Substrates for Biosynthesis

Major metabolic pathways require substrates to be acted upon for the formation of larger, more complex products.

Learning Objectives

Describe the importance of substrates for biosynthesis

Key Takeaways

Key Points

  • Biogenesis or anabolism, requires substrates to be acted upon that result in the formation of larger more complex molecules.
  • A central metabolic pathway that produces precursors and substrates used in biosynthetic processes is the TCA cycle.
  • A central metabolic pathway that produces precursors and substrates used in biosynthetic processes is glycolysis.

Key Terms

  • reducing agent: A substance that functions in reducing or donating electrons to another substance until that specific substance becomes oxidized.
  • oxidation: A reaction in which the atoms of an element lose electrons and the valence of the element increases.

Microorganisms have numerous pathways and processes in place to ensure both energy and nutrient production. These pathways are necessary for survival and cellular function. The major metabolic pathways require substrates to be acted upon for the formation of larger, more complex products. Biosynthetic processes are defined by the production of more complex products that are required for growth and maintenance of life. These processes require pathways that are often multi-step. There are various components deemed necessary for biosynthetic processes to occur, including: precursor compounds, chemical energy, and carious catalytic enzymes.

TCA Cycle

The citric acid cycle, commonly referred to as the Krebs cycle, is characterized by the production of energy through the oxidation of acetate derived from carbohydrates, fats, and proteins into carbon dioxide. The cycle is one of the major metabolic processes utilized to generate energy. The citric acid cycle, comprised of a series of chemical reactions, provides precursors for additional biochemical pathways. These precursors are used as substrates for the biogenesis of large complex products. The precursors include amino acids and reducing agents such as NADH. Additional pathways that require precursors formed by the TCA include amino acid and nucleotide synthesis.


The Citric Acid Cycle: An overview of the Citric Acid Cycle.


An additional central metabolic pathway includes glycolysis. Glycolysis is characterized by a series of reactions that results in the conversion of glucose into pyruvate. This process is characterized by the production of various intermediates and molecules that function as substrates in additional pathways. Additional pathways that require substrates or metabolites produced by the glycolytic pathway include: gluconeogenesis, lipid metabolism, the pentose phosphate pathway, and the TCA.


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.

Biosynthesis and Energy

Biosynthetic processes ensure the production of complex products necessary for cellular and metabolic processes.

Learning Objectives

Discuss the principles of biosynthesis and provide examples

Key Takeaways

Key Points

  • Anabolism is the form of metabolism responsible for building large complexes from precursors.
  • The three categories of carbon fixation pathways are the Calvin cycle, the reverse TCA, and acetyl-CoA pathways.
  • One example of a biosynthetic process is gluconeogenesis, which is responsible for the production of glucose from noncarbohydrate precursors.

Key Terms

  • anabolism: Anabolism is the set of metabolic pathways that construct molecules from smaller units.
  • biosynthesis: Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products.
  • metabolic: Of or pertaining to metabolism; as, metabolic activity; metabolic force.

Biosynthesis and Energy

Biosynthesis in living organisms is a process in which substrates are converted to more complex products. The products which are produced as a result of biosynthesis are necessary for cellular and metabolic processes deemed essential for survival. Biosynthesis is often referred to as the anabolism branch of metabolism that results in complex proteins such as vitamins.


Overview of Gluconeogenesis: A biosynthetic pathway is utilized in microorganisms to produce glucose.

A majority of the organic compounds required by microorganisms are produced via biosynthetic pathways. The components which are utilized by biosynthetic pathways to promote the production of large molecules include chemical energy and catalytic enzymes. Biosynthetic building blocks utilized by organisms include amino acids, purines, pyrimidines, lipids, sugars, and enzyme cofactors. There are numerous mechanisms in place to ensure biosynthetic pathways are properly controlled so a cell will produce a specific amount of a compound. Biosynthetic metabolism (also known as anabolism) involves the synthesis of macromolecules from specific building blocks. A majority of these processes are considered to be multi-step or multi-enzymatic processes.

Carbon Dioxide Fixation

Carbon dioxide fixation is necessary to ensure carbon dioxide can be converted into organic carbon. The major pathways utilized to ensure fixation of carbon dioxide include: the Calvin cycle, the reductive TCA cycle, and the acetyl-CoA pathway. The Calvin cycle involves utilizing carbon dioxide and water to form organic compounds. The reductive TCA cycle, commonly referred to as the reverse Krebs cycle, also produces carbon compounds from carbon dioxide and water. In the acetyl-CoA pathway, carbon dioxide is reduced to carbon monoxide and then acetyl-CoA.

