Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online

CHAPTER 8 - OXIDATION/PHOSPHORYLATION 

B:  OXIDATIVE ENZYMES

BIOCHEMISTRY - DR. JAKUBOWSKI

 04/15/16

Learning Goals/Objectives for Chapter 8B:  After class and this reading, students will be able to

  • state the type of oxidizing reagent used and the products forms on oxidation reactions catalyzed by dehydrogenases, monoxygenases (hydroxylases), dioxygenases, and oxidases;
  • draw the reactive end of NAD+ and mechanisms showing it's reactions with substrates in enzyme-catalyzed two electron oxidation reactions;
  • explain differences in chemical reactivity of NAD+ and FAD in one and two electrons oxidations and with dioxygen;
  • describe the stereochemistry of the alcohol dehydrogenase-catalyzed oxidation of prochiral ethanol by NAD+;
  • explain why FAD/FADH2 are often tightly bound to dehydrogenases in contrast to NAD+/NADH where are freely diffusable substrates;
  • given standard reduction potentials, determine the ΔGo' for given redox reactions;
  • explain why different FAD and other flavin containing dehydrogenases have varying standard reduction potentials for the flavin but NAD+ dependent dehydrogenase have only one;
  • describe the role of heme in mono- and dioxygenases in activating dioxygen and minimizing side reactions of ROSs;
  • describe the biological role of cytochrome P450s;
  • define and give examples of oxidases;
  • compare the contrast the role of the heme in carrying hemoglobin and myoglobin, monoxygenases, and in oxidases.

B1.  General Oxidizing Agents

Oxidizing agents are required to oxidize organic molecules. In organic lab, you never used dioxygen as an oxidizing agent. It is difficult to limit the extent of oxidation using dioxygen. In addition, side reactions are likely given the nature of the reactive oxygen reduction products. (The mechanisms of combustion reactions of organic molecules with dioxygen to produce carbon dioxide and water are very complicated.)  

Figure:  mechanisms of combustion reactions

INITIATION
CH4    -->  CH3.  + H .
O2    -->  2 O.

PROPAGATION
CH4   +  H .  -->  CH3.  +  H2
CH4   +  HO .  -->  CH3.  +  H2O
CH3.  +  O .  -->  CH2O  +  H.

CH2O  +  HO . ->  CHO.  +  H2O

 
CH2O  +  H . ->  CHO.  +  H2
CHO.   -->  CO  +  H.
CO  +   HO . ->  CO2  +  H.

BRANCHING

H.  +   O2    -->  HO.  +  O.

 

TERMINATION
H .  +   R.  +  M->    RH  +  M*

 

after Chemistry, 5th ed. Zumdahl. pg 1097

 In organic lab, other oxidizing agents are often used, including permanganate and chromate.

Figure:  permanganate

Figure:   chromate

Oxygen can often be inserted into a molecule in a nonoxidative process by hydration of an alkene to an alcohol (a readily reversible reaction), which could then be oxidized to either an aldehyde/ketone or carboxylic acid using an appropriate oxidizing agent.

Most biological oxidation reactions (such as those found in glycolysis, Kreb Cycle, and fatty acid oxidation) do not use dioxygen as the immediate oxidizing agent. Rather they use nicotinamide adeninine dinucleotide (NAD+) or flavin adenine dinucleotide (FAD) as oxidizing agents, which get reduced.  Enzymes that uses these oxidizing agents are usally called dehydrogenases.  Dioxygen can also be used to introduce oxygen atoms into biological molecules in oxidative reactions.   Enzymes that introduce one oxygen atom of dioxygen into a molecule (and the other oxygen into water) are called monooxygenases. (Note:  some monooxygenase that hydroxylate biomolecules are called hydroxylases.)  Those that introduce both atoms of dioxygen into a substrate are called dioxygenases. These oxygenases are not usually used to oxidize organic molecules for energy production. Rather they introduce O atoms for other reasons, including increasing the solubility of nonpolar aromatics to facilitate secretion, and to produce new molecular species which have different biological activities. Finally, biological molecules can be oxidized by dioxygen in which no atoms of oxygen are added to the substrate. Rather, electrons lost from the oxidized substrate are passed via intermediate electron carriers to dioxygen , which get reduced to superoxide (if  one electron is added), hydrogen peroxide (if two electrons are added) or water (if 4 electrons are added). These enzymes are called oxidases.   (Note:  The letters oxi- or oxygen- are used in all the enzymes that use dioxygen as the oxidizing agent.)

In this chapter section, we will discuss biological oxidation reactions. Most introductory biochemistry texts don't  approach oxidation reactions in one cohesive chapter.  Probably because of that, when I was learning biochemistry, I found the presentation of these different enzymes involved in redox reactions to be very confusing.   Hopefully this section  will alleviate that problem.  First the chemistry of NAD+ and FAD will be discussed. Then the enzymes using dioxygen in oxidative reactions (monooxygenases, dioxygenases, and oxidases) will be explored.

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