8.2: Catabolism of Carbohydrates - Biology

Learning Objectives

  • Describe why glycolysis is not oxygen dependent
  • Define and describe the net yield of three-carbon molecules, ATP, and NADH from glycolysis
  • Explain how three-carbon pyruvate molecules are converted into two-carbon acetyl groups that can be funneled into the Krebs cycle.
  • Define and describe the net yield of CO2, GTP/ATP, FADH2, and NADH from the Krebs cycle
  • Explain how intermediate carbon molecules of the Krebs cycle can be used in a cell

Extensive enzyme pathways exist for breaking down carbohydrates to capture energy in ATP bonds. In addition, many catabolic pathways produce intermediate molecules that are also used as building blocks for anabolism. Understanding these processes is important for several reasons. First, because the main metabolic processes involved are common to a wide range of chemoheterotrophic organisms, we can learn a great deal about human metabolism by studying metabolism in more easily manipulated bacteria like E. coli. Second, because animal and human pathogens are also chemoheterotrophs, learning about the details of metabolism in these bacteria, including possible differences between bacterial and human pathways, is useful for the diagnosis of pathogens as well as for the discovery of antimicrobial therapies targeting specific pathogens. Last, learning specifically about the pathways involved in chemoheterotrophic metabolism also serves as a basis for comparing other more unusual metabolic strategies used by microbes. Although the chemical source of electrons initiating electron transfer is different between chemoheterorophs and chemoautotrophs, many similar processes are used in both types of organisms.

The typical example used to introduce concepts of metabolism to students is carbohydrate catabolism. For chemoheterotrophs, our examples of metabolism start with the catabolism of polysaccharides such as glycogen, starch, or cellulose. Enzymes such as amylase, which breaks down glycogen or starch, and cellulases, which break down cellulose, can cause the hydrolysis of glycosidic bonds between the glucose monomers in these polymers, releasing glucose for further catabolism.


For bacteria, eukaryotes, and most archaea, glycolysis is the most common pathway for the catabolism of glucose; it produces energy, reduced electron carriers, and precursor molecules for cellular metabolism. Every living organism carries out some form of glycolysis, suggesting this mechanism is an ancient universal metabolic process. The process itself does not use oxygen; however, glycolysis can be coupled with additional metabolic processes that are either aerobic or anaerobic. Glycolysis takes place in the cytoplasm of prokaryotic and eukaryotic cells. It begins with a single six-carbon glucose molecule and ends with two molecules of a three-carbon sugar called pyruvate. Pyruvate may be broken down further after glycolysis to harness more energy through aerobic or anaerobic respiration, but many organisms, including many microbes, may be unable to respire; for these organisms, glycolysis may be their only source of generating ATP.

The type of glycolysis found in animals and that is most common in microbes is the Embden-Meyerhof-Parnas (EMP) pathway, named after Gustav Embden (1874–1933), Otto Meyerhof (1884–1951), and Jakub Parnas (1884–1949). Glycolysis using the EMP pathway consists of two distinct phases (Figure (PageIndex{1})). The first part of the pathway, called the energy investment phase, uses energy from two ATP molecules to modify a glucose molecule so that the six-carbon sugar molecule can be split evenly into two phosphorylated three-carbon molecules called glyceraldehyde 3-phosphate (G3P). The second part of the pathway, called the energy payoff phase, extracts energy by oxidizing G3P to pyruvate, producing four ATP molecules and reducing two molecules of NAD+ to two molecules of NADH, using electrons that originated from glucose. (A discussion and illustration of the full EMP pathway with chemical structures and enzyme names appear in Appendix C.)

The ATP molecules produced during the energy payoff phase of glycolysis are formed by substrate-level phosphorylation (Figure (PageIndex{1})), one of two mechanisms for producing ATP. In substrate-level phosphorylation, a phosphate group is removed from an organic molecule and is directly transferred to an available ADP molecule, producing ATP. During glycolysis, high-energy phosphate groups from the intermediate molecules are added to ADP to make ATP.

