Embden-Meyerhof glycolytic pathway and Gluconeogenesis

Glycolysis (Embden-Meyerhof-Parnas pathway) is the most common sequence of reactions for the conversion of glucose-6-P into pyruvate in all domains of life. It generates ATP, reduced equivalents, and precursor metabolites for a multitude of essential cellular processes. During growth on substrates other then hexoses, essential glycolytic intermediates are synthesized via glyconeogenesis, reversion of EMP. While Glycolysis and glyconeogenesis are well-conserved in bacteria and eukaryotes, Archaea have developed unique variants of these pathways, presented in a separate subsystem. Striking examples of unique features of glycolytic pathways in archaea include: zero or very low ATP yields; reduction of ferredoxin rather than NADH; many unusual glycolytic enzymes, including ADP-dependent glucoand phosphofructokinases, non-orthologous PGMs, FBAs, non-phosphorylating GAP dehydrogenases, etc. Notably, less variation is observed in glyconeogenic than in glycolytic enzymes. This may reflect the independent evolution of catabolic branches in bacteria and archaea diverging from originally glyconeogenic EMP pathway (refs. 2, 5) . Since studies of archaeal glycolytic pathways have started only in early 1990s, a large number of open questions (including “missing” enzymes) remains. Out of ten enzymatic steps, which constitute classical EMP seven are reversible and work in glyconeogenesis as well. However, glycolytic reactions catalyzed by 6phosphofructokinase, pyruvate kinase and some forms of glyceraldehyde 3-phosphate dehydrogenase are not reversible (shown in red in the following slides). They are bypassed during glyconeogenesis via specific glyconeogenic enzymes (shown in blue) or by utilizing alternative routes of central carbon metabolism. Multiple alternative forms of enzymes exist in various organisms for nearly every functional role in this central pathway. Each variant is cataloged independently: each column in a Subsystem spreadsheet in SEED contains members of a single protein family assigned with a specific function. Alternative forms of enzymes can be grouped into subsets of functional roles (marked with “*”) by using “ignore alternatives” tool on a SS page in SEED. Comparative analysis of complete genomes in SEED revealed endless variations in the implementation of this all too familiar pathway in different organisms; allowed to project the accumulated knowledge from well studied organisms to many others; led to identification of missing genes and other open questions. Svetlana Gerdes and Ross Overbeek Fellowship for Interpretation of Genomes