Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

01 January 2008

Use of di- and tripropionate substrate analogs to probe the active site of human recombinant coproporphyrinogen oxidase

Justin B. MorgenthalerABDE, Reyna L. BartoAB, Timothy D. LashADEF, Marjorie A. JonesADEFG

Med Sci Monit 2008; 14(1): BR1-7 :: ID: 636046

Abstract

Background
Defects in the enzyme coproporphyrinogen oxidase result in accumulation of porphyrins which may affect the severity of a subset of porphyrias. Thus evaluation of this enzyme for substrate selectivity is of value. Kinetic evaluations of recombinant human coproporphyrinogen oxidase have been undertaken using six di- and tripropionate analogs of the natural substrate coproporphyrinogen-III. These substrate analogs were modified by having alkyl groups in place of one or both of the ring 13- or 17-propionate moieties.
Material and Method
Cloned human enzyme was incubated with analogs under apparent first order conditions and with various substrate concentrations. The kinetic values, K(m) and V(max), were determined.
Results
Relative to the authentic substrate, the K(m) values for the 13-ethyl, dimethyl and diethyl porphyrinogens were very comparable whereas the K(m) values were much higher using dipropyl and dibutyl porphyrinogen and much lower for the 17-ethyl analog. For the dipropionate analogs, the V(max) values were an apparent function of the carbon length of the substituent on the C and D rings, with longer carbon length severely reducing product formation by some 4-5 orders of magnitude. Also, the two isomeric tripropionates that were tested indicated that it was more detrimental to have an ethyl group at the 13-position for both binding and catalysis.
Conclusions
This work extends our understanding of porphyrin ring substituent effects reported by Cooper et al. (2005). The substituents on both the C and D rings have significant effects on both the substrate binding and catalysis by this important enzyme.

Keywords: Recombinant Proteins - metabolism, Propionates - metabolism, Porphyrins - metabolism, Molecular Structure, Kinetics, Substrate Specificity, Coproporphyrinogen Oxidase - metabolism, Catalytic Domain

Add Comment 0 Comments

704 2

Editorial

01 December 2023 : Editorial  

Editorial: Outbreaks of Post-Pandemic Childhood Pneumonia and the Re-Emergence of Endemic Respiratory Infections

Dinah V. Parums

DOI: 10.12659/MSM.943312

Med Sci Monit 2023; 29:e943312

0:00

In Press

08 Dec 2023 : Clinical Research  

Association Between Influenza Vaccine Uptake and Health Awareness: A Cross-Sectional Questionnaire-Based St...

Med Sci Monit In Press; DOI:  

04 Dec 2023 : Animal Research  

Effects of Intrathecal Ketamine on Cerebrospinal Fluid Levels of Brain-Derived Neurotrophic Factor and Mech...

Med Sci Monit In Press; DOI:  

01 Dec 2023 : Clinical Research  

Risk Factors and Clinical Outcomes of COVID-19 Infection in Multiple Sclerosis Patients: A Retrospective St...

Med Sci Monit In Press; DOI:  

30 Nov 2023 : Review article  

Decoding the Neurological Sequelae of General Anesthesia: A Review

Med Sci Monit In Press; DOI:  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

0:00

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750