The term amphibolic ( grc, ἀμφίβολος, translit=amphibolos, lit=ambiguous, struck on both sides) is used to describe a

biochemical Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

pathway that involves both

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...

and

anabolism Anabolism () is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-do ...

. Catabolism is a degradative phase of metabolism in which large molecules are converted into smaller and simpler molecules, which involves two types of reactions. First, hydrolysis reactions, in which catabolism is the breaking apart of molecules into smaller molecules to release energy. Examples of catabolic reactions are digestion and cellular respiration, where sugars and fats are broken down for energy. Breaking down a protein into

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s, or a triglyceride into fatty acids, or a disaccharide into

monosaccharide Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. They are usually colorless, water-solu ...

s are all hydrolysis or catabolic reactions. Second, oxidation reactions involve the removal of hydrogens and electrons from an organic molecule. Anabolism is the biosynthesis phase of metabolism in which smaller simple precursors are converted to large and complex molecules of the cell. Anabolism has two classes of reactions. The first are dehydration synthesis reactions; these involve the joining of smaller molecules together to form larger, more complex molecules. These include the formation of carbohydrates, proteins, lipids and nucleic acids. The second are reduction reactions, in which hydrogens and electrons are added to a molecule. Whenever that is done, molecules gain energy. The term amphibolic was proposed by B. Davis in 1961 to emphasise the dual metabolic role of such pathways. These pathways are considered to be central metabolic pathways which provide, from catabolic sequences, the intermediates which form the substrate of the metabolic processes.

Reactions exist as amphibolic pathway

All the reactions associated with synthesis of biomolecule converge into the following pathway, viz.,

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) ...

, the Krebs cycle and the electron transport chain, exist as an amphibolic pathway, meaning that they can function anabolically as well as catabolically. Other important amphibolic pathways are the Embden-Meyerhof pathway, the

pentose phosphate pathway The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...

and the

Entner–Doudoroff pathway The Entner–Doudoroff pathway (ED Pathway) is a metabolic pathway that is most notable in Gram-negative bacteria, certain Gram-positive bacteria and archaea. Glucose is the substrate in the ED pathway and through a series of enzyme assisted che ...

Embden-Meyerhoff

The Embeden–Meyerhof pathway and the Krebs cycle are the centre of metabolism in nearly all bacteria and eukaryotes. They provide not only energy but also

precursors Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of unr ...

for biosynthesis of macromolecules that make up living systems.

Citric acid cycle

The

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protei ...

(Krebs cycle) is a good example of an amphibolic pathway because it functions in both the degradative (carbohydrate, protein, and fatty acid) and biosynthetic processes. The citric acid cycle occurs on the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrio ...

of bacteria and within the mitochondria of eukaryotic cells. It provides electrons to the electron transport chain which is used to drive the production of ATP in oxidative phosphorylation. Intermediates in the citric acid cycle, such as oxaloacetate, are used to synthesize macromolecule constituents such as amino acids, e.g. glutamate and aspartate. The first reaction of the cycle, in which oxaloacetate (a four-carbon compound) condenses with acetate (a two-carbon compound) to form citrate (a six-carbon compound) is typically anabolic. The next few reactions, which are intramolecular rearrangements, produce

isocitrate Isocitric acid is a structural isomer of citric acid. Since citric acid and isocitric acid are structural isomers, they share similar physical and chemical properties. Due to these similar properties, it is difficult to separate the isomers. Salts ...

. The following two reactions, namely the conversion of D-

to α-Ketoglutarate followed by its conversion to

succinyl-CoA Succinyl-coenzyme A, abbreviated as succinyl-CoA () or SucCoA, is a thioester of succinic acid and coenzyme A. Sources It is an important intermediate in the citric acid cycle, where it is synthesized from α-ketoglutarate by α-ketoglutarate de ...

