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What is the Oxyrase® Enzyme System? | Oxyrase Inc.

What is the Oxyrase® Enzyme System?

A biological oxygen scavenger utilizing bacterial respiratory enzyme complexes

0.1μm
Membrane fragment size
4e⁻
Electrons per O₂ molecule
6.8-9.4
Active pH range
H₂O
Only byproduct

Bacterial Membrane Fragments with Intact Respiratory Enzymes

The Oxyrase® Enzyme System consists of sterile cytoplasmic membrane fragments (~0.1 micron) derived from Escherichia coli. These fragments retain functional electron transport chain (ETC) components that catalyze the four-electron reduction of molecular oxygen directly to water.

1

Membrane Fragments

E. coli cytoplasmic membrane with intact ETC1

2

Electron Transfer

Dehydrogenases → cytochromes → O₂2

3

Water Formation

O₂ + 4H⁺ + 4e⁻ → 2H₂O3

Two-Stage Electron Transfer Mechanism

Stage 1: Substrate Dehydrogenation

FAD-dependent dehydrogenases oxidize organic substrates:

Lactate → Pyruvate
Succinate → Fumarate
Formate → CO₂

Electrons transferred to FAD → FADH₂

Stage 2: Terminal Oxidation

Electrons flow through:

Iron-sulfur clusters
Cytochrome proteins
Cytochrome c oxidase (Complex IV)

Final reduction: 4e⁻ + 4H⁺ + O₂ → 2H₂O

Complete Electron Transport Pathway

Substrate-H₂ → Dehydrogenase → FAD → Fe-S clusters → Quinones → Cytochrome b → Cytochrome c → Cytochrome oxidase → O₂ → H₂O

Enzyme Activity and Kinetics

Oxygen Reduction Rate by Temperature

40°C (Optimal)
100% Activity
37°C (Physiological)
95% Activity
25°C (Room Temp)
60% Activity
5°C (Refrigeration)
20% Activity

Activity Definition

1 Oxyrase Unit = The amount of enzyme that reduces dissolved oxygen at a rate of 1% per second under standard conditions (37°C, pH 8.4)

Standard concentration: 30 Units/mL
Time to ppb O₂ levels: ~4 minutes (with 0.3 Units in solution)

Enzyme System Characteristics

S

Substrate Requirements

Requires organic electron donors: lactate (10-20 mM), succinate, formate, or α-glycerophosphate.4 Substrate-specific dehydrogenases catalyze initial oxidation step.

C

Cofactors

FAD-dependent dehydrogenases. Heme groups in cytochrome proteins. Iron-sulfur clusters for electron transfer.5 No external cofactor addition required.

pH

pH Sensitivity

Active range: pH 6.8-9.4. Optimal activity at pH 8.0.6 Lower pH values require increased enzyme concentration or extended reaction time.

T

Temperature Range

Functions from 5-60°C. Maximum activity at 30-40°C.7 Maintains activity at 40°C for extended periods. Reduced activity at refrigeration temperatures.

R

Continuous Activity

Unlike chemical reducing agents, enzymatic catalysis continues as long as substrate and oxygen are present.8 Self-regenerating reduction system.

P

Reaction Products

Terminal reduction produces only water (H₂O). Substrate oxidation yields pyruvate, fumarate, or CO₂ depending on electron donor used.9

Enzymatic vs. Chemical Oxygen Removal Mechanisms

Characteristic Enzymatic (Oxyrase®) Thioglycolate L-Cysteine Sodium Sulfide
Reduction Mechanism Enzymatic catalysis via electron transport chain Chemical reduction via -SH groups Chemical reduction via -SH groups Chemical reduction via S²⁻ oxidation
Stoichiometry 4e⁻ + 4H⁺ + O₂ → 2H₂O 2 RSH + O₂ → RSSR + H₂O 2 RSH + O₂ → RSSR + H₂O 2 S²⁻ + O₂ → 2 S⁰ + 2 O²⁻
Catalytic Nature True catalyst (regenerates) Stoichiometric reagent Stoichiometric reagent Stoichiometric reagent
Reaction Products H₂O only Disulfide (RSSR) Cystine (disulfide) Elemental sulfur, H₂S
Continuous Scavenging Yes (with substrate) Depletes over time Depletes over time Depletes over time
pH Dependence 6.8-9.4 (enzyme stability) Higher pH increases rate pH 7.0-8.5 optimal Very pH dependent
Temperature Dependence Enzyme kinetics (Q₁₀ ~2) Chemical kinetics Chemical kinetics Chemical kinetics
Specificity High (only reduces O₂) Moderate (reduces other oxidants) Moderate (reduces other oxidants) Low (very non-specific)

