biochemistry 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 ...

, a metabolon is a temporary structural-functional complex formed between sequential

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

s of a

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical rea ...

, held together both by

non-covalent interaction In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The c ...

s and by structural elements of the cell, such as

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a signif ...

s and proteins of the cytoskeleton. The formation of metabolons allows the intermediate product from one enzyme to be passed (channelling) directly into the active site of the next consecutive enzyme of the metabolic pathway. 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 ...

is an example of a metabolon that facilitates substrate channeling. Another example is the dhurrin synthesis pathway in sorghum, in which the enzymes assemble as a metabolon in lipid membranes. During the functioning of metabolons, the amount of water needed to hydrate the enzymes is reduced and enzyme activity is increased.

History

The concept of structural-metabolic cellular complexes was first conceived in 1970 by A. M. Kuzin of the USSR Academy of Sciences, and adopted in 1972 by Paul A. Srere of the

University of Texas The University of Texas at Austin (UT Austin, UT, or Texas) is a public research university in Austin, Texas. It was founded in 1883 and is the oldest institution in the University of Texas System. With 40,916 undergraduate students, 11,075 ...

for the enzymes of the

. This hypothesis was well accepted in the former USSR and further developed for the complex of

glycolytic 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) ...

enzymes (Embden-Meyerhof-Parnas pathway) by B.I. Kurganov and A.E. Lyubarev. In the mid-1970s, the group of F.M. Clarke at the

University of Queensland , mottoeng = By means of knowledge and hard work , established = , endowment = A$224.3 million , budget = A$2.1 billion , type = Public research university , chancellor = Peter Varghese , vice_chancellor = Deborah Terry , city = B ...

, Australia also worked on the concept. The name “metabolon” was first proposed in 1985 by Paul Srere during a lecture in Debrecen, Hungary.Robinson, J. B., Jr. & Srere, P. A. (1986) Interactions of sequential metabolic enzymes of the mitochondria: a role in metabolic regulation, pp. 159–171 in Dynamics of Biochemical Systems (ed. Damjanovich, S., Keleti, T. & Trón, L.), Akadémiai Kiadó, Budapest, Hungary

The case of Fatty Acid Synthesis

In '' Chaetomium thermophilum'', a complex of a metabolon exists between fatty acid synthase and a MDa carboxylase, and was observed using chemical cross-linking coupled to

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...

and visualized by

cryo-electron microscopy Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample sol ...

. The Fatty acid synthesis metabolon in ''C. thermophilum'' is highly flexible, and although a high-resolution structure of

Fatty acid synthase Fatty acid synthase (FAS) is an enzyme that in humans is encoded by the ''FASN'' gene. Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis. It is not a single enzyme but a whole enzymatic system composed of two ide ...

was possible, the metabolon was highly flexible, hindering high-resolution structure determination.

Examples

References

{{reflist Metabolism Protein complexes

History

The case of Fatty Acid Synthesis

Examples

See also

References