Pathways

Lipoate is an essential cofactor for key enzymes of oxidative metabolism. Mechanism of lipoate biosynthesis is similar to biotin biosynthesis. Octanoyltransferase facilitates the tranfer of octanoate moiety from octanoate-ACP to particular lysyl residues in lipoate-dependent enzymes. This process regenerates the acyl-carrier in the process, and create an octanylated domains in lipoate-dependent enzymes. Lipoyl synthase combines with S-adenosyl-L-methionine to generate an active lipoylated domain by converting the octanoyl side chain to an active lipoyl. Lipoyl synthase also split S-Adenosyl methionine (AdoMet) into 5'-deoxyadenosyl radical (later becomes 5'-deoxyadenosine by abstracting a hydrogen from a C-H bond) and L-methionine. L-methionine will undergo S-Adenosyl-L-Methionine Biosynthesis.

Lipoate is an essential cofactor for key enzymes of oxidative metabolism. Mechanism of lipoate biosynthesis is similar to biotin biosynthesis. Octanoyltransferase facilitates the tranfer of octanoate moiety from octanoate-ACP to particular lysyl residues in lipoate-dependent enzymes. This process regenerates the acyl-carrier in the process, and create an octanylated domains in lipoate-dependent enzymes. Lipoyl synthase combines with S-adenosyl-L-methionine to generate an active lipoylated domain by converting the octanoyl side chain to an active lipoyl. Lipoyl synthase also split S-Adenosyl methionine (AdoMet) into 5'-deoxyadenosyl radical (later becomes 5'-deoxyadenosine by abstracting a hydrogen from a C-H bond) and L-methionine. L-methionine will undergo S-Adenosyl-L-Methionine Biosynthesis.

Lipoate is an essential cofactor for key enzymes of oxidative metabolism. Mechanism of lipoate biosynthesis is similar to biotin biosynthesis. Octanoyltransferase facilitates the tranfer of octanoate moiety from octanoate-ACP to particular lysyl residues in lipoate-dependent enzymes. This process regenerates the acyl-carrier in the process, and create an octanylated domains in lipoate-dependent enzymes. Lipoyl synthase combines with S-adenosyl-L-methionine to generate an active lipoylated domain by converting the octanoyl side chain to an active lipoyl. Lipoyl synthase also split S-Adenosyl methionine (AdoMet) into 5'-deoxyadenosyl radical (later becomes 5'-deoxyadenosine by abstracting a hydrogen from a C-H bond) and L-methionine. L-methionine will undergo S-Adenosyl-L-Methionine Biosynthesis.

Lipoic acid is a compound derived from octanoic acid that is used as a cofactor in at least five enzyme systems, and is present in at least small amounts in most foods.However, these sources are covalently bound to other molecules, and aren't usable. Due to this, supplements of lipoic acid are synthesized chemically rather than obtained through natural sources. This pathway takes place entirely in the mitochondria, and begins with octanoyl bound to an acyl-carrier protein (ACP) from fatty acid biosynthesis. It can interact with lipoyl synthase to form lipoyl-ACP, after which it interacts with putative lipoyl transease in order to form protein N6-(lipoyl)lysine. Octanoyl-ACP can also interact with those enzymes in the opposite order, first the putative lipoyltransferase 2, forming protein N6-(octanoyl)lysine, and then lipoyl synthase to form protein N6-(lipoyl)lysine. At the same time, lipoic acid can form lipoyl-AMP after a reaction that exists in other organisms, and is likely present in Xenopus laevis, and the lipoyl-AMP can then interact with lipoyltransferase 1 to form the protein N6-(lipoyl)lysine. As all branches of the pathway produce this, it is the final and only product of this pathway.

Lipoic acid metabolism starts with caprylic acid being introduced into the cytoplasm, however, no transporter has been identified yet. i) Once caprylic acid is in the cytoplasm, it can react with a holo-acp through an ATP-driven 2-acylglycerophosphoethanolamine acyltransferase/acyl-ACP synthetase resulting in pyrophosphate, AMP, and octanoyl-[acp]. The latter compound can also be obtained from palmitate biosynthesis. ii) Octanoyl-acp then interacts with a lipoyl-carrier protein L-lysine through an octanoyltransferase resulting in a hydrogen ion, a holo-acyl-acp, and an N6-(octanoyl)lysine. iii) N6-(octanoyl)lysine reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier], and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, an L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and protein N6-(octanoyl)lysine. Caprylic acid can also interact with ATP and a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in an AMP, pyrophosphate, hydrogen ion, and protein N6-(octanoyl)lysine. The latter compound reacts with an S-adenosylmethionine, a sulfurated[sulfur carrier] and a reduced ferredoxin through a lipoate-protein ligase A, resulting in a 5-deoxyadenosine, an L-methionine, an unsulfurated [sulfur carrier], oxidized ferredoxin, and a protein N6-(octanoyl)lysine. R-Lipoic acid can be absorbed from the environment, as seen in studies by Morris TW. In this pathway, the lipoyl-protein ligase LplA utilizes pre-existing lipoate that has been imported from outside the cell, and thus catalyzes a salvage pathway. Lipoic acid interacts with ATP and hydrogen ion through a lipoyl-protein ligase A, resulting in a pyrophosphate and a lipoyl-AMP (lipoyl-adenylate). This compound then interacts with a lipoyl-carrier protein-L-lysine through a lipoate-protein ligase A resulting in an AMP, a hydrogen ion, and a protein N6-(lipoyl) lysine. It has been suggested that the conversion of octanoylated-domains into lipoylated ones described in this pathway may be a type of a repair pathway, activated only if the other lipoate biosynthetic pathways are malfunctioning.

