolic network elaboration. |
| Databáze: | OpenAIRE |
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