Glucose and Fructose Synthesis

An additional biosynthetic pathway utilized by microorganisms includes the synthesis of sugars and polysaccharides. The ability to synthesize sugars and polysaccharides from noncarbohydrate precursors is key to survival in numerous microorganisms. The process of gluconeogenesis, characterized by the production of glucose or fructose from noncarbohydrate precursors, is an ubiquitous process. This process utilizes precursors such as pyruvate, lactate, or glycerol.

The Calvin Cycle

The Calvin cycle is organized into three basic stages: fixation, reduction, and regeneration.

Learning Objectives

Describe the Calvin Cycle

Key Takeaways

Key Points

  • The Calvin cycle refers to the light-independent reactions in photosynthesis that take place in three key steps.
  • Although the Calvin Cycle is not directly dependent on light, it is indirectly dependent on light since the necessary energy carriers (ATP and NADPH) are products of light-dependent reactions.
  • In fixation, the first stage of the Calvin cycle, light-independent reactions are initiated; CO2 is fixed from an inorganic to an organic molecule.
  • In the second stage, ATP and NADPH are used to reduce 3-PGA into G3P; then ATP and NADPH are converted to ADP and NADP+, respectively.
  • In the last stage of the Calvin Cycle, RuBP is regenerated, which enables the system to prepare for more CO2 to be fixed.

Key Terms

  • light-independent reaction: chemical reactions during photosynthesis that convert carbon dioxide and other compounds into glucose, taking place in the stroma
  • rubisco: (ribulose bisphosphate carboxylase) a plant enzyme which catalyzes the fixing of atmospheric carbon dioxide during photosynthesis by catalyzing the reaction between carbon dioxide and RuBP
  • ribulose bisphosphate: an organic substance that is involved in photosynthesis, reacts with carbon dioxide to form 3-PGA

The Calvin Cycle

In plants, carbon dioxide (CO2) enters the leaves through stomata, where it diffuses over short distances through intercellular spaces until it reaches the mesophyll cells. Once in the mesophyll cells, CO2 diffuses into the stroma of the chloroplast, the site of light-independent reactions of photosynthesis. These reactions actually have several names associated with them. Other names for light-independent reactions include the Calvin cycle, the Calvin-Benson cycle, and dark reactions. The most outdated name is dark reactions, which can be misleading because it implies incorrectly that the reaction only occurs at night or is independent of light, which is why most scientists and instructors no longer use it.


Light Reactions: Light-dependent reactions harness energy from the sun to produce chemical bonds, ATP, and NADPH. These energy-carrying molecules are made in the stroma where the Calvin cycle takes place. The Calvin cycle is not totally independent of light since it relies on ATP and NADH, which are products of the light-dependent reactions.

The light-independent reactions of the Calvin cycle can be organized into three basic stages: fixation, reduction, and regeneration.


The Calvin Cycle: The Calvin cycle has three stages. In stage 1, the enzyme RuBisCO incorporates carbon dioxide into an organic molecule, 3-PGA. In stage 2, the organic molecule is reduced using electrons supplied by NADPH. In stage 3, RuBP, the molecule that starts the cycle, is regenerated so that the cycle can continue. Only one carbon dioxide molecule is incorporated at a time, so the cycle must be completed three times to produce a single three-carbon GA3P molecule, and six times to produce a six-carbon glucose molecule.

Stage 1: Fixation

In the stroma, in addition to CO2,two other components are present to initiate the light-independent reactions: an enzyme called ribulose bisphosphate carboxylase (RuBisCO) and three molecules of ribulose bisphosphate (RuBP). RuBP has five atoms of carbon, flanked by two phosphates. RuBisCO catalyzes a reaction between CO2 and RuBP. For each CO2 molecule that reacts with one RuBP, two molecules of 3-phosphoglyceric acid (3-PGA) form. 3-PGA has three carbons and one phosphate. Each turn of the cycle involves only one RuBP and one carbon dioxide and forms two molecules of 3-PGA. The number of carbon atoms remains the same, as the atoms move to form new bonds during the reactions (3 atoms from 3CO2 + 15 atoms from 3RuBP = 18 atoms in 3 atoms of 3-PGA). This process is called carbon fixation because CO2 is "fixed" from an inorganic form into organic molecules.

