In accordance with the basic laws of physics, all living things need energy from the environment in some form in order to sustain life. Clearly, different organisms have evolved various means of harvesting fuel from various sources to power the cellular machinery that drives everyday processes such as growth, repair and reproduction.
Plants and animals obviously do not acquire food (or its equivalent in organisms that cannot actually "eat" anything) by similar means, and their respective innards do not digest molecules extracted from fuel sources in remotely the same way. Some organisms require oxygen for survival, others are killed by it, and still others can tolerate it but function well in its absence.
Despite the range of strategies living things employ to extract energy from the chemical bonds in carbon-rich compounds, the series of ten metabolic reactions collectively termed glycolysis are common to virtually all cells, both in prokaryotic organisms (almost all of which are bacteria) and in eukaryotic organisms (mostly plants, animals and fungi).
Glycolysis: Reactants and Products
An overview of the major inputs and outputs of glycolysis is a good starting point for understanding how cells go about converting molecules gathered from the external world to energy for sustaining the myriad life processes in which your body's cells are continually engaged.
Glycolysis reactants are often listed glucose and oxygen, while water, carbon dioxide and ATP (adenosine triphosphate, the molecule living most commonly use to power cellular processes) are given as glycolysis products, as follows:
C6H12O6 + 6 O2 --> 6 CO2 + 6 H2O + 36 (or 38) ATP
Calling this "glycolysis," as some texts do, is incorrect. This is the net reaction of aerobic respiration as a whole, of which glycolysis is the initial step. As you'll see in detail, the products of glycolysis per se are actually pyruvate and a modest amount of energy in the form of ATP:
C6H12O6 --> 2 C3H4O3 + 2 ATP + 2 NADH + 2 H+
NADH, or NAD+ in its de-protonated state (nicotinamide adenine dinucleotide), is a so-called high-energy electron carrier and an intermediate in many cellular reactions involved in energy release. Note two things here: One is that glycolysis alone is not nearly as efficient at releasing ATP as is complete aerobic respiration, in which the pyruvate produced in glycolysis enter the Krebs cycle en route to those carbon atoms landing in the electron transport chain. Whereas glycolysis takes place in the cytoplasm, the subsequent reactions of aerobic respiration occur in cellular organelles called mitochondria.
Glycolysis: Initial Steps
Glucose, which contains a six-ring structure that includes five carbon atoms and one oxygen atom, is shuttled into the cell across the plasma membrane by specialized transport proteins. Once inside, it is immediately phosphorylated, i.e., a phosphate group is attached to it. This does two things: It gives the molecule a negative charge, in effect trapping it within the cell (charged molecules cannot readily cross the plasma membrane) and it destabilizes the molecule, setting it up to me more reality broken down into smaller components.
The new molecule is called glucose-6-phosphate (G-6-P), since the phosphate group is attached to the number-6 carbon atom of glucose (the only one that lies outside the ring structure). The enzyme that catalyzes this reaction is a hexokinase; "hex-" is Greek prefix for "six" (as in "six-carbon sugar") and kinases are enzymes that swipe a phosphate group from one molecule and pin it elsewhere; in this instance, the phosphate is taken from ATP, leaving ADP (adenosine diphosphate) in its wake.
The next step is the conversion of glucose-6-phosphate to fructose-6-phosphate (F-6-P). This is simply a rearrangement of atoms, or an isomerization, with no additions or subtractions, such that one of the carbon atoms within the glucose ring is moved outside the ring, leaving a five-atom ring in its place. (You may recall that fructose is "fruit sugar," a common and naturally occurring dietary element.) The enzyme catalyzing this reaction is phosphoglucose isomerase.
The third step is another phosphorylation, catalyzed by phosphofructokinase (PFK) and yielding fructose 1,6-bisphosphate (F-1,6-BP). Here, the second phosphate group is joined to the carbon atom that was pulled out of the ring in the preceding step. (Chemistry nomenclature tip: The reason this molecule is called "bisphosphate" rather than "diphosphate" is that the two phosphates are joined to different carbon atoms, rather than one being joined to the other opposite a carbon-phosphate linkage.) In this as well as the previous phosphorylation step, the phosphate supplied comes from a molecule of ATP, so these early glycolysis steps require an investment of two ATP.
The fourth step of glycolysis breaks a now-highly unstable six-carbon molecule into two different three-carbon molecules: glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP). Aldolase is the enzyme responsible for this cleavage. You can discern from the names of these three-carbon molecules that each one of them gets one of the phosphates from the parent molecule.
Glycolysis: Final Steps
With glucose having been manipulated and divided into roughly equal pieces owing to a small input of energy, the remaining reactions of glycolysis involve the reclaiming of the phosphates in a way that results in a net energy gain. The basic reason that this occurs is that removing phosphate groups from these compounds is more energetically favorable than simply taking them from ATP molecules directly and applying them to other purposes; think of the initial steps of glycolysis in terms of an old adage – "You have to spend money too make money."