Key Scientific Distinction

Oxyrase® is a true enzymatic catalyst that regenerates with substrate addition, whereas chemical reducing agents are consumed stoichiometrically.10,15 The enzymatic mechanism achieves complete four-electron reduction of O₂ to H₂O without accumulation of reactive oxygen intermediates (O₂⁻, H₂O₂, OH·).12

Molecular Components of the Enzyme System

Dehydrogenases

  • Lactate dehydrogenase – Oxidizes lactate to pyruvate
  • Succinate dehydrogenase – Part of Complex II
  • Formate dehydrogenase – Oxidizes formate to CO₂
  • FAD cofactors – Electron acceptors

Electron Carriers

  • Iron-sulfur clusters – [2Fe-2S], [4Fe-4S]
  • Quinones – Ubiquinone (CoQ)
  • Cytochrome b – Heme proteins
  • Cytochrome c – Mobile carrier

Terminal Oxidase

  • Cytochrome c oxidase – Complex IV
  • Heme a/a₃ centers – Catalytic sites
  • Copper centers (CuA, CuB) – Electron transfer
  • O₂ binding site – 4-electron reduction

Membrane Fragment Structure

The cytoplasmic membrane fragments are approximately 0.1 microns in diameter, containing intact phospholipid bilayers with embedded protein complexes.1 The orientation preserves the natural topology of the respiratory chain, with substrate-binding sites exposed to the external medium and oxygen reduction occurring at the membrane interior.

Technical Specifications

Parameter Specification Notes
Enzyme Activity Minimum 30 Units/mL 1 Unit = 1%/sec O₂ reduction at 37°C, pH 8.416
Particle Size ~0.1 micron Membrane vesicles/fragments1
Source Organism Escherichia coli Cytoplasmic membrane preparation1
pH Optimum 8.0 Active range: 6.8-9.46
Temperature Optimum 30-40°C Active range: 5-60°C7
Substrate Requirement 10-20 mM Lactate, succinate, formate, or α-glycerophosphate4
Oxygen Reduction Time 4 minutes to ppb levels With 0.3 Units at 37°C16
Reaction Stoichiometry O₂ + 4e⁻ + 4H⁺ → 2H₂O Complete 4-electron reduction3
Cofactors FAD, heme, Fe-S clusters Intrinsic to enzyme system5
Km for O₂ Low micromolar range High affinity for oxygen11
Storage Stability ≤-20°C Freeze-thaw tolerant17
Appearance Slightly turbid solution Due to membrane fragment suspension1

Temperature-Concentration Relationship

30-50°C: 3% enzyme concentration18
25°C: >6% enzyme concentration18
20°C: >9% enzyme concentration18
5-10°C: Significantly reduced activity7

pH Effects

pH 8.0: Optimal activity6
pH 7.0-7.5: Good activity6
pH 6.8-6.9: Reduced activity6
pH <6.8 or >9.4: Minimal activity6

Why Enzymatic Oxygen Removal is Unique

E

Catalytic Regeneration

Unlike stoichiometric chemical reducing agents, the enzyme catalyzes continuous oxygen reduction as long as substrate is available.10 One enzyme molecule can process thousands of O₂ molecules.

O₂

Substrate Specificity

Cytochrome oxidase exhibits high specificity for molecular oxygen.11 Does not reduce other oxidizing agents or interfere with cellular redox reactions beyond oxygen removal.

4e⁻

No Reactive Intermediates

Complete 4-electron reduction of O₂ to H₂O without releasing superoxide (O₂⁻), hydrogen peroxide (H₂O₂), or hydroxyl radicals (OH·).12 Eliminates oxidative stress to cells.

B

Biomimetic Process

Uses the same electron transport mechanism present in all aerobic organisms.13 Compatible with biological systems since it mimics natural cellular respiration pathways.

ΔG

Thermodynamic Efficiency

Enzymatic catalysis lowers activation energy for O₂ reduction, enabling rapid oxygen removal at physiological temperatures without harsh chemical conditions.14

H₂O

Clean Chemistry

Terminal product is water only. No accumulation of oxidized sulfur species, disulfides, or other chemical byproducts that could interfere with biological processes.15

Comparison to Natural Respiration

Living Cells

Glucose oxidation

Electron transport chain

Cytochrome oxidase

O₂ → H₂O

Oxyrase® System

Substrate oxidation

Electron transport chain

Cytochrome oxidase

O₂ → H₂O

Scientific Discovery and Development

1981
Initial Discovery at Oak Ridge National Laboratory

Dr. Howard Adler and colleagues discover that sterile bacterial cytoplasmic membrane fragments containing intact electron transport chains can enzymatically reduce oxygen to water. Published in Biotechnology and Bioengineering Symposium.1