Overall, in this process of glycolysis, the net gain from the breakdown of a single glucose molecule is:

  • two ATP molecules
  • two NADH molecule, and
  • two pyruvate molecules.

Other Glycolytic Pathways

When we refer to glycolysis, unless otherwise indicated, we are referring to the EMP pathway used by animals and many bacteria. However, some prokaryotes use alternative glycolytic pathways. One important alternative is the Entner-Doudoroff (ED) pathway, named after its discoverers Nathan Entner and Michael Doudoroff (1911–1975). Although some bacteria, including the opportunistic gram-negative pathogen Pseudomonas aeruginosa, contain only the ED pathway for glycolysis, other bacteria, like E. coli, have the ability to use either the ED pathway or the EMP pathway.

A third type of glycolytic pathway that occurs in all cells, which is quite different from the previous two pathways, is the pentose phosphate pathway (PPP) also called the phosphogluconate pathway or the hexose monophosphate shunt. Evidence suggests that the PPP may be the most ancient universal glycolytic pathway. The intermediates from the PPP are used for the biosynthesis of nucleotides and amino acids. Therefore, this glycolytic pathway may be favored when the cell has need for nucleic acid and/or protein synthesis, respectively. A discussion and illustration of the complete ED pathway and PPP with chemical structures and enzyme names appear in Appendix C.

Exercise (PageIndex{1})

When might an organism use the ED pathway or the PPP for glycolysis?

Transition Reaction, Coenzyme A, and the Krebs Cycle

Glycolysis produces pyruvate, which can be further oxidized to capture more energy. For pyruvate to enter the next oxidative pathway, it must first be decarboxylated by the enzyme complex pyruvate dehydrogenase to a two-carbon acetyl group in the transition reaction, also called the bridge reaction (see Appendix C and Figure (PageIndex{3})). In the transition reaction, electrons are also transferred to NAD+ to form NADH. To proceed to the next phase of this metabolic process, the comparatively tiny two-carbon acetyl must be attached to a very large carrier compound called coenzyme A (CoA). The transition reaction occurs in the mitochondrial matrix of eukaryotes; in prokaryotes, it occurs in the cytoplasm because prokaryotes lack membrane-enclosed organelles.

The Krebs cycle transfers remaining electrons from the acetyl group produced during the transition reaction to electron carrier molecules, thus reducing them. The Krebs cycle also occurs in the cytoplasm of prokaryotes along with glycolysis and the transition reaction, but it takes place in the mitochondrial matrix of eukaryotic cells where the transition reaction also occurs. The Krebs cycle is named after its discoverer, British scientist Hans Adolf Krebs (1900–1981) and is also called the citric acid cycle, or the tricarboxylic acid cycle (TCA) because citric acid has three carboxyl groups in its structure. Unlike glycolysis, the Krebs cycle is a closed loop: The last part of the pathway regenerates the compound used in the first step (Figure (PageIndex{4})). The eight steps of the cycle are a series of chemical reactions that capture the two-carbon acetyl group (the CoA carrier does not enter the Krebs cycle) from the transition reaction, which is added to a four-carbon intermediate in the Krebs cycle, producing the six-carbon intermediate citric acid (giving the alternate name for this cycle). As one turn of the cycle returns to the starting point of the four-carbon intermediate, the cycle produces two CO2 molecules, one ATP molecule (or an equivalent, such as guanosine triphosphate [GTP]) produced by substrate-level phosphorylation, and three molecules of NADH and one of FADH2. (A discussion and detailed illustration of the full Krebs cycle appear in Appendix C.)

Although many organisms use the Krebs cycle as described as part of glucose metabolism, several of the intermediate compounds in the Krebs cycle can be used in synthesizing a wide variety of important cellular molecules, including amino acids, chlorophylls, fatty acids, and nucleotides; therefore, the cycle is both anabolic and catabolic (Figure (PageIndex{5})).