Lipoic acid, also known as α-lipoic acid and thioctic acid, is an organosulfur (sulfur-containing) coenzyme. Lipoic acid is an essential cofactor of dehydrogenase enzymes involved in the oxidative decarboxylation of 2-oxoacids and the glycine cleavage (glycine decarboxylase) system. Lipoic acid is derived from the 8-carbon fatty acid, octanoic acid. In most eukaryotes, lipoic acid is synthesised in mitochondrion. However, in plants, the biosynthetic pathway is present in plastids in addition to mitochondria. Lipoic acid is made in animals normally, and is essential for aerobic metabolism. Lipoic acid metabolism starts by the precursor, Octanoyl-[acyl-carrier-protein], which is made via fatty acid biosynthesis. Octanoyl-[acp] can be catalyzed by either lipoyl synthase (LipA) or lipoyl(octanoyl) transferase (LipB), to produce lipoyl-[acp] or protein N6-(octanoyl)lysine respectively. Lastly, protein N6-(lipoyl)lysine is generated via synthesis of protein N6-(octanoyl)lysine by LipA, or via the transfer of a lysine group to lipoyl-[acp] by LipB.

The lipoic acid metabolism involves the metabolism of octanoyl-acp by reacting with a sulfur donor and a S-adenosylmethionine through a lipoic acid synthetase resulting in the release of L-methionine, deoxyadenosine and lipoyl-ACP. Lipoyl-ACP reacts with an apoprotein through a through a lipoyl(octanoyl) transferase resulting in the release of an ACP and a protein N6-(lypoyl)lysine. Octanoyl-acp can also interact with a apoprotein through a lipoyl(octanoyl) transferase resulting in the release of an ACP and a protein N6-(octanoyl)lysine. Protein N6-(octanoyl) lysine reacts with sulfur donor and a S-adenosylmethionine through a lipoic acid synthetase resulting in the release of L-methionine, deoxyadenosine and Protein N6(lipoyl) lysine.

Lipoic acid is a compound derived from octanoic acid that is used as a cofactor in at least five enzyme systems, and is present in at least small amounts in most foods.However, these sources are covalently bound to other molecules, and aren't usable. Due to this, supplements of lipoic acid are synthesized chemically rather than obtained through natural sources. This pathway takes place entirely in the mitochondria, and begins with octanoyl bound to an acyl-carrier protein (ACP) from fatty acid biosynthesis. It can interact with lipoyl synthase to form lipoyl-ACP, after which it interacts with putative lipoyl transease in order to form protein N6-(lipoyl)lysine. Octanoyl-ACP can also interact with those enzymes in the opposite order, first the putative lipoyltransferase 2, forming protein N6-(octanoyl)lysine, and then lipoyl synthase to form protein N6-(lipoyl)lysine. At the same time, lipoic acid can form lipoyl-AMP after a reaction that likely exists in Danio rerio but is unknown, and the lipoyl-AMP can then interact with lipoyltransferase 1 to form the protein N6-(lipoyl)lysine. As all branches of the pathway produce this, it is the final and only product of this pathway.

Lipoic acid is a compound derived from octanoic acid that is used as a cofactor in at least five enzyme systems, and is present in at least small amounts in most foods.However, these sources are covalently bound to other molecules, and aren't usable. Due to this, supplements of lipoic acid are synthesized chemically rather than obtained through natural sources. This pathway takes place entirely in the mitochondria, and begins with octanoyl bound to an acyl-carrier protein (ACP) from fatty acid biosynthesis. It can interact with lipoyl synthase to form lipoyl-ACP, after which it interacts with putative lipoyl transease in order to form protein N6-(lipoyl)lysine. Octanoyl-ACP can also interact with those enzymes in the opposite order, first the putative lipoyltransferase 2, forming protein N6-(octanoyl)lysine, and then lipoyl synthase to form protein N6-(lipoyl)lysine. At the same time, lipoic acid can interact with a lipoate protein ligase, consisting of a currently unknown protein, adding a lipoyl-carrier protein-L-lysine, also forming a protein N6-(lipoyl)lysine. Finally, lipoic acid can form lipoyl-AMP after a reaction catalyzed by the same lipoate protein ligase, which can then interact with lipoyltransferase 1 to form the protein N6-(lipoyl)lysine. This is the final and only product of this pathway.