Pathways

Sarcosine is a compound derived from the amino acid glycine and is involved in both its synthesis and degradation, and is an intermediate in the metabolism of choline to glycine. In cases of prostate cancer, the cancer cells seem to produce higher levels of sarcosine. Elevated levels of sarcosine found in the urine of patients with prostate cancer, and it has been suggested that these elevated levels are responsible for the development of the cancer. This pathway begins with choline’s transport into the mitochondrial matrix via xolute carrier family protein 44 A1 and the choline transporter-like protein 2. Once in the matrix, choline is oxidized to betaine aldehyde by choline dehydrogenase, and in the process reduces an acceptor. Betaine aldehyde is then converted to betaine by the addition of a water molecule by alpha-aminoadipic semialdehyde dehydrogenase. Following this, betaine is transported out of the mitochondria by an unknown transporter, where it then reacts with homocysteine to form dimethylglycine and L-methionine in a reaction catalyzed by betaine-homocysteine S-methyltransferase 1. The dimethylglycine is then transported back into the mitochondrial matrix by another unknown transporter, where it can react with tetrahydrofolate to form sarcosine and 5-methyltetrahydrofolic acid in a reaction catalyzed by dimethylglycine dehydrogenase. In at least some cases of prostate cancer cells, the SARDH gene is mutated, which encodes the sarcosine dehydrogenase protein. This can lead to an increase of sarcosine in the cells, as sarcosine dehydrogenase typically converts sarcosine to glycine, which is then converted to and from L-serine by serine hydroxymethyltransferase. With a non-functional or less functional enzyme, sarcosine levels will be increased, and serine and glycine levels will be reduced. A separate set of reactions outside of the mitochondria begins with the L-methionine produced by betaine—homocysteine S-methyltransferase 1, which is then converted to S-adenosylmethionine by a complex consisting of S-adenosylmethionine synthase and methionine adenosyltransferase. S-adenosylmethionine then reacts with glycine reversibly to form S-adenosylhomocysteine, as well as sarcosine. The expression of the gene encoding glycine N-methyltransferase, GNMT, can also be elevated in cancer tissues, leading to an increased concentration of sarcosine outside of the mitochondria as well.

Sarcosine is a compound derived from the amino acid glycine and is involved in both its synthesis and degradation, and is an intermediate in the metabolism of choline to glycine. In cases of prostate cancer, the cancer cells seem to produce higher levels of sarcosine. Elevated levels of sarcosine found in the urine of patients with prostate cancer, and it has been suggested that these elevated levels are responsible for the development of the cancer. This pathway begins with choline’s transport into the mitochondrial matrix via xolute carrier family protein 44 A1 and the choline transporter-like protein 2. Once in the matrix, choline is oxidized to betaine aldehyde by choline dehydrogenase, and in the process reduces an acceptor. Betaine aldehyde is then converted to betaine by the addition of a water molecule by alpha-aminoadipic semialdehyde dehydrogenase. Following this, betaine is transported out of the mitochondria by an unknown transporter, where it then reacts with homocysteine to form dimethylglycine and L-methionine in a reaction catalyzed by betaine-homocysteine S-methyltransferase 1. The dimethylglycine is then transported back into the mitochondrial matrix by another unknown transporter, where it can react with tetrahydrofolate to form sarcosine and 5-methyltetrahydrofolic acid in a reaction catalyzed by dimethylglycine dehydrogenase. In at least some cases of prostate cancer cells, the SARDH gene is mutated, which encodes the sarcosine dehydrogenase protein. This can lead to an increase of sarcosine in the cells, as sarcosine dehydrogenase typically converts sarcosine to glycine, which is then converted to and from L-serine by serine hydroxymethyltransferase. With a non-functional or less functional enzyme, sarcosine levels will be increased, and serine and glycine levels will be reduced. A separate set of reactions outside of the mitochondria begins with the L-methionine produced by betaine—homocysteine S-methyltransferase 1, which is then converted to S-adenosylmethionine by a complex consisting of S-adenosylmethionine synthase and methionine adenosyltransferase. S-adenosylmethionine then reacts with glycine reversibly to form S-adenosylhomocysteine, as well as sarcosine. The expression of the gene encoding glycine N-methyltransferase, GNMT, can also be elevated in cancer tissues, leading to an increased concentration of sarcosine outside of the mitochondria as well.

