Daily Newsletter

September 24, 2013

Redox and Coupled Reactions

Energy harvesting will be our topic next week, so I wanted to spend a moment and talk about energy in biological systems. Energy is a word that is often thrown around in various disciplines, and most of us carry misconceptions about the world from colloquial (common) use of the word. Scientists define energy as the capacity to do work. This definition helps to simplify a complex issue, but it starts to get confused when we apply it to the complex sets of reactions that we see in living systems.
For example, as we saw yesterday, the work in phosphorylation occurs in creating the covalent bond between a phosphate group and a substrate, not the action of the substrate. With ATP, the emphasis was shifted from seeing ATP as a battery that powered reactions. Instead, your focus was drawn to the Phosphate group, and the electrostatic effect it would have when added to a molecule or protein.

Next week we will discuss Energy Harvesting. Like with ATP, I want you to focus your attention on a specific form of energy, instead of holding a nebulous concept. Today the focus will be on reducing potential. Central metabolism describes the oxidation of glucose, so what are we harvesting? Reducing potential. So what is reducing potential?

A simple definition is reducing potential describes the capacity of a compound to donate electrons. Chemistry has a strict definition involving measurements with electrodes, but for our purpose, the concept of donating electrons is what is important.

Remember the characteristics of life. You must maintain homeostasis, and this means repair. You have to build nucleic acids, lipids, carbohydrates and proteins. These biosynthetic pathways often require you to reduce substrates. To stay alive, you need a constant supply of electrons for reduction; you need reducing potential. If you don't get these high energy electrons for reduction, you die. We will also find that this reducing potential is needed for us to make ATP.

Redox reactions are vital to our survival. Redox reactions are coupled Oxidation and Reduction reactions. One compound is oxidized as the next is reduced.

Remember, the molecules undergoing redox have to be close/touching. But in relative size, a cell is huge compared to a simple molecule. We may harvest electrons (oxidation) in one part of the cell, but use the harvested reducing potential in another part of the cell (reduction). Remember, you don't have free electrons; you can't throw electrons across the cytoplasm. So, how do we couple reactions that may be separated spatially? We use carriers!

Electron carriers, like nicotinamide adenine dinucleotide (NAD⁺), accept electrons at the site of oxidation, and then donate electrons at the site of reduction. NAD⁺ is readily oxidized and reduced during metabolic reactions, and there is only a negligible loss of energy from the electrons carried (can we ever have NO loss of energy? why or why not?).
NAD⁺ is also classified as a coenzyme, meaning it must work with an enzyme to accept or donate electrons. NAD⁺ can not randomly go to a molecule and oxidize or reduce it; its action is regulated by enzymes. NAD⁺ then must bind to an enzyme that catalyzes an Oxidation, and NADH must bind to an enzyme that catalyzes a Reduction.

Specifically, we couple the reactions. NAD⁺ has a place to bind into the enzyme, many times next to the substrate. The NAD⁺ can then capture the eletron pair that is released from the substrate. Additionally, one of the hydrogens will bind to the electron carrier. When we move to the next reaction, NADH will bind with an enzyme, again normally next to the substrate in question. The NADH can then donate the electrons (and hydrogens to the substrate. Enzymes thus help to couple these reactions. NAD⁺ will not just pick up an electron from any source, and NADH will not just donate electrons to any source. It must be mediated by enzymes.

Daily Challenge

Action of nicotinamide adenine dinucleotide (NAD)
In the citric acid cycle is the following reaction:

In this reaction, malate is oxidized. How do you know? You know because NAD is reduced to NADH. Below is a ribbon model of the protein malate dehydrogenase. Within the protein, you will see two molecules of NAD represented as balls. NAD binds to the enzymes active site first, and then malate binds. Within the active site are both + and - amino acids.

Your task today, using the enzyme malate dehydrogenase, explain how enzymes work and explain how reducing potential is harvested from organic compounds.