How to Metabolize Glucose to Make ATP

How to Metabolize Glucose to Make ATP
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Glucose, a six-carbon sugar, is the fundamental "input" in the equation that powers all of life. Energy from the outside is, by some means, converted to energy for the cell. Every organism that is alive, from your best friend to the lowliest bacterium, has cells that burn glucose for fuel at the root metabolic level.

Organisms differ in the extent to which their cells can extract energy from glucose. In all cells, this energy is in the form of adenosine triphosphate (ATP).

Therefore, one thing all living cells have in common is that they metabolize glucose to make ATP. A given glucose molecule entering a cell could have begun as a steak dinner, as the prey of a wild animal, as plant matter or as something else.

Regardless, various digestive and biochemical processes have broken down all of the multi-carbon molecules in whatever substances the organism ingests for nourishment to the monosaccharide sugar that enters cellular metabolic pathways.

What Is Glucose?

Chemically, glucose is a hexose sugar, hex being the Greek prefix for "six," the number of carbon atoms in glucose. Its molecular formula is C6H12O6, giving it a molecular weight of 180 grams per mole.

Glucose is also a monosaccharide in that is is a sugar that includes only one fundamental unit, or monomer. Fructose is another example of a monosaccharide, while sucrose, or table sugar (fructose plus glucose), lactose (glucose plus galactose) and maltose (glucose plus glucose) are disaccharides.

Note that the ratio of carbon, hydrogen and oxygen atoms in glucose is 1:2:1. All carbohydrates, in fact, show this same ratio, and their molecular formulas are all of the form CnH2nOn.

What Is ATP?

ATP is a nucleoside, in this case adenosine, with three phosphate groups attached to it. This actually makes it a nucleotide, as a nucleoside is a pentose sugar (either ribose or deoxyribose) combined with a nitrogenous base (i.e., adenine, cytosine, guanine, thymine or uracil), whereas a nucleotide is a nucleoside with one or more phosphate groups attached. But terminology aside, the important thing to know about ATP is that it contains adenine, ribose and a chain of three phosphate (P) groups.

ATP is made via the phosphorylation of adenosine diphosphate (ADP), and conversely, when the terminal phosphate bond in ATP is hydrolyzed, ADP and Pi (inorganic phosphate) are the products. ATP is considered the "energy currency" of cells as this extraordinary molecule is used to power almost every metabolic process.

Cellular Respiration

Cellular respiration is the set of metabolic pathways in eukaryotic organisms that converts glucose to ATP and carbon dioxide in the presence of oxygen, giving off water and producing a wealth of ATP (36 to 38 molecules per glucose molecule invested) in the process.

The balanced chemical formula for the overall net reaction, excluding electron carriers and energy molecules, is:

C6H12O6 + 6 O2 → 6 CO2 + 6 H2O

Cellular respiration actually includes three distinct and sequential pathways:

  • Glycolysis, which occurs in all cells and takes place in the cytoplasm, and is always the first step of glucose metabolism (and in most prokaryotes, also the last step).
  • The Krebs cycle, also called the tricarboxylic acid (TCA) cycle or the citric acid cycle, which unfolds in the mitochondrial matrix.
  • The electron transport chain, which takes place on the inner mitochondrial membrane and generates most of the ATP produced in cellular respiration.

The latter two of these stages are oxygen-dependent and together make up aerobic respiration. Often, however, in discussions of eukaryotic metabolism, glycolysis, though it does not depend on oxygen, is considered to be part "aerobic respiration" because almost all of its main product, pyruvate, goes on to enter the other two pathways.

Early Glycolysis

In glycolysis, glucose is converted in a series of 10 reactions into the molecule pyruvate, with a net gain of two molecules of ATP and two molecules of the "electron carrier" nicotinamide adenine dinucleotide (NADH). For every molecule of glucose entering the process, two molecules of pyruvate are produced, as pyruvate has three carbon atoms to glucose's six.

In the first step, glucose is phosphorylated to become glucose-6-phosphate (G6P). This commits the glucose to being metabolized rather than drifting back out through the cell membrane, because the phosphate group gives G6P a negative charge. Over the next few steps, the molecule is rearranged into a different sugar derivative and then phosphorylated a second time to become fructose-1,6-bisphosphate.

These early steps of glycolysis require an investment of two ATP because this is the source of the phosphate groups in the phosphorylation reactions.

Later Glycolysis

The fructose-1,6-bisphosphate splits into two different three-carbon molecules, each bearing its own phosphate group; almost all of one of these, is quickly converted to the other, glyceraldehyde-3-phosphate (G3P). Thus from this point forward, everything is duplicated because there are two G3P for every glucose "upstream."

From this point, G3P is phosphorylated in a step that also produces NADH from the oxidized form NAD+, and then the two phosphate groups are given up to ADP molecules in subsequent rearrangement steps to produce two ATP molecules along with the end carbon product of glycolysis, pyruvate.

Since this happens twice per glucose molecule, the second half of glycolysis produces four ATP for a net gain from glycolysis of two ATP (since two were required early in the process) and two NADH.

The Krebs Cycle

In the preparatory reaction, after the pyruvate generated in glycolysis finds its way from the cytoplasm into the mitochondrial matrix, it is converted first to acetate (CH3COOH-) and CO2 (a waste product in this scenario) and then to a compound called acetyl coenzyme A, or acetyl CoA. In this reaction, an NADH is generated. This sets the stage for the Krebs cycle.

This series of eight reactions is so named because one of the reactants in the first step, oxaloacetate, is also the product in the last step. The job of the Krebs cycle is that of a supplier rather than a manufacturer: It generates only two ATP per glucose molecule, but contributes six more NADH and two of FADH2, another electron carrier and a close relative of NADH.

(Note that this means one ATP, three NADH and one FADH2 per turn of the cycle. For every glucose that enters glycolysis, two molecules of acetyl CoA enter the Krebs cycle.)

The Electron Transport Chain

On a per-glucose basis, the energy tally to this point is four ATP (two from glycolysis and two from the Krebs cycle), 10 NADH (two from glycolysis, two from the preparatory reaction and six from the Krebs cycle) and two FADH2 from the Krebs cycle. While the carbon compounds in the Krebs cycle continue to spin around upstream, the electron carriers move from the mitochondrial matrix to the mitochondrial membrane.

When NADH and FADH2 release their electrons, these are used to create an electrochemical gradient across the mitochondrial membrane. This gradient is used to power the attachment of phosphate groups to ADP to create ATP in a process called oxidative phosphorylation, so named because the ultimate acceptor of the electrons cascading from electron carrier to electron carrier in the chain is oxygen (O2).

Because each NADH yields three ATP and each FADH2 yields two ATP in oxidative phosphorylation, this adds (10)(3) + (2)(2) = 34 ATP to the mix. Thus one molecule of glucose can yield up to 38 ATP in eukaryotic organisms.

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