Key Concepts and Summary

  • Glycolysis is the first step in the breakdown of glucose, resulting in the formation of ATP, which is produced by substrate-level phosphorylation; NADH; and two pyruvate molecules. Glycolysis does not use oxygen and is not oxygen dependent.
  • After glycolysis, a three-carbon pyruvate is decarboxylated to form a two-carbon acetyl group, coupled with the formation of NADH. The acetyl group is attached to a large carrier compound called coenzyme A.
  • After the transition step, coenzyme A transports the two-carbon acetyl to the Krebs cycle, where the two carbons enter the cycle. Per turn of the cycle, one acetyl group derived from glycolysis is further oxidized, producing three NADH molecules, one FADH2, and one ATP by substrate-level phosphorylation, and releasing two CO2molecules.
  • The Krebs cycle may be used for other purposes. Many of the intermediates are used to synthesize important cellular molecules, including amino acids, chlorophylls, fatty acids, and nucleotides.

Multiple Choice

During which of the following is ATP not made by substrate-level phosphorylation?

A. Embden-Meyerhof pathway
B. Transition reaction
C. Krebs cycle
D. Entner-Doudoroff pathway


Which of the following products is made during Embden-Meyerhof glycolysis?

B. pyruvate
C. CO2
D. two-carbon acetyl


During the catabolism of glucose, which of the following is produced only in the Krebs cycle?



Which of the following is not a name for the cycle resulting in the conversion of a two-carbon acetyl to one ATP, two CO2, one FADH2, and three NADH molecules?

A. Krebs cycle
B. tricarboxylic acid cycle
C. Calvin cycle
D. citric acid cycle



Glycolysis requires oxygen or another inorganic final electron acceptor to proceed.


Fill in the Blank

Per turn of the Krebs cycle, one acetyl is oxidized, forming ____ CO2, ____ ATP, ____ NADH, and ____ FADH2molecules.

2; 1; 3; 1

Most commonly, glycolysis occurs by the ________ pathway.


Short Answer

What is substrate-level phosphorylation? When does it occur during the breakdown of glucose to CO2?

Why is the Krebs cycle important in both catabolism and anabolism?

Critical Thinking

What would be the consequences to a cell of having a mutation that knocks out coenzyme A synthesis?

Medical Definition of Carbohydrates

Carbohydrates: Mainly sugars and starches, together constituting one of the three principal types of nutrients used as energy sources (calories) by the body. Carbohydrates can also be defined chemically as neutral compounds of carbon, hydrogen and oxygen.

Carbohydrates come in simple forms such as sugars and in complex forms such as starches and fiber. The body breaks down most sugars and starches into glucose, a simple sugar that the body can use to feed its cells. Complex carbohydrates are derived from plants. Dietary intake of complex carbohydrates can lower blood cholesterol when they are substituted for saturated fat.

Carbohydrates are classified into mono, di, tri, poly and heterosaccharides. The smallest carbohydrates are monosaccharides such as glucose whereas polysaccharides such as starch, cellulose and glycogen can be large and even indeterminate in length.

The energy produced by carbohydrates is 4 calories per gram. Proteins also provide 4 calories per gram. Fats are high-cal they provide 9 calories per gram.

Etymology: Carbohydrates are called carbohydrates because the carbon, hydrogen and oxygen they contain are usually in the proportion to form water with the general formula Cn(H2O)n.