Like G-6-P and F-6-P, GAP and DHAP are isomers: They have the same molecular formula, but different physical structures. As it happens, GAP lies on the direct chemical pathway between glucose and pyruvate, while DHAP does not. Therefore, in the fifth step of glycolysis, an enzyme called triose phosphate isomerase (TIM) takes charge and converts DHAP to GAP. This enzyme is described as one of the most efficient in all of human energy metabolism, speeding up the reaction it catalyzes by a factor of roughly ten billion (1010).
In the sixth step, GAP is converted to 1,3-bisphosphoglycerate (1,3-BPG) under the influence of the enzyme by glyceraldehyde 3-phosphate dehydrogenase. Dehydrogenase enzymes do exactly what their names suggest – they remove hydrogen atoms (or protons, if you prefer). The hydrogen liberated from GAP finds its way to a molecule of NAD+, yielding NADH. Bear in mind that beginning with this step, for accounting purposes, everything is multiplied by two, since the initial molecule of glucose becomes two molecules of GAP. Thus after this step, two NAD+ molecules have been reduced to two molecules of NADH.
The de facto reversal of the earlier phosphorylation reactions of glycolysis begins with the seventh step. Here, the enzyme phosphoglycerate kinase removes a phosphate from 1,3-BPG to yield 3-phosphoglycerate (3-PG), with the phosphate landing on ADP to form ATP. Since, again, this involves two 1,3-BOG molecules for every glucose molecule that enters glycolysis upstream, this means that two ATPs are produced overall, canceling out the two ATPs invested in steps one and three.
In step eight, 3-PG is converted to 2-phosphoglycerate (2-PG) thanks to phosphoglycerate mutase, which extracts the remaining phosphate group and moves it one carbon over. Mutase enzymes differ from isomerases in that, rather than significantly rearranging the structure of a whole molecule, they merely shift one "residue" (in this case, a phosphate group) to a new location while leaving the overall structure intact.
In step nine, however, this preservation of structure is rendered moot, as 2-PG is converted to phosphoenol pyruvate (PEP) by the enzyme enolase. An enol is a combination og an alk_ene_ and and an alcohol. Alkenes are hydrocarbons that include a carbon-carbon double bond, while alcohols are hydrocarbons with a hydroxyl group (-OH) appended. The -OH in the case of an enol is attached to one of the carbons involved in the carbon-carbon double bond of PEP.
Finally, in the tenth and final step of glycolysis, PEP is converted to pyruvate by the enzyme pyruvate kinase. If you suspect from the names of the various actors in this step that another two molecules of ATP are generated in the process (one per actual reaction), you are correct. The phosphate group is removed from PEP and appended to ADP lurking nearby, yielding ATP and pyruvate. Pyruvate is a ketone, meaning that is has a non-terminal carbon (that is, one that is not at the end of the molecule) involved in a double bond with oxygen and two single bonds with other carbon atoms. The chemical formula for pyruvate is C3H4O3, but expressing this as (CH3)CO(COOH) offers a more illuminating picture of the final product of glycolysis.
Energy Considerations and the Fate of Pyruvate
The total amount energy liberated (it is tempting but wrong to say "produced," as energy "production" is a misnomer) is conveniently expressed as two ATP per molecule of glucose. But to be more mathematically precise, this is also 88 kilojoules per mole (kJ/mol) of glucose, equal to about 21 kilocalories per mole (kcal/mol). A mole of a substance is the mass of that substance that contains Avogadro's number of molecules, or 6.02 ×1023 molecules. The molecular mass of glucose is just over 180 grams.
Since, as noted previously, aerobic respiration can derive well over 30 molecules of ATP per glucose invested, it is tempting to regard the energy production of glycolysis alone as trivial, almost worthless. This is completely untrue. Consider that bacteria, which have been around for close to three and a half billion years, can get by quite nicely using glycolysis alone, because these are exquisitely simple life forms that have few of the requirements eukaryotic organisms do.
In fact, it is possible to view aerobic respiration differently by standing the whole scheme on its head: While this kind of energy production is certainly a biochemical and evolutionary marvel, organisms that make use of it for the most part absolutely rely on it. This means that when oxygen is nowhere to be found, organisms that rely exclusively or heavily on aerobic metabolism – that is, every organism reading this discussion – cannot survive for long in the absence of oxygen.
In any event, most of the pyruvate produced in glycolysis moves into the mitochondrial matrix (analogous to the cytoplasm of whole cells) and enters the Krebs cycle, also called the citric acid cycle or the tricarboxylic acid cycle. This series of reactions serves primarily to generate a lot of high-energy electron carriers, both NADH and a related compound called FADH2, but also yields two ATP per original glucose molecule. These molecules then migrate to the mitochondrial membrane and participate in the electron transport chain reactions that ultimately liberate 34 more ATP.
In the absence of sufficient oxygen (such as when you are exercising strenuously), some of the pyruvate undergoes fermentation, a kind of anaerobic metabolism in which pyruvate is converted to lactic acid, generating more NAD+ for use in metabolic processes.
About the Author
Kevin Beck holds a bachelor's degree in physics with minors in math and chemistry from the University of Vermont. Formerly with ScienceBlogs.com and the editor of "Run Strong," he has written for Runner's World, Men's Fitness, Competitor, and a variety of other publications. More about Kevin and links to his professional work can be found at www.kemibe.com.