Stage 2: Reduction

ATP and NADPH are used to convert the six molecules of 3-PGA into six molecules of a chemical called glyceraldehyde 3-phosphate (G3P). This is a reduction reaction because it involves the gain of electrons by 3-PGA. Recall that a reduction is the gain of an electron by an atom or molecule. Six molecules of both ATP and NADPH are used. For ATP, energy is released with the loss of the terminal phosphate atom, converting it to ADP; for NADPH, both energy and a hydrogen atom are lost, converting it into NADP+. Both of these molecules return to the nearby light-dependent reactions to be reused and reenergized.

Stage 3: Regeneration

At this point, only one of the G3P molecules leaves the Calvin cycle and is sent to the cytoplasm to contribute to the formation of other compounds needed by the plant. Because the G3P exported from the chloroplast has three carbon atoms, it takes three "turns" of the Calvin cycle to fix enough net carbon to export one G3P. But each turn makes two G3Ps, thus three turns make six G3Ps. One is exported while the remaining five G3P molecules remain in the cycle and are used to regenerate RuBP, which enables the system to prepare for more CO2 to be fixed. Three more molecules of ATP are used in these regeneration reactions.

Intermediates Produced During the Calvin Cycle

The Calvin Cycle involves the process of carbon fixation to produce organic compounds necessary for metabolic processes.

Learning Objectives

Outline the function of the intermediates produced in the major phases of the Calvin Cycle

Key Takeaways

Key Points

  • The Calvin Cycle can be divided into three major phases: Phase 1: carbon fixation; Phase 2: reduction; Phase 3: regeneration.
  • The intermediates of the Calvin Cycle include ADP, NADP+, inorganic phosphate, and 3-phosphoglycerate.
  • Many of the intermediates or products of the Calvin Cycle are regenerated back into earlier stages of the process.

Key Terms

  • autotroph: Any organism that can synthesize its food from inorganic substances, using heat or light as a source of energy.
  • coenzyme: Any small molecule that is necessary for the functioning of an enzyme.
  • phosphorylation: The process of transferring a phosphate group from a donor to an acceptor; often catalysed by enzymes

The Calvin Cycle is characterized as a carbon fixation pathway. The Calvin Cycle is also referred to as the reductive pentose phosphate cycle or the Calvin-Benson-Bassham cycle. The process of carbon fixation involves the reduction of carbon dioxide to organic compounds by living organisms. The Calvin cycle is most often associated with carbon fixation in autotrophic organisms, such as plants, and is recognized as a dark reaction. In organisms that require carbon fixation, the Calvin cycle is a means to obtain energy and necessary components for growth. Some examples of microorganisms that utilize the Calvin cycle include cyanobacteria, purple bacteria, and nitrifying bacteria. Specifically, the Calvin cycle involves reducing carbon dioxide to the sugar triose phosphate, most commonly known as glyceraldehyde 3-phosphate (GAP). Throughout the Calvin Cycle, there are numerous intermediate molecules made which are consistently withdrawn and utilized to create cellular material and participate in cellular processes. The Calvin cycle can be divided into three major phases which include: Phase 1: carbon fixation; Phase 2: reduction; and Phase 3: regeneration of ribulose. The following is a brief overview of the intermediates created during the Calvin cycle.


The Calvin Cycle: An overview of the Calvin Cycle.

Phase 1: Carbon Fixation Intermediates

During phase 1 of this cycle, the CO2 molecule is incorporated into one of two 3-phosphoglycerate molecules (3-PGA). This process requires the enzyme RuBisCO and both ATP and NADPH. Once 3-PGA is formed, one of two molecules formed continues into the reduction phase (phase 2). The additional 3-PGA is utilized in additional metabolic pathways such as glycolysis and gluconeogenesis. The structure of 3-PGA allows it to be combined and rearranged to form sugars which can be transported to additional cells or stored for energy.

Phase 2: Reduction

During phase 2 of this cycle, the newly formed 3-PGA undergoes phosphorylation by the enzyme phosphoglycerate kinase which utilizes ATP. The result of this phosphorylation is the production of 1,3-bisphosphoglycerates and ADP products. The ADP product that is produced via the breakdown of ATP will be utilized in additional pathways and be converted back into ATP. The inter conversions of ATP to ADP and ADP to ATP is a key process in supplying energy in numerous processes. This energy is necessary for cellular growth and metabolic processes.