Catabolism of the Last Two Steroid Rings in Mycobacterium tuberculosis and Other Bacteria

Most mycolic acid-containing actinobacteria and some proteobacteria use steroids as growth substrates, but the catabolism of the last two steroid rings has yet to be elucidated. In Mycobacterium tuberculosis, this pathway includes virulence determinants and has been proposed to be encoded by the KstR2-regulated genes, which include a predicted coenzyme A (CoA) transferase gene (ipdAB) and an acyl-CoA reductase gene (ipdC). In the presence of cholesterol, ΔipdC and ΔipdAB mutants of either M. tuberculosis or Rhodococcus jostii strain RHA1 accumulated previously undescribed metabolites: 3aα-H-4α(carboxyl-CoA)-5-hydroxy-7aβ-methylhexahydro-1-indanone (5-OH HIC-CoA) and (R)-2-(2-carboxyethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA (COCHEA-CoA), respectively. A ΔfadE32 mutant of Mycobacterium smegmatis accumulated 4-methyl-5-oxo-octanedioic acid (MOODA). Incubation of synthetic 5-OH HIC-CoA with purified IpdF, IpdC, and enoyl-CoA hydratase 20 (EchA20), a crotonase superfamily member, yielded COCHEA-CoA and, upon further incubation with IpdAB and a CoA thiolase, yielded MOODA-CoA. Based on these studies, we propose a pathway for the final steps of steroid catabolism in which the 5-member ring is hydrolyzed by EchA20, followed by hydrolysis of the 6-member ring by IpdAB. Metabolites accumulated by ΔipdF and ΔechA20 mutants support the model. The conservation of these genes in known steroid-degrading bacteria suggests that the pathway is shared. This pathway further predicts that cholesterol catabolism yields four propionyl-CoAs, four acetyl-CoAs, one pyruvate, and one succinyl-CoA. Finally, a ΔipdAB M. tuberculosis mutant did not survive in macrophages and displayed severely depleted CoASH levels that correlated with a cholesterol-dependent toxicity. Our results together with the developed tools provide a basis for further elucidating bacterial steroid catabolism and virulence determinants in M. tuberculosis.IMPORTANCE Bacteria are the only known steroid degraders, but the pathway responsible for degrading the last two steroid rings has yet to be elucidated. In Mycobacterium tuberculosis, this pathway includes virulence determinants. Using a series of mutants in M. tuberculosis and related bacteria, we identified a number of novel CoA thioesters as pathway intermediates. Analysis of the metabolites combined with enzymological studies establishes how the last two steroid rings are hydrolytically opened by enzymes encoded by the KstR2 regulon. Our results provide experimental evidence for novel ring-degrading enzymes, significantly advance our understanding of bacterial steroid catabolism, and identify a previously uncharacterized cholesterol-dependent toxicity that may facilitate the development of novel tuberculosis therapeutics.

Keywords: CoA thioester Mycobacterium tuberculosis catabolism cholesterol ring opening.

Copyright © 2017 Crowe et al.


HIP catabolic genes in representative…

HIP catabolic genes in representative actinobacteria and proteobacteria. (A) The aerobic catabolism and…

Growth of Δ ipdAB M. tuberculosis . WT M. tuberculosis Erdman (black), Δ…

Growth of Δ ipdC R. jostii RHA1. WT RHA1::pTipQC2 (black), Δ ipdC RHA1::pTipQC2…

Accumulation of cholesterol-derived metabolites from…

Accumulation of cholesterol-derived metabolites from Δ ipdAB and Δ ipdC strains. (A) GC-MS…

LC-MS analyses of the transformation…

LC-MS analyses of the transformation of 5-OH HIC-CoA by purified enzymes. The left…

Cholesterol-derived metabolite of Δ fadE32…

Cholesterol-derived metabolite of Δ fadE32 M. smegmatis . (A) GC-MS traces of culture…

Characterization of KstR2 regulon mutants…

Characterization of KstR2 regulon mutants of M. smegmatis . Growth of Δ echA20…

Cholesterol-dependent toxicity. (A) Growth of…

Cholesterol-dependent toxicity. (A) Growth of WT (black), Δ ipdAB (red), and Δ ipdAB…

