Introduction
Cellular respiration is one of the most elegant, majestic, and fascinating metabolic pathways on earth. At the same time, it’s also one of the most complicated. When I learned about it for the first time, I felt like I had tripped and fallen into a can of organic-chemistry-flavored alphabet soup!
Luckily, cellular respiration is not so scary once you get to know it. Let's start by looking at cellular respiration at a high level, walking through the four major stages and tracing how they connect up to one another.
Steps of cellular respiration
Overview of the steps of cellular respiration.
1. Glycolysis. Six-carbon glucose is converted into two pyruvates (three carbons each). ATP and NADH are made. These reactions take place in the cytosol.
2. Pyruvate oxidation. Pyruvate travels into the mitochondrial matrix and is converted to a two-carbon molecule bound to coenzyme A, called acetyl CoA. Carbon dioxide is released and NADH is made.
3. Citric acid cycle. The acetyl CoA combines with a four-carbon molecule and goes through a cycle of reactions, ultimately regenerating the four-carbon starting molecule. ATP (or, in some cases, GTP), NADH, and FADH_2 are made, and carbon dioxide is released. These reactions take place in the mitochondrial matrix.
4. Oxidative phosphorylation. The NADH and FADH_2 produced in other steps deposit their electrons in the electron transport chain in the inner mitochondrial membrane. As electrons move down the chain, energy is released and used to pump protons out of the matrix and into the intermembrane space, forming a gradient. The protons flow back into the matrix through an enzyme called ATP synthase, making ATP. At the end of the electron transport chain, oxygen accepts electrons and takes up protons to form water.
Overview of the steps of cellular respiration.
Glycolysis. Six-carbon glucose is converted into two pyruvates (three carbons each). ATP and NADH are made. These reactions take place in the cytosol.
Pyruvate oxidation. Pyruvate travels into the mitochondrial matrix and is converted to a two-carbon molecule bound to coenzyme A, called acetyl CoA. Carbon dioxide is released and NADH is made.
Citric acid cycle. The acetyl CoA combines with a four-carbon molecule and goes through a cycle of reactions, ultimately regenerating the four-carbon starting molecule. ATP (or, in some cases, GTP), NADH, and FADH_2 are made, and carbon dioxide is released. These reactions take place in the mitochondrial matrix.
Oxidative phosphorylation. The NADH and FADH_2 produced in other steps deposit their electrons in the electron transport chain in the inner mitochondrial membrane. As electrons move down the chain, energy is released and used to pump protons out of the matrix and into the intermembrane space, forming a gradient. The protons flow back into the matrix through an enzyme called ATP synthase, making ATP. At the end of the electron transport chain, oxygen accepts electrons and takes up protons to form water.
During cellular respiration, a glucose molecule is gradually broken down into carbon dioxide and water. Along the way, some ATP is produced directly in the reactions that transform glucose. Much more ATP, however, is produced later in a process called oxidative phosphorylation. Oxidative phosphorylation is powered by the movement of electrons through the electron transport chain, a series of proteins embedded in the inner membrane of the mitochondrion.
These electrons come originally from glucose and are shuttled to the electron transport chain by electron carriers \text{NAD}^+NAD
+
start text, N, A, D, end text, start superscript, plus, end superscript and \text{FAD}FADstart text, F, A, D, end text, which become \text{NADH}NADHstart text, N, A, D, H, end text and \text{FADH}_2FADH
2
start text, F, A, D, H, end text, start subscript, 2, end subscript when they gain electrons. To be clear, this is what's happening in the diagram above when it says ++plus \text {NADH}NADHstart text, N, A, D, H, end text or ++plus \text{FADH}_2FADH
2
start text, F, A, D, H, end text, start subscript, 2, end subscript. The molecule isn't appearing from scratch, it's just being converted to its electron-carrying form:
\text {NAD}^+NAD
+
start text, N, A, D, end text, start superscript, plus, end superscript ++plus 2 e^-2e
−
2, e, start superscript, minus, end superscript ++plus 2 \text H^+2H
+
2, start text, H, end text, start superscript, plus, end superscript \rightarrow→right arrow \text {NADH}NADHstart text, N, A, D, H, end text ++plus \text H^+H
+
start text, H, end text, start superscript, plus, end superscript
\text {FAD}FADstart text, F, A, D, end text ++plus 2e^-2e
−
2, e, start superscript, minus, end superscript ++plus 2 \text H^+2H
+
2, start text, H, end text, start superscript, plus, end superscript \rightarrow→right arrow \text {FADH}_2FADH
2