Once the bisphosphoglycerate molecules are formed, they must be converted and further reduced to GAP by NADPH. The intermediate of this product is the conversion of NADPH to NADP+ and an inorganic phosphate ion. NADP+ is a coenzyme which is necessary for the function of NADPH. The functions that require NADP+ include anabolic reactions such as lipid and nucleic acid synthesis. The inorganic phosphate ion is often a result of regulatory metabolic processes. The phosphate ions are used in processes such as buffering cells, conversions of AMP/ADP to ATP and production of materials involved in structure such as bone and teeth. It is important to note that these intermediates or products (inorganic phosphate, NADP+ and ADP) processed by phase 2 are often regenerated back into the cycle.

Phase 3: Regeneration of Ribulose

The GAP molecules at this point are the end product of the Calvin cycle, which is responsible for reducing carbon to a sugar form. However, additional GAP molecules that are formed will be converted to ribulose-1,5-bisphosphate (RuBP), which is responsible for the conversion of CO2 to 3-PGA in phase 1, via numerous steps. The G3P, which is destined to exit the cycle, will be used for carbohydrate synthesis and additional pathways.

Regulation of the Calvin Cycle

The Calvin cycle is a process that ensures carbon dioxide fixation in plants.

Learning Objectives

Outline the three major phases of the Calvin cycle: carbon fixation, reduction, and regeneration of ribulose

Key Takeaways

Key Points

  • In this process, carbon dioxide and water are converted into organic compounds that are necessary for metabolic and cellular processes.
  • The three phases of the Calvin cycle, fixation, reduction, and regeneration require specific enzymes to ensure proper regulation.
  • The last phase of the Calvin cycle, regeneration, is considered the most complex and regulated phase of the cycle.

Key Terms

  • calvin cycle: A series of biochemical reactions that take place in the stroma of chloroplasts in photosynthetic organisms.
  • gluconeogenesis: A metabolic process which glucose is formed from non-carbohydrate precursors.
  • ribulose: A ketopentose whose phosphate derivatives participate in photosynthesis.

The Calvin cycle is a process utilized to ensure carbon dioxide fixation. In this process, carbon dioxide and water are converted into organic compounds that are necessary for metabolic and cellular processes. There are various organisms that utilize the Calvin cycle for production of organic compounds including cyanobacteria and purple and green bacteria. The Calvin cycle requires various enzymes to ensure proper regulation occurs and can be divided into three major phases: carbon fixation, reduction, and regeneration of ribulose. Each of these phases are tightly regulated and require unique and specific enzymes.


Overview of the Calvin cycle: An overview of the Calvin cycle and the three major phases.

During the first phase of the Calvin cycle, carbon fixation occurs. The carbon dioxide is combined with ribulose 1,5-bisphosphate to form two 3-phosphoglycerate molecules (3-PG). The enzyme that catalyzes this specific reaction is ribulose bisphosphate carboxylase (RuBisCO). RuBisCO is identified as the most abundant enzyme on earth, to date. RuBisCO is the first enzyme utilized in the process of carbon fixation and its enzymatic activity is highly regulated. RuBisCO is only active during the day as its substrate, ribulose 1,5-bisphosphate, is not generated in the dark. RuBisCO enzymatic activity is regulated by numerous factors including: ions, RuBisCO activase, ATP /ADP and reduction/oxidation states, phosphate and carbon dioxide. The various factors influencing RuBisCO activity directly affect phase 1 of the Calvin cycle.

During the second phase of the Calvin cycle, reduction occurs. The 3-PG molecules synthesized in phase 1 are reduced to glyceraldehyde-3-phosphate (G3P). This reducing process is mediated by both ATP and NADPH. One of the two G3P molecules formed are further converted to dihydroxyacetone phosphate (DHAP) and the enzyme aldolase is used to combine G3P and DHAP to form fructose-1,6-bisphosphate. The enzyme aldolase is typically characterized as a glycolytic enzyme with the ability to split fructose 1,6-bisphosphate into DHAP and G3P. However, in this specific phase of the Calvin cycle, it is used in reverse. Therefore, aldolase is said to regulate a reverse reaction in the Calvin cycle. Additionally, aldolase can be utilized to promote a reverse reaction in gluconeogenesis as well. The fructose-1,6-bisphosphate formed in phase 2 is then converted into fructose-6-phosphate.

