Regulatory Properties of Three Human Pyruvate Kinases

Rh, Bigley; Rd, Koler; Richterich, R.

doi:10.1159/000459340

Enzyme

1974

DOI: 10.1159/000459340

|View full text |Cite

Regulatory Properties of Three Human Pyruvate Kinases

Bigley Rh¹,

Koler Rd²,

R. Richterich³

Abstract: The activities of three human pyruvate kinases are affected to different degrees by P-enolpyruvate, fructose-1,6-diphosphate, ATP, and alanine. PK I and PK II are found in liver, kidney, and erythrocytes. Modulation of these activities may promote glycolysis, or impede glycolysis to allow for efficient gluconeogenesis. PK III, found in all human tissues tested except erythrocytes, can support active glycolysis at all times, regardless of the levels of the ligands studied.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1976

2009

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

(1 citation statement)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The enzyme has been extensively reviewed by Kayne . Mammalian PK exists in four isoforms with characteristics tuned to specific metabolic requirements of different tissues , . All of the isoforms, except the muscle isoform, exhibit typical allosteric behavior.…”

mentioning

confidence: 99%

Functional Energetic Landscape in the Allosteric Regulation of Muscle Pyruvate Kinase. 3. Mechanism

Heřman

Lee

2009

Biochemistry

View full text Add to dashboard Cite

Mammalian pyruvate kinase exists in four isoforms with characteristics tuned to specific metabolic requirements of different tissues. All of the isoforms, except the muscle isoform, exhibit typical allosteric behavior. The case of the muscle isoform is a conundrum. It is inhibited by an allosteric inhibitor, Phe, yet it has traditionally not been considered as an allosteric enzyme. In this series of study, an energetic landscape of rabbit muscle pyruvate kinase (RMPK) was established. The phenomenon of inhibition by Phe is shown to be physiological. Furthermore, the thermodynamics for the temperature fluctuation and concomitant pH change as a consequence of muscle activity were elucidated. We have shown that: 1. The differential number of protons released or absorbed with regards to the various linked reactions adds another level of control to shift the binding constants and equilibrium of active⇆inactive state changes; the latter controls quantitatively the activity of RMPK. 2. ADP plays a major role in the allosteric mechanism in RMPK under physiological temperatures. Depending on the temperature, ADP can assume duel and opposite roles of being an inhibitor by binding preferentially to the inactive form and a substrate. 3. Simulation of the RMPK behavior under physiological conditions shows that the net results of the twenty one thermodynamic parameters involved in the regulation are well tuned to allow maximal response of the enzyme to even minute changes of temperature and ligand concentrations. KeywordsTwo state model; allosterism; thermodynamic parameters; binding constants; predictions Pyruvate kinase, an important glycolytic enzyme, catalyzes a transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP. This process yields a molecule of pyruvate and ATP. The enzyme has been extensively reviewed by Kayne (1). Mammalian PK exists in four isoforms with characteristics tuned to specific metabolic requirements of different tissues (2, 3). All of the isoforms, except the muscle isoform, exhibit typical allosteric behavior. The case of the muscle isoform is a conundrum. It is inhibited by an allosteric inhibitor, Phe, yet it has traditionally not been considered as an allosteric enzyme because the concentration required to elicit demonstrable inhibitory effect is too high to be considered physiological. In this series of study the goal is to establish an energetic landscape of rabbit muscle pyruvate kinase (RMPK) in order to resolve this issue of whether the phenomenon of inhibition by Phe is physiological. Furthermore, there is a long standing interest in the temperature fluctuation and

show abstract

mentioning

confidence: 99%

Functional Energetic Landscape in the Allosteric Regulation of Muscle Pyruvate Kinase. 3. Mechanism

Heřman

Lee

2009

Biochemistry

View full text Add to dashboard Cite

show abstract

Influence of glucose and inhibitors of glycolysis on release of total proteins and enzymes from human leukocytes

Lahrichi

Tarallo

Houpert

et al. 1977

Clinica Chimica Acta

View full text Add to dashboard Cite

Hysteretic response of human erythrocyte pyruvate kinase to phosphoenolpyruvate. Potential role in regulation of 2,3-bisphosphoglycerate metabolism.

Badwey¹,

Westhead²

1976

Journal of Biological Chemistry

View full text Add to dashboard Cite

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Regulatory Properties of Three Human Pyruvate Kinases

Cited by 3 publications

References 15 publications

Functional Energetic Landscape in the Allosteric Regulation of Muscle Pyruvate Kinase. 3. Mechanism

Functional Energetic Landscape in the Allosteric Regulation of Muscle Pyruvate Kinase. 3. Mechanism

Influence of glucose and inhibitors of glycolysis on release of total proteins and enzymes from human leukocytes

Hysteretic response of human erythrocyte pyruvate kinase to phosphoenolpyruvate. Potential role in regulation of 2,3-bisphosphoglycerate metabolism.

Contact Info

Product

Resources

About