Proposed HIP catabolic pathway. NMR-confirmed…

Proposed HIP catabolic pathway. NMR-confirmed metabolites are in blue. Metabolites for which MS…

Biology of glucose metabolization in cancer cells

Cancer is a disease at the cellular level involving heritable disorders in cellular control mechanism. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumor microenvironment. Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. They alter their metabolism to support their rapid proliferation and expansion across the body. After the discovery of based on the altered cancer cell metabolism in 1930, loads of studies have shed light on several aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. Research has directed most of its resources to elucidate the causes, prevention and possible cure for cancer, yet the process has been elusive claiming human lives more than ever. This disease is a manifestation of etiological and pathological disturbances of mechanisms that control cell division, differentiation and metabolism. 50% of all human tumors carry genetic alterations that lead to the inactivation of some tumor suppressor proteins. Cancer cells are shown to experience characteristic changes in their metabolic programs, including increased uptake of glucose, enhanced rates of glutaminolysis and fatty acids synthesis, suggesting that metabolic shifts supports tumor cells growth and survival. In this review, we summarized the major concepts of glucose metabolization and explore the molecular basis of aerobic glycolysis of cancer cells.

38 Connections of Carbohydrate, Protein, and Lipid Metabolic Pathways

By the end of this section, you will be able to do the following:

  • Discuss the ways in which carbohydrate metabolic pathways, glycolysis, and the citric acid cycle interrelate with protein and lipid metabolic pathways
  • Explain why metabolic pathways are not considered closed systems

You have learned about the catabolism of glucose, which provides energy to living cells. But living things consume organic compounds other than glucose for food. How does a turkey sandwich end up as ATP in your cells? This happens because all of the catabolic pathways for carbohydrates, proteins, and lipids eventually connect into glycolysis and the citric acid cycle pathways (see (Figure)). Metabolic pathways should be thought of as porous and interconnecting—that is, substances enter from other pathways, and intermediates leave for other pathways. These pathways are not closed systems! Many of the substrates, intermediates, and products in a particular pathway are reactants in other pathways.

Connections of Other Sugars to Glucose Metabolism

Glycogen , a polymer of glucose, is an energy storage molecule in animals. When there is adequate ATP present, excess glucose is stored as glycogen in both liver and muscle cells. The glycogen will be hydrolyzed into glucose 1-phosphate monomers (G-1-P) if blood sugar levels drop. The presence of glycogen as a source of glucose allows ATP to be produced for a longer period of time during exercise. Glycogen is broken down into glucose-1-phosphate (G-1-P) and converted into glucose-6-phosphate (G-6-P) in both muscle and liver cells, and this product enters the glycolytic pathway.

Sucrose is a disaccharide with a molecule of glucose and a molecule of fructose bonded together with a glycosidic linkage. Fructose is one of the three “dietary” monosaccharides, along with glucose and galactose (part of the milk sugar dissacharide lactose), which are absorbed directly into the bloodstream during digestion. The catabolism of both fructose and galactose produces the same number of ATP molecules as glucose.

Connections of Proteins to Glucose Metabolism

Proteins are hydrolyzed by a variety of enzymes in cells. Most of the time, the amino acids are recycled into the synthesis of new proteins. If there are excess amino acids, however, or if the body is in a state of starvation, some amino acids will be shunted into the pathways of glucose catabolism ((Figure)). It is very important to note that each amino acid must have its amino group removed prior to entry into these pathways. The amino group is converted into ammonia. In mammals, the liver synthesizes urea from two ammonia molecules and a carbon dioxide molecule. Thus, urea is the principal waste product in mammals, produced from the nitrogen originating in amino acids, and it leaves the body in urine. It should be noted that amino acids can be synthesized from the intermediates and reactants in the cellular respiration cycle.

Connections of Lipid and Glucose Metabolisms

The lipids connected to the glucose pathway include cholesterol and triglycerides. Cholesterol is a lipid that contributes to cell membrane flexibility and is a precursor of steroid hormones. The synthesis of cholesterol starts with acetyl groups and proceeds in only one direction. The process cannot be reversed.