During the third phase of the Calvin cycle, regeneration of RuBisCO occurs. This specific phase involves a series of reactions in which there are a variety of enzymes required to ensure proper regulation. This phase is characterized by the conversion of G3P, which was produced in earlier phase, back to ribulose 1,5-bisphosphate. This process requires ATP and specific enzymes. The enzymes involved in this process include: triose phosphate isomerase, aldolase, fructose-1,6-bisphosphatase, transketolase, sedoheptulase-1,7-bisphosphatase, phosphopentose isomerase, phosphopentose epimerase, and phosphoribulokinase. The following is a brief summary of each enzyme and its role in the regeneration of ribulose 1,5-bisphosphate in the order it appears in this specific phase.

1) Triose phosphate isomerase: converts all G3P molecules into DHAP

2) Aldolase and fructose-1,6-bisphosphatase: converts G3P and DHAP into fructose 6-phosphate

3) Transketolase: removes two carbon molecules in fructose 6-phosphate to produce erythrose 4-phosphate (E4P); the two removed carbons are added to G3P to produce xylulose-5-phosphate (Xu5P)

4) Aldolase: converts E4P and a DHAP to sedoheptulose-1,7-bisphosphate

5) Sedoheptulase-1,7-bisphosphatase: cleaves the sedohetpulose-1,7-bisphosphate into sedoheptulase-7-phosphate (S7P)

6) Transketolase: removes two carbons from S7P and two carbons are transferred to one of the G3P molecules producing ribose-5-phosphate (R5P)and another Xu5P

7) Phosphopentose isomerase: converts the R5P into ribulose-5-phosphate (Ru5P)

8) Phosphopentose epimerase: converts the Xu5P into Ru5P

9) Phosphoribulokinase: phosphorylates Ru5P into ribulose-1,5-bisphosphate

After this final enzyme performs this conversion, the Calvin cycle is considered complete. The regulation of the Calvin cycle requires many key enzymes to ensure proper carbon fixation.

The Reverse TCA Cycle

The reverse TCA cycle utilizes carbon dioxide and water to form carbon compounds.

Learning Objectives

List the enzymes and function that are unique to the reverse TCA cycle (ATP citrate lyase; 2-oxoglutarate:ferredoxin oxidoreductase; pyruvate:ferredoxin oxidoreductase)

Key Takeaways

Key Points

  • The TCA cycle utilizes complex carbon molecules and oxidizes them to carbon dioxide and water.
  • The reverse TCA utilizes carbon dioxide and water to produce carbon molecules.
  • There are three major enzymes that are unique to reverse TCA including ATP citrate lyase which converts citrate into oxaloacetate and acetyl CoA.

Key Terms

  • Krebs cycle: A series of enzymatic reactions that occurs in all aerobic organisms; it involves the oxidative metabolism of acetyl units and serves as the main source of cellular energy.
  • ATP citrate lyase: ATP citrate lyase is an enzyme that represents an important step in fatty acid biosynthesis. This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates (which causes energy) and the production of fatty acids.
  • carboxylation: A reaction that introduces a carboxylic acid into a molecule.


The Reverse Citric Acid Cycle: An overview of the reverse citric acid cycle.

The citric acid cycle (TCA) or Krebs cycle, is a process utilized by numerous organisms to generate energy via the oxidation of acetate derived from carbohydrates, fats, and proteins into carbon dioxide. The cycle plays a critical role in the maintenance of numerous central metabolic processes. However, there are numerous organisms that undergo reverse TCA or reverse Krebs cycles. This process is characterized by the production of carbon compounds from carbon dioxide and water. The chemical reactions that occur are the reverse of what is seen in the TCA cycle. There are numerous anaerobic organisms that utilize a cyclic reverse TCA cycle and an example includes organisms classified as Thermoproteus. The following is a brief overview of the reverse TCA cycle.

