Lipoyl synthase is an

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. A ...

that belongs to the

radical SAM Radical SAM is a designation for a superfamily of enzymes that use a +_cluster.html" ;"title="Fe-4Ssup>+ cluster">Fe-4Ssup>+ cluster to reductively cleave ''S''-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radi ...

( ''S''-adenosyl methionine) family. Within the radical SAM superfamily, lipoyl synthase is in a sub-family of enzymes that catalyze sulfur insertion reactions. Enzymes in this family contain two 4Fe-4S clusters, from which they obtain the sulfur groups that will be transferred onto the corresponding substrates. This particular enzyme participates in

lipoic acid Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is a ...

metabolism, so it transfers two

sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

atoms from its 4Fe-4S cluster onto the protein N₆-(octanoyl)lysine through

radical Radical may refer to: Politics and ideology Politics *Radical politics, the political intent of fundamental societal change *Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...

generation. This enzyme is usually localized to the

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

. Two organisms that have been extensively studied with regards to this enzyme are ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' and ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

.'' It is also found in other organisms, such as yeast and plants.

Nomenclature

The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

of this enzyme class is protein N6-(octanoyl)lysine:sulfur sulfurtransferase. Other names in common use include: * LS, * LipA, * lipoate synthase, and * protein 6-N-(octanoyl)lysine:sulfur sulfurtransferase.

Mechanism of lipoyl synthase

Lipoyl synthase uses two sulfurs from one of its two Fe-4Sclusters and attaches them to the 6th and 8th carbon of the protein N6-(octanoyl)lysine substrate, to convert it into protein N6-(lipoyl)lysine. The other Fe-4Scluster is coordinated by the radical SAM motif of the enzyme (CxxxCxxC) and participates in radical SAM characteristic chemistry to activate the substrate for subsequent sulfur insertion. Below is the overall reaction for this enzyme: :protein N6-(octanoyl)lysine + 2 sulfur + 2 S-adenosyl-L-methionine <=> protein N6-(lipoyl)lysine + 2 L-methionine + 2 5'-deoxyadenosine All in all, the 3 substrates of this enzyme are protein N6-(octanoyl)lysine,

, and

S-adenosyl-L-methionine ''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...

, whereas its 3

products Product may refer to: Business * Product (business), an item that serves as a solution to a specific consumer problem. * Product (project management), a deliverable or set of deliverables that contribute to a business solution Mathematics * Produ ...

are protein N6-(lipoyl)lysine,

L-methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical rol ...

, and 5'-deoxyadenosine.

Importance of lipoyl synthase

This enzyme participates in

metabolism, where it performs the final step in lipoic acid biosynthesis. Lipoic acid is a cofactor that has different functions within different organisms. The

generation in yeast cells increases the number of divisions in the cells as well as protects yeast cells from hydrogen peroxide.

Lipoic acid Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is a ...

is an important co-factor in many enzyme systems, and one of them is the

pyruvate dehydrogenase complex Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and t ...

. Studies that repressed the function of lipoyl synthase in ''Arabidopsis thaliana'' seeds showed that this did not have adverse effects on seed growth and weight, but shortened the generation time as well as the flowering time of the plants. Repression resulted in earlier flowering times and decreased the generation times between seeds by almost 10%.

Possible side effects

Overexpression of this enzyme in sunflower plants has been found to eventually sequester the amount of SAM present in transgenic ''Arabidopsis'' plants. SAM is a molecule that is required in other enzymatic complexes found in this plant as well, as well as the overall structure of the plant, so this sequestration may cause a reduction in the fatty acid biosynthesis in the ''Arabidopsis'' seeds.

References

EC 2.8.1 Enzymes of unknown structure {{2.8-enzyme-stub