Triglycerides—made from the bonding of glycerol and three fatty acids—are a form of long-term energy storage in animals. Animals can make most of the fatty acids they need. Triglycerides can be both made and broken down through parts of the glucose catabolism pathways. Glycerol can be phosphorylated to glycerol-3-phosphate, which continues through glycolysis. Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl groups are picked up by CoA to form acetyl CoA that proceeds into the citric acid cycle.

Pathways of Photosynthesis and Cellular Metabolism The processes of photosynthesis and cellular metabolism consist of several very complex pathways. It is generally thought that the first cells arose in an aqueous environment—a “soup” of nutrients—possibly on the surface of some porous clays, perhaps in warm marine environments. If these cells reproduced successfully and their numbers climbed steadily, it follows that the cells would begin to deplete the nutrients from the medium in which they lived as they shifted the nutrients into the components of their own bodies. This hypothetical situation would have resulted in natural selection favoring those organisms that could exist by using the nutrients that remained in their environment and by manipulating these nutrients into materials upon which they could survive. Selection would favor those organisms that could extract maximal value from the nutrients to which they had access.

An early form of photosynthesis developed that harnessed the sun’s energy using water as a source of hydrogen atoms, but this pathway did not produce free oxygen (anoxygenic photosynthesis). (Another type of anoxygenic photosynthesis did not produce free oxygen because it did not use water as the source of hydrogen ions instead, it used materials such as hydrogen sulfide and consequently produced sulfur). It is thought that glycolysis developed at this time and could take advantage of the simple sugars being produced but that these reactions were unable to fully extract the energy stored in the carbohydrates. The development of glycolysis probably predated the evolution of photosynthesis, as it was well suited to extract energy from materials spontaneously accumulating in the “primeval soup.” A later form of photosynthesis used water as a source of electrons and hydrogen and generated free oxygen. Over time, the atmosphere became oxygenated, but not before the oxygen released oxidized metals in the ocean and created a “rust” layer in the sediment, permitting the dating of the rise of the first oxygenic photosynthesizers. Living things adapted to exploit this new atmosphere that allowed aerobic respiration as we know it to evolve. When the full process of oxygenic photosynthesis developed and the atmosphere became oxygenated, cells were finally able to use the oxygen expelled by photosynthesis to extract considerably more energy from the sugar molecules using the citric acid cycle and oxidative phosphorylation.

Section Summary

The breakdown and synthesis of carbohydrates, proteins, and lipids connect with the pathways of glucose catabolism. The simple sugars are galactose, fructose, glycogen, and pentose. These are catabolized during glycolysis. The amino acids from proteins connect with glucose catabolism through pyruvate, acetyl CoA, and components of the citric acid cycle. Cholesterol synthesis starts with acetyl groups, and the components of triglycerides come from glycerol-3-phosphate from glycolysis and acetyl groups produced in the mitochondria from pyruvate.


When we began talking about low-carbohydrate diets in class, student body language indicated increased interest (sitting up straight, leaning forward, increased eye contact, asking questions). Students reported having conversations with their friends and families on the topic. A typical comment was “My dad wants me to tell him everything I learn about this.” I also heard statements that I had never heard before, such as “I love metabolism.” While we did not do rigorous assessment of learning before and after using this approach, there was considerable anecdotal evidence that including this highly relevant application of metabolic principles was helpful in motivating students to learn and to provide them with additional familiarity to assist in retention of learning.

Summary of several metabolic pathways. Glycolysis and fatty acid oxidation both produce acetyl CoA. Acetyl CoA can enter the citric acid cycle or be degraded via ketosis, among other fates. Concept for drawing inspired from Bhagavan's Medical Biochemistry [ 1 ].

Watch the video: IB Biology Cell Respiration (January 2022).