Reverse TCA Summary

The reverse TCA cycle is a series of chemical reactions by which organisms produce carbon compounds from carbon dioxide and water. The reverse TCA cycle requires electron donors and often times, bacteria will use hydrogen, sulfide or thiosulfate for this purpose. The reverse TCA is considered to be an alternative to photosynthesis which produces organic molecules as well. Reverse TCA, a form of carbon fixation, utilizes numerous ATP molecules, hydrogen and carbon dioxide to generate an acetyl CoA. This process requires a number of reduction reactions using various carbon compounds. The enzymes, unique to reverse TCA, that function in catalyzing these reactions include: ATP citrate lyase, 2-oxoglutarate:ferredoxin oxidoreductase, and pyruvate:ferredoxin oxidoreductase. ATP citrate lyase is one of the key enzymes that function in reverse TCA. ATP citrate lyase is the enzyme responsible for cleaving citrate into oxaloacetate and acetyl CoA. These enzymes are unique to reverse TCA and are necessary for the reductive carboxylation to occur.

In reverse TCA, the following occurs in a cyclic manner:

1) oxaloacetate is converted to malate (NADH/H+ is utilized and NAD+ is produced)

2) malate is converted to fumarate (H20 molecule is produced)

3) fumarate is converted to succinate via a fumarate-reductase enzyme (FADH2 is converted to FAD)

4) succinate is converted to succinyl-CoA (ATP is hydrolyzed to ADP+Pi)

5) succincyl CoA is converted to alpha-ketoglutarate via an alpha-ketoglutarate synthase (reduction of carbon dioxide occurs and oxidation of coenzyme A)

6) alpha-ketoglutarate is converted to isocitrate (NAD(P)H/H+ and CO2 is broken down to NAD(P+)

7) isocitrate is converted to citrate

8) ATP citrate lyase is then used to convert citrate to oxaloacetate and acetyl CoA (ATP is hydrolyzed to ADP and Pi).

9) Pathway is cyclic and continues cycle from step 1

An example of a microorganism that utilizes reverse TCA includes Thermoproteus. Thermoproteusis type of prokaryotic that is characterized as a hydrogen-sulfur autotroph. The organisms classified as Thermoproteus utilizes sulfur reduction for metabolic processes. As previously mentioned, organisms that use reverse TCA may use sulfur as an electron donor to carry out this metabolic process.

The Acetyl-CoA Pathway

The acetyl-CoA pathway utilizes carbon dioxide as a carbon source and often times, hydrogen as an electron donor to produce acetyl-CoA.

Learning Objectives

Describe the role of the carbon monoxide dehydrogenase and acetyl-CoA synthetase in the acetyl-CoA pathway

Key Takeaways

Key Points

  • The acetyl-CoA pathway utilizes two major enzymes in the production of acetyl-CoA: carbon monoxide dehydrogenase and acetyl-CoA synthase.
  • Carbon monoxide dehydrogenase functions in the reduction of carbon dioxide to a methyl group.
  • Acetyl-CoA synthase functions in combining carbon monoxide and a methyl group to produce acetyl-CoA.

Key Terms

  • acetogenesis: The anaerobic production of acetic acid or acetate by bacteria.

The acetyl coenzyme A (CoA) pathway, commonly referred to as the Wood-Ljungdahl pathway or the reductive acetyl-CoA pathway, is one of the major metabolic pathways utilized by bacteria. This specific pathway is characterized by the use of hydrogen as an electron donor and carbon dioxide as an electron acceptor to produce acetyl-CoA as the final product. Acetyl-CoA is a major component in numerous metabolic processes as it plays a key role in the citric acid cycle. The main function of acetyl-CoA in the citric cycle is to transport carbon atoms. In regards to molecular structure, acetyl-CoA functions as the thioester between conezyme A and acetic acid. Specific types of organisms that utilize this pathway include archaea classified as methanogens and acetate-producing bacteria as well. The following is a brief overview of the acetyl-CoA pathway..


Acetyl-CoA Pathway: An overview of the acetyl-CoA pathway

The acetyl-CoA pathway begins with the reduction of a carbon dioxide to carbon monoxide. The other carbon dioxide is reduced to a carbonyl group. The two major enzymes involved in these processes are carbon monoxide dehydrogenase and acetyl CoA synthase complex. The carbon dioxide that is reduced to a carbonyl group, via the carbon monoxide dehydrogenase, is combined with the methyl group to form acetyl-CoA. The acetyl-CoA synthase complex is responsible for this reaction.

Carbon Monoxide Dehydrogenase

Carbon monoxide dehydrogenase, the enzyme responsible for the reduction of a carbon dioxide to a carbonyl group, functions in numerous biochemical processes. These processes include metabolism of methanogens, acetogenic and sulfate-reducing bacteria. Specifically, the acetyl-CoA pathway is utilized by bacteria that are classified as methanogens and acetate-producing organisms. The carbon monoxide dehydrogenase allows organisms to use carbon dioxide as a source of carbon and carbon monoxide as a source of energy.The carbon monoxide dehydrogenase can also form a complex with the acetyl-CoA synthase complex which is key in the acetyl-CoA pathway.

