A Model for the Spatial Location of Pyruvate Dehydrogenase Phosphatase in Mammalian Pyruvate Dehydrogenase Complex

G. L. Ermakov^* and B. N. Goldstein

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142292 Russia; fax: (0967) 79-0553; E-mail: ermakov@venus.iteb.serpukhov.su

^* To whom correspondence should be addressed.

Received March 18, 1998; Revision received November 10, 1998

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Recent experimental findings on the structural--functional features of pyruvate dehydrogenase phosphatase (PDP) isolated from various sources are compared. Two alternative mechanisms (a and b) of dephosphorylation of the E1 component in the pyruvate dehydrogenase complex (PDC) are discussed: a) the reaction occurs as a result of stochastic collisions of PDP and PDC, and the generation of an enzyme--substrate complex (PDP--E1--PDC) and dephosphorylation of the E1 component occur independently at different PDP binding sites on the PDC core; b) the dephosphorylation is performed simultaneously by a certain number of PDP molecules symmetrically bound on the PDC core. The second mechanism is suggested by the self-assembly theory of multicomponent enzyme systems and can be proved by kinetic experiments. Based on self-assembly principles and data on feasible binding sites of peripheral components of the PDC, the stoichiometry and mutual location of PDP, pyruvate dehydrogenase kinase, and the E1 component on the core of mammalian PDC are postulated to provide optimal functioning of the PDC. Structural mechanisms of stimulation of PDP activity by Ca²⁺ and polyamines are also discussed.

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KEY WORDS: pyruvate dehydrogenase phosphatase, pyruvate dehydrogenase complex, structural organization

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