Life on Earth is extraordinarily diverse, from the tiniest bacteria living in thermal vents to the stately, multi-ton elephants that make their home in Asia. But all organisms (living things) have a number of basic characteristics in common, among them the need for molecules from which to derive energy. The process of extracting energy from external sources for growth, repair, maintenance and reproduction is known as metabolism.
All organisms consist of at least one cell (your own body includes trillions), which is the smallest irreducible entity that includes all of the properties ascribed to life using conventional definitions. Metabolism is one such property, as is the ability to replicate or otherwise reproduce. Every cell on the planet can and does make use of glucose, without which life on Earth would either never have come into being or would look very different.
The Chemistry of Glucose
Glucose has the formula C6H12O6, giving the molecule a molecular mass of 180 grams per mole. (All carbohydrates have the general formula CnH2nOn.) This makes glucose roughly the same size as the largest amino acids.
Glucose in nature exists as a six-atom ring, depicted as hexagonal in most texts. Five of the carbon atoms are included in the ring along with one of the oxygen atoms, while the sixth carbon atom is part of a hydroxymethyl group (-CH2OH) attached to one of the other carbons.
Amino acids, like glucose, are prominent monomers in biochemistry. Just as glycogen is assembled from long chains of glucose, proteins are synthesized from long chains of amino acids. While there are 20 distinct amino acids with numerous features in common, glucose comes in only one molecular form. Thus the composition of glycogen is essentially invariant, whereas proteins vary greatly from one to the next.
The Cellular Respiration Process
The metabolism of glucose to yield energy in the form of adenosine triphosphate (ATP) and CO2 (carbon dioxide, a waste product in this equation) is known as cellular respiration. The first of the three basic stages of cellular respiration is glycolysis, a series of 10 reactions that do not require oxygen, while the last two stages are the Krebs cycle (also known as the citric acid cycle) and the electron transport chain, which do require oxygen. Together, these last two stages are known as aerobic respiration.
Cellular respiration occurs almost entirely in eukaryotes (animals, plants and fungi). Prokaryotes (the mostly unicellular domains that include bacteria and archaea) derive energy from glucose, but virtually always from glycolysis alone. The implication is that prokaryotic cells can generate only about one-tenth the energy per molecule of glucose as eukaryotic cells can, as is detailed later.
"Cellular respiration" and "aerobic respiration" are often used interchangeably when discussing the metabolism of eukaryotic cells. It's understood that glycolysis, though an anaerobic process, almost invariably proceeds to the last two cellular respiration steps. Regardless, to sum up the role of glucose in cellular respiration: Without it, respiration stops and loss of life follows.
Enzymes and Cellular Respiration
Enzymes are globular proteins that act as catalysts in chemical reactions. This means that these molecules help speed along reactions that would otherwise still proceed without the enzymes, but far more slowly – sometimes by a factor of well over a thousand. When enzymes act, they are not changed themselves at the end of the reaction, whereas the molecules they act on, called substrates, are changed by design, with reactants such as glucose transformed into products such as CO2.
Glucose and ATP bear some chemical resemblance to each other, but using the energy stored in the bonds of the former molecule to power the synthesis of the latter molecule requires considerable biochemical acrobatics across the cell. Almost every cellular reaction is catalyzed by a specific enzyme, and most enzymes are specific for one reaction and its substrates. Glycolysis, the Krebs cycle and the electron transport chain, combined, feature about two dozen reactions and enzymes.
When glucose enters a cell by diffusing through the plasma membrane, it is immediately attached to a phosphate (P) group, or phosphorylated. This traps glucose in the cell owing to the negative charge of the P. This reaction, which produces glucose-6-phosphate (G6P), occurs under the influence of the enzyme hexokinase. (Most enzymes end in "-ase," making it fairly easy to know when you're dealing with one in the biology world.)
From there, G6P is rearranged into a phosphorylated type of the sugar fructose, and then another P is added. Soon afterward the six-carbon molecule is split into two three-carbon molecules, each with a phosphate group; these soon arrange themselves into the same substance, glyceraldehyde-3-phosphate (G-3-P).
Each molecule of G-3-P goes through a series of rearrangement steps to be converted into the three-carbon molocule pyruvate, producing two molecules of ATP and one molecule of the high-energy electron carrier NADH (reduced from nicotinamide adenine dinucleotide, or NAD+) in the process.
The first half of glycolysis consumes 2 ATP in the phosphorylation steps, while the second half yields a total of 2 pyruvate, 2 NADH and 4 ATP. In terms of direct energy production, glycolysis thus results in 2 ATP per glucose molecule. This, for most prokaryotes, represents the effective ceiling of glucose utilization. In eukaryotes, the glucose-cellular respiration show has only begun.
The Krebs Cycle
The pyruvate molecules then move from the cytoplasm of the cell to the inside of the organelles called mitochondria, which are enclosed by their own double plasma membrane. Here, the pyruvate is split into CO2 and acetate (CH3COOH-), and the acetate is grabbed by a compound from the B-vitamin class called coenzyme A (CoA) to become acetyl CoA, an important two-carbon intermediate in a range of cellular reactions.
To enter the Krebs cycle, the acetyl CoA reacts with the four-carbon compound oxaloacetate to form citrate. Because oxaloacetate is the last molecule created in the Krebs reaction as well as a substrate in the first reaction, the series earns the description "cycle." The cycle includes a total of eight reactions, which reduce the six-carbon citrate to a five-carbon molecule and then to a series of four-carbon intermediates before arriving again at oxaloacetate.
Energetics of the Krebs Cycle
Each molecule of pyruvate entering the Krebs cycle results in the production of two more CO2, 1 ATP, 3 NADH and one molecule of an electron carrier similar to NADH called flavin adenine dinucleotide, or FADH2.
- The Krebs cycle can only proceed if the electron transport chain is operating downstream to pick up the NADH and FADH2 it generates. Thus if no oxygen is available to the cell, the Krebs cycle halts.
The Electron Transport Chain
The NADH and FADH2 move to the inner mitochondrial membrane for this process. The role of the chain is the oxidative phosphorylation of ADP molecules to become ATP. The hydrogen atoms from the electron carriers are used to create an electrochemical gradient across the mitochondrial membrane. The energy from this gradient, which relies on oxygen to ultimately receive the electrons, is harnessed to power ATP synthesis.
Each molecule of glucose contributes anywhere from 36 to 38 ATP through cellular respiration: 2 in glycolysis, 2 in the Krebs cycle and 32 to 34 (depending on how this is measured in the lab) in the electron transport chain.