Acetyl-CoA Synthetase

Acetyl-CoA synthetase is a class of enzymes that is key to the acetyl-CoA pathway. The acetyl-CoA synthetase functions in combining the carbon monoxide and a methyl group to produce acetyl-CoA..


Acetyl-CoA Structure: Schematic of the structure of acetyl-CoA

Microorganisms and the Acetyl-CoA Pathway

The ability to utilize the acetyl-CoA pathway is advantageous due to the ability to utilize both hydrogen and carbon dioxide to produce acetyl-CoA. Specific types of bacteria which utilize the acetyl-CoA pathway include methanogens and acetate-producing bacteria.


Methanogens are types of organisms, classified as archaea, that exhibit the ability to produce methane as a metabolic byproduct. Methanogens, which are found in numerous environments including wetlands, marine sediments, hot springs and hydrothermal vents, are able to use carbon dioxide as a source of carbon for growth. In addition, the carbon dioxide is used as an electron acceptor in the production of methane. Methanogens are able to utilize the acetyl-CoA pathway to fix carbon dioxide.


Acetate producing bacteria, or acetogens, are a class of microorganisms that are able to generate acetate as a product of anaerobic respiration. This process, known as acetogenesis, will occur in organisms that are typically found in anaerobic environments. Acetogens are able to use carbon dioxide as a source of carbon and hydrogen as a source of energy.

The 3-Hydroxypropionate Cycle

The 3-hydroxypropionate cycle is a carbon fixation pathway that results in the production of acetyl-CoA and glyoxylate.

Learning Objectives

Recall the two major phases and known steps in the 3-hydroxypropionate cycle

Key Takeaways

Key Points

  • The 3-hydroxypropionate cycle is a newly identified pathway and many of the exact details which occur are currently under investigation.
  • This pathway is utilized in green non sulfur bacteria such as Chloroflexus aurantiacus.
  • The pathway can be divided into major phases which includes carbon dioxide fixation and gloxylate assimilation.

Key Terms

  • glyoxylate: a salt or ester of glyoxylic acid
  • carboxylation: A reaction that introduces a carboxylic acid into a molecule.

Carbon fixation is a key pathway in numerous microorganisms, resulting in the formation of organic compounds deemed necessary for cellular processes. One of the pathways that is utilized for carbon fixation is the 3-hydroxypropionate cycle. Specifically, in this cycle, the carbon dioxide is fixed by acetyl-CoA and propionyl-CoA carboxylases. This process results in the formation of malyl-CoA which is further split into acetyl-CoA and glyoxylate. Propionyl-CoA carboxylase is an enzyme that functions in the carboxylation of propionyl CoA. This enzyme functions in the mitochondrial matrix and is biotin dependent. The acetyl-CoA carboxylase utilized in this cycle is biotin-dependent as well and catalyzes the carboxylation of acetyl-CoA to malonyl-CoA.

This pathway produces pyruvate via conversion of bicarbonate and also results in the production of intermediates such as acetyl-CoA, gloxylate and succinyl-CoA. To date, this pathway has been identified in organisms classified as green non sulfur bacteria, specifically Chloroflexus aurantiacus () and in chemotrophic archaea. The green non sulfur bacteria uses reduced sulfur compounds, such as hydrogen sulfide or thiosulfate as an electron donor for metabolism. The ability of Chloroflexus aurantiacus to utilize this pathway is unique. The 3-hydroxypropionate cycle is a newly discovered pathway, thus, the exact details involving this process in regards to enzymes and intracellular components are still currently under investigation. However, the cycle can be broken down into two major phases, carbon dioxide fixation and glyoxylate assimilation. Glyoxylate, the conjugate base of glyoxylic acid, is the form that exists at a neutral pH. The importance of glyoxylate within microorganisms is in its ability to convert fatty acids into carbohydrates. Numerous types of organisms including bacteria, fungi and plants can utilize glyoxylate for these processes.


Chloroflexus aurantiacus: An image of Chloroflexus aurantiacus, a green nonsulfur bacteria that utilizes the 3-hydroxypropionate pathway.

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