Sarcosine is a compound derived from the amino acid glycine and is involved in both its synthesis and degradation, and is an intermediate in the metabolism of choline to glycine. In cases of prostate cancer, the cancer cells seem to produce higher levels of sarcosine. Elevated levels of sarcosine found in the urine of patients with prostate cancer, and it has been suggested that these elevated levels are responsible for the development of the cancer. This pathway begins with choline’s transport into the mitochondrial matrix via xolute carrier family protein 44 A1 and the choline transporter-like protein 2. Once in the matrix, choline is oxidized to betaine aldehyde by choline dehydrogenase, and in the process reduces an acceptor. Betaine aldehyde is then converted to betaine by the addition of a water molecule by alpha-aminoadipic semialdehyde dehydrogenase. Following this, betaine is transported out of the mitochondria by an unknown transporter, where it then reacts with homocysteine to form dimethylglycine and L-methionine in a reaction catalyzed by betaine-homocysteine S-methyltransferase 1. The dimethylglycine is then transported back into the mitochondrial matrix by another unknown transporter, where it can react with tetrahydrofolate to form sarcosine and 5-methyltetrahydrofolic acid in a reaction catalyzed by dimethylglycine dehydrogenase. In at least some cases of prostate cancer cells, the SARDH gene is mutated, which encodes the sarcosine dehydrogenase protein. This can lead to an increase of sarcosine in the cells, as sarcosine dehydrogenase typically converts sarcosine to glycine, which is then converted to and from L-serine by serine hydroxymethyltransferase. With a non-functional or less functional enzyme, sarcosine levels will be increased, and serine and glycine levels will be reduced. A separate set of reactions outside of the mitochondria begins with the L-methionine produced by betaine—homocysteine S-methyltransferase 1, which is then converted to S-adenosylmethionine by a complex consisting of S-adenosylmethionine synthase and methionine adenosyltransferase. S-adenosylmethionine then reacts with glycine reversibly to form S-adenosylhomocysteine, as well as sarcosine. The expression of the gene encoding glycine N-methyltransferase, GNMT, can also be elevated in cancer tissues, leading to an increased concentration of sarcosine outside of the mitochondria as well.

Sarcosinemia (SAR), also known as hypersarcosinemia, sarcosine dehydrogenase complex deficiency, SARDH deficiency, SARDHD or SARD deficiency, is an autosomal recessive metabolic disorder leading to increased levels of the amino acid sarcosine in blood plasma, as well as increased levels of sarcosine excreted in urine. SAR can be caused by a mutation, either homozygous or compound heterozygous, in the SARDH gene which codes for the sarcosine dehydrogenase enzyme. This enzyme converts sarcosine to glycine, and its absence leads to an increase in the amount of sarcosine in the body. It can also potentially be caused by a lack of folate, as folate is used in the sarcosine dehydrogenase reaction, and even with a working enzyme, the lack of substrates can prevent the conversion from occurring, leading to the same effects. The condition has been associated with mental and motor retardation, visual impairment, however other cases have been detected with no mental or physical abnormalities other than increased sarcosine levels, so it is possible that the defect is benign, or that there exist some phenotypes that are more severe than others, or unknown disorders present in the cases showing symptoms. Sarcosine can be formed from a series of reactions starting with trimethylglycine. This, along with homocysteine, react using betaine-homocysteine S-methyltransferase to form L-methionine, as well as dimethylglycine. The dimethylglycine then enters the mitochondrial matrix, and interacts with dimethylglycine dehydrogenase along with a water molecule, forming formadehyde and sarcosine. Sarcosine can also be formed in a reversible reaction from S-adenosylmethionine and glycine, using glycine N-methyltransferase as the enzyme, and forming S-adenosylhomocysteine as another product. Normally, sarcosine can interact with sarcosine dehydrogenase in the mitochondria, forming both formaldehyde and glycine. However, in this disorder, the gene encoding sarcosine dehydrogenase has been mutated and the protein is not produced, preventing this reaction from occurring. This leads to an increased concentration of sarcosine, which leads to the effects of the condition.

Sarcosinemia (SAR), also known as hypersarcosinemia, sarcosine dehydrogenase complