Glycolysis

Importance of Glycolysis

Glycolysis is the first step in the breakdown of glucose to extract energy for cellular metabolism.

Learning Objectives

Explain the importance of glycolysis to cells

Key Takeaways

Key Points

  • Glycolysis is present in nearly all living organisms.
  • Glucose is the source of almost all energy used by cells.
  • Overall, glycolysis produces two pyruvate molecules, a net gain of two ATP molecules, and two NADH molecules.

Key Terms

  • glycolysis: the cellular metabolic pathway of the simple sugar glucose to yield pyruvic acid and ATP as an energy source
  • heterotroph: an organism that requires an external supply of energy in the form of food, as it cannot synthesize its own
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Cellular Respiration: Glycolysis is the first pathway of cellular respiration that oxidizes glucose molecules. It is followed by the Krebs cycle and oxidative phosphorylation to produce ATP.

Nearly all of the energy used by living cells comes to them from the energy in the bonds of the sugar glucose. Glucose enters heterotrophic cells in two ways. One method is through secondary active transport in which the transport takes place against the glucose concentration gradient. The other mechanism uses a group of integral proteins called GLUT proteins, also known as glucose transporter proteins. These transporters assist in the facilitated diffusion of glucose. Glycolysis is the first pathway used in the breakdown of glucose to extract energy. It takes place in the cytoplasm of both prokaryotic and eukaryotic cells. It was probably one of the earliest metabolic pathways to evolve since it is used by nearly all of the organisms on earth. The process does not use oxygen and is, therefore, anaerobic.

Glycolysis is the first of the main metabolic pathways of cellular respiration to produce energy in the form of ATP. Through two distinct phases, the six-carbon ring of glucose is cleaved into two three-carbon sugars of pyruvate through a series of enzymatic reactions. The first phase of glycolysis requires energy, while the second phase completes the conversion to pyruvate and produces ATP and NADH for the cell to use for energy. Overall, the process of glycolysis produces a net gain of two pyruvate molecules, two ATP molecules, and two NADH molecules for the cell to use for energy. Following the conversion of glucose to pyruvate, the glycolytic pathway is linked to the Krebs Cycle, where further ATP will be produced for the cell’s energy needs.

Electron Donors and Acceptors

Electrons can enter the electron transport chain at three levels: dehydrogenase, the quinone pool, or a mobile cytochromeelectron carrier.

Learning Objectives

Recognize the various types of electron donors and acceptors

Key Takeaways

Key Points

  • Bacterial electron transport chains may contain as many as three proton pumps.
  • The most common electron donors are organic molecules.
  • There are a number of different electron acceptors, both organic and inorganic. If oxygen is available, it is invariably used as the terminal electron acceptor.

Key Terms

  • organotroph: An organism that obtains its energy from organic compounds.
  • lithotroph: An organism that obtains its energy from inorganic compounds (such as ammonia) via electron transfer.

In prokaryotes ( bacteria and archaea there are several different electron donors and several different electron acceptors. Note that electrons can enter the chain at three levels: at the level of a dehydrogenase, at the level of the quinone pool, or at the level of a mobile cytochrome electron carrier. These levels correspond to successively more positive redox potentials, or to successively decreased potential differences relative to the terminal electron acceptor. In other words, they correspond to successively smaller Gibbs free energy changes for the overall redox reaction Donor → Acceptor.

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Glycolysis Pathway Overview: An overview of the glycolytic pathway. This pathway, comprised of a series of reactions, produces many intermediates and molecules utilized as substrates for biosynthesis in additional pathways.

Individual bacteria use multiple electron transport chains, often simultaneously. Bacteria can use a number of different electron donors, a number of different dehydrogenases, a number of different oxidases and reductases, and a number of different electron acceptors. For example, E. coli (when growing aerobically using glucose as an energy source) uses two different NADH dehydrogenases and two different quinol oxidases, for a total of four different electron transport chains operating simultaneously.

A common feature of all electron transport chains is the presence of a proton pump to create a transmembrane proton gradient. Bacterial electron transport chains may contain as many as three proton pumps, like mitochondria, or they may contain only one or two. They always contain at least one proton pump.

In the present day biosphere, the most common electron donors are organic molecules. Organisms that use organic molecules as an energy source are called organotrophs. Organotrophs (animals, fungi, protists) and phototrophs (plants and algae) constitute the vast majority of all familiar life forms.

Some prokaryotes can use inorganic matter as an energy source. Such organisms are called lithotrophs (“rock-eaters”). Inorganic electron donors include hydrogen, carbon monoxide, ammonia, nitrite, sulfur, sulfide, and ferrous iron. Lithotrophs have been found growing in rock formations thousands of meters below the surface of Earth. Because of their volume of distribution, lithotrophs may actually out number organotrophs and phototrophs in our biosphere.

The use of inorganic electron donors as an energy source is of particular interest in the study of evolution. This type of metabolism must logically have preceded the use of organic molecules as an energy source.

Just as there are a number of different electron donors (organic matter in organotrophs, inorganic matter in lithotrophs), there are a number of different electron acceptors, both organic and inorganic. If oxygen is available, it is invariably used as the terminal electron acceptor, because it generates the greatest Gibbs free energy change and produces the most energy.

In anaerobic environments, different electron acceptors are used, including nitrate, nitrite, ferric iron, sulfate, carbon dioxide, and small organic molecules such as fumarate.

Since electron transport chains are redox processes, they can be described as the sum of two redox pairs. For example, the mitochondrial electron transport chain can be described as the sum of the NAD+/NADH redox pair and the O2/H2O redox pair. NADH is the electron donor and O2 is the electron acceptor.

Not every donor-acceptor combination is thermodynamically possible. The redox potential of the acceptor must be more positive than the redox potential of the donor. Furthermore, actual environmental conditions may be far different from standard conditions (1 molar concentrations, 1 atm partial pressures, pH = 7), which apply to standard redox potentials. For example, hydrogen-evolving bacteria grow at an ambient partial pressure of hydrogen gas of 10-4 atm. The associated redox reaction, which is thermodynamically favorable in nature, is thermodynamically impossible under “standard” conditions.

Bacterial electron transport pathways are, in general, inducible. Depending on their environment, bacteria can synthesize different transmembrane complexes and produce different electron transport chains in their cell membranes. Bacteria select their electron transport chains from a DNA library containing multiple possible dehydrogenases, terminal oxidases and terminal reductases. The situation is often summarized by saying that electron transport chains in bacteria are branched, modular, and inducible.

ATP Yield

The amount of energy (as ATP) gained from glucose catabolism varies across species and depends on other related cellular processes.

Learning Objectives

Describe the origins of variability in the amount of ATP that is produced per molecule of glucose consumed

Key Takeaways

Key Points

  • While glucose catabolism always produces energy, the amount of energy (in terms of ATP equivalents) produced can vary, especially across different species.
  • The number of hydrogen ions the electron transport chain complexes can pump through the membrane varies between species.
  • NAD+ provides more ATP than FAD+ in the electron transport chain and can lead to variance in ATP production.
  • The use of intermediates from glucose catabolism in other biosynthetic pathways, such as amino acid synthesis, can lower the yield of ATP.

Key Terms

  • catabolism: Destructive metabolism, usually including the release of energy and breakdown of materials.

ATP Yield

In a eukaryotic cell, the process of cellular respiration can metabolize one molecule of glucose into 30 to 32 ATP. The process of glycolysis only produces two ATP, while all the rest are produced during the electron transport chain. Clearly, the electron transport chain is vastly more efficient, but it can only be carried out in the presence of oxygen.

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Cellular respiration in a eukaryotic cell: Glycolysis on the left portion of this illustration can be seen to yield 2 ATP molecules, while the Electron Transport Chain portion at the upper right will yield the remaining 30-32 ATP molecules under the presence of oxygen.

The number of ATP molecules generated via the catabolism of glucose can vary substantially. For example, the number of hydrogen ions the electron transport chain complexes can pump through the membrane varies between species. Another source of variance occurs during the shuttle of electrons across the membranes of the mitochondria. The NADH generated from glycolysis cannot easily enter mitochondria. Thus, electrons are picked up on the inside of mitochondria by either NAD+ or FAD+. These FAD+ molecules can transport fewer ions; consequently, fewer ATP molecules are generated when FAD+ acts as a carrier. NAD+ is used as the electron transporter in the liver, and FAD+ acts in the brain.

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Adenosine triphosphate: ATP is the main source of energy in many living organisms.

Another factor that affects the yield of ATP molecules generated from glucose is the fact that intermediate compounds in these pathways are used for other purposes. Glucose catabolism connects with the pathways that build or break down all other biochemical compounds in cells, but the result is not always ideal. For example, sugars other than glucose are fed into the glycolytic pathway for energy extraction. Moreover, the five-carbon sugars that form nucleic acids are made from intermediates in glycolysis. Certain nonessential amino acids can be made from intermediates of both glycolysis and the citric acid cycle. Lipids, such as cholesterol and triglycerides, are also made from intermediates in these pathways, and both amino acids and triglycerides are broken down for energy through these pathways. Overall, in living systems, these pathways of glucose catabolism extract about 34 percent of the energy contained in glucose.

Respiration and Proton Motive Force

Respiration is one of the key ways a cell gains useful energy to fuel cellular activity.

Learning Objectives

Describe the role of the proton motive force in respiration

Key Takeaways

Key Points

  • The reactions involved in respiration are catabolic reactions, which break large molecules into smaller ones, releasing energy in the process as they break high-energy bonds.
  • Aerobic respiration requires oxygen in order to generate energy ( ATP ).
  • Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism (which yields two molecules ATP per one molecule glucose).
  • With the help of the solar-driven enzyme bacteriorhodopsin, some bacteria make proton gradients by pumping in protons from the environment.

Key Terms

  • exothermic: releasing energy in the form of heat
  • redox: a reversible process in which one reaction is an oxidation and the reverse is a reduction

Cellular Respiration

Cellular respiration is a set of metabolic reactions and processes that take place within the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate (ATP). The reactions involved in this respiration are considered to be catabolic reactions that release energy as larger molecules are broken down into smaller ones and high-energy bonds are broken. Respiration is one of the key ways a cell gains useful energy to fuel cellular activity.

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Overview of Cellular Respiration: A diagram of cellular respiration including glycolysis, Krebs cycle (AKA citric acid cycle), and the electron transport chain.

Chemically, cellular respiration is considered an exothermic redox reaction. The overall reaction is broken into many smaller ones when it occurs in the body. Most of these smaller reactions are redox reactions themselves. Although technically, cellular respiration is a combustion reaction, it does not resemble one when it occurs in a living cell. This is because it occurs in many separate steps. While the overall reaction is a combustion reaction, no single reaction that comprises it is a combustion reaction.

Aerobic and Anaerobic Reactions

Aerobic reactions require oxygen for ATP generation. Although carbohydrates, fats and proteins can be used as reactants, the preferred method is the process of glycolysis. During glycolysis, pyruvate is formed from glucose metabolism. During aerobic conditions, the pyruvate enters the mitochondrion to be fully oxidized by the Krebs cycle. The products of the Krebs cycle include energy in the form of ATP (via substrate level phosphorylation ), NADH, and FADH2.

The simplified reaction is as follows:

C6H12O6 (s) + 6 O2 (g) → 6 CO2 (g) + 6 H2O (l) + heat

ΔG = -2880 kJ per mole of C6H12O6

A negative ΔG indicates that the reaction can occur spontaneously.

Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism, which yields two molecules ATP per one molecule glucose. Both types of metabolism share the initial pathway of glycolysis, but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. In eukaryotic cells, the post-glycolytic reactions take place in the mitochondria, while in prokaryotic cells, these reactions take place in the cytoplasm.

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Humans use of prokaryotes: This is a microscopic image of Bacillus subtilis (ATCC 6633) with a gram staining of magnification: 1,000. The oval, unstained structures are spores.

Glycolysis

Glycolysis takes place in the cytosol, does not require oxygen, and can therefore function under anaerobic conditions. The process converts one molecule of glucose into two molecules of pyruvate, generating energy in the form of two net molecules of ATP. Four molecules of ATP per glucose are actually produced, but two of these are consumed as part of the preparatory phase. The initial phosphorylation of glucose is required to destabilize the molecule for cleavage into two pyruvate. During the pay-off phase of glycolysis, four phosphate groups are transferred to ADP by substrate-level phosphorylation to make four ATP, and two NADH are produced when the pyruvate are oxidized. The overall reaction can be expressed this way:

Glucose + 2 NAD+ + 2 Pi + 2 ADP → 2 pyruvate + 2 NADH + 2 ATP + 2 H+ + 2 H2O + heat

Starting with glucose, one ATP is used to donate a phosphate to glucose to produce glucose 6-phosphate. With the help of glycogen phosphorylase, glycogen can change into glucose 6-phosphate as well. During energy metabolism, glucose 6-phosphate turns into fructose 6-phosphate. With the help of phosphofructokinase, an additional ATP can be used to turn phosphorylate fructose 6-phosphate into fructose 1, 6-diphosphate. Fructose 1, 6-diphosphate then splits into two phosphorylated molecules with three carbon chains that later degrades into pyruvate.

Making Proton Gradients

Some archaea, the most notable ones being halobacteria, make proton gradients by pumping in protons from the environment. They are able to do this with the help of the solar-driven enzyme bacteriorhodopsin, which is used to drive the molecular motor enzyme ATP synthase to make the necessary conformational changes required to synthesize ATP. By running ATP synthase in reverse, proton gradients are also made by bacteria and are used to drive flagella. The F1FO ATP synthase is a reversible enzyme. Large enough quantities of ATP cause it to create a transmembrane proton gradient. This is used by fermenting bacteria, which lack an electron transport chain, and which hydrolyze ATP to make a proton gradient. Bacteria use these gradients for flagella and for the transportation of nutrients into the cell. In respiring bacteria under physiological conditions, ATP synthase, in general, runs in the opposite direction. This creates ATP while using the proton motive force created by the electron transport chain as a source of energy. The overall process of creating energy in this fashion is termed oxidative phosphorylation.