, are typically catabolic. Carbon dioxide is lost in each step and succinate (a four-carbon compound) is produced. There is an interesting and critical difference in the coenzymes used in catabolic and anabolic pathways; in catabolism NAD+ serves as an oxidizing agent when it is reduced to NADH. Whereas in anabolism the coenzyme NADPH serves as the reducing agent and is converted to its oxidized form NADP⁺. Citric acid cycle has two modes that play two roles, the first being energy production produced by the oxidative mode, as the acetyl group of acetyl-coA is fully oxidized to CO₂. This produces most of the ATP in the metabolism of aerobic heterotrophic metabolism, as this energy conversion in the membrane structure (cytoplasmic membrane in bacteria and mitochondria in eukaryotes) by oxidative phosphorylation by moving electron from donor (NADH and FADH₂) to the acceptor O₂. Every cycle give 3 NADH, 1 FADH₂, CO₂ and GTP. The second role is biosynthetic, as citric acid cycle regenerate oxaloacetate when cycle intermediates are removed for biosynthesis. File:Citric acid cycle with aconitate 2.svg, Figure 1: Citric acid cycle

Pentose phosphate pathway

The pentose phosphate pathway gets its name because it involves several intermediates that are phosphorylated five-carbon sugars (

pentose In chemistry, a pentose is a monosaccharide (simple sugar) with five carbon atoms. The chemical formula of many pentoses is , and their molecular weight is 150.13 g/mol.monomers for many metabolic pathways by transforming glucose into the four-carbon sugar

erythrose Erythrose is a tetrose saccharide with the chemical formula C4H8O4. It has one aldehyde group, and is thus part of the aldose family. The natural isomer is D-erythrose; it is a diastereomer of D -threose. Erythrose was first isolated in 1849 ...

and the five-carbon sugar ribose; these are important monomers in many metabolic pathways. Many of the reactants in this pathway are similar to those in glycolysis, and both occur in

. The ribose-5-phosphate can be transported into the nucleic acid metabolism, producing the basis of DNA and RNA monomers, the nucleotides. In

meristematic The meristem is a type of tissue found in plants. It consists of undifferentiated cells (meristematic cells) capable of cell division. Cells in the meristem can develop into all the other tissues and organs that occur in plants. These cells conti ...

cells, large amounts of DNA must be produced during the

S-phase S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...

of a short cell cycle; this pathway is an extremely important part of the metabolism of these cells. In these cells, the pentose phosphate pathway is active and shifted in favor of ribose production.

Entner-Doudoroff pathway

The Entner-Doudoroff pathway is a glycolytic pathway that is considered the second pathway used for carbohydrates used by certain microbes. In this process, glucose-6-phosphate is oxidized through 6-phosphogluconate to pyruvate and glyceraldehyde 3-phosphate, with the concomitant reduction of NADP. By conventional glyceraldehyde-3-phosphate oxidation to pyruvate, one NAD is reduced and a net one ATP is formed. In that pathway, for every glucose molecule there is an "investment" of one ATP molecule and a yield of two ATP and two pyruvate molecules and one NADH. The difference between the glycolytic used by humans and this pathway is that the latter requires one ATP to yield two ATP and two pyruvates as a net of only one NADPH produced and one ATP result (from

substrate-level phosphorylation Substrate-level phosphorylation is a metabolism reaction that results in the production of ATP or GTP by the transfer of a phosphate group from a substrate directly to ADP or GDP. Transferring from a higher energy (whether phosphate group att ...

), and the former requires two ATP molecules to yield four ATP and two pyruvate molecules per glucose as a net of two ATP molecules. File:Entner–Doudoroff pathway.svg, Figure 2: Entner- Doudoroff pathway

Regulation

The cell determines whether the amphibolic pathway will function as an anabolic or catabolic pathway by enzyme–mediated regulation at a

transcriptional Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...

and post-transcriptional level. As many reactions in amphibolic pathways are freely reversible or can be bypassed, irreversible steps that facilitate their dual function are necessary. The pathway uses a different enzyme for each direction for the irreversible step in the pathway, allowing independent regulation of catabolism and anabolism. Due their inherent duality, amphibolic pathways represent the regulation modes of both anabolic by its

negative feedback Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...

end product and catabolic by feedback by energy indicator sequences.

References

{{Reflist Metabolism