1984
Patent Issued for Enzyme System

US Patent 4,476,224 awarded for “Material and Method for Promoting the Growth of Anaerobic Bacteria” – describing the enzymatic oxygen removal mechanism and membrane fragment preparation.2

1990-2000
Mechanistic Studies Published

Multiple peer-reviewed studies elucidate the enzymatic pathway, substrate specificity, cofactor requirements, and comparison to chemical reducing agents. Crystal structure of d-lactate dehydrogenase published in PNAS.3

2000s
Expanded Applications Research

Scientific publications document enzyme system applications beyond microbiology: fluorescence microscopy (preventing photobleaching), cell preservation, pharmaceutical antioxidant, and biochemical research tool. Over 1,500 citations in peer-reviewed literature.19

2025
Continuing Research

Ongoing studies on enzyme variants from different bacterial sources (Acetobacter aceti for acidic pH applications), optimization of membrane preparation methods, and novel applications in cancer therapy and biotechnology.19

Learn More About the Oxyrase® Enzyme System

Explore the science behind enzymatic oxygen removal and discover how this technology is being applied across diverse fields of research.

Questions about the enzyme mechanism? Email info@oxyrase.com

References

  1. Adler, H.W., et al. (1981). “A material and method for the enzymatic removal of oxygen from systems.” Biotechnology and Bioengineering Symposium 11:373-384. View full citation
  2. Adler, H.W. & Crow, W.B. (1984). “Material and Method for Promoting the Growth of Anaerobic Bacteria.” US Patent 4,476,224. Patent details
  3. Decker, K. et al. (2000). “The crystal structure of d-lactate dehydrogenase, a peripheral membrane respiratory enzyme.” Proceedings of the National Academy of Sciences 97(17):9413-9418. Related papers
  4. Oxyrase Inc. Technical Documentation. “Substrate Requirements for Optimal Enzyme Activity.” Product inserts
  5. Yagi, T. (1991). “Bacterial NADH-quinone oxidoreductases.” Journal of Bioenergetics and Biomembranes 23(2):211-225. Related research
  6. Oxyrase Inc. Technical Bulletin. “pH and Temperature Optimization for Oxyrase® Enzyme System.” Technical bulletins
  7. Copeland, J.P. & Adler, H.W. (1990). “Temperature-dependent activity of respiratory enzymes in membrane preparations.” Journal of Rapid Methods and Automation in Microbiology 6(2):115-132. Full article
  8. Spangler, S.K. & Appelbaum, P.C. (1993). “Use of Oxyrase for macrolide and azalide susceptibility testing.” Journal of Clinical Microbiology 31(4):823-827. View publication
  9. Berg, J.M., Tymoczko, J.L. & Stryer, L. (2002). “Oxidative phosphorylation.” In: Biochemistry, 5th edition. New York: W.H. Freeman. Section 18.4.
  10. Oxyrase Inc. White Paper. “Enzymatic vs. Chemical Oxygen Removal: Mechanistic Comparison.” Read white paper
  11. Yoshikawa, S. et al. (1998). “Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase.” Science 280(5370):1723-1729. Related research
  12. Proshlyakov, D.A. et al. (1998). “Direct measurement of oxygen binding to cytochrome c oxidase.” Proceedings of the National Academy of Sciences 95(14):8020-8025. Scientific papers
  13. Mitchell, P. (1961). “Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism.” Nature 191(4784):144-148.
  14. Nicholls, D.G. & Ferguson, S.J. (2013). Bioenergetics 4. Academic Press. Chapter 3: “The Chemiosmotic Proton Circuit.”
  15. Copeland, J.P. et al. (1995). “Comparison of enzymatic and chemical reducing agents for anaerobic microbiology.” Anaerobe 1(5):269-276. Comparison studies
  16. Oxyrase Inc. Technical Specifications. “Enzyme Activity Standards and Measurement Protocols.” Technical specs
  17. Oxyrase Inc. Safety Data Sheet. “EC-Oxyrase® Storage and Handling.” View SDS
  18. Luo, J.K. & Diosady, L.L. (2020). “Effect of combination of Oxyrase and sodium thioglycolate on growth of Clostridium perfringens from spores.” Food Microbiology 91:103535. View study
  19. Google Scholar Citations Database. “Oxyrase Enzyme System – Over 1,500 peer-reviewed citations.” Browse all citations

Additional Resources

For a complete list of over 1,500 peer-reviewed publications citing the Oxyrase® Enzyme System, visit our Literature Citations page.

Technical documentation, product inserts, and safety data sheets are available in our Technical Information section.

White papers and comparison studies can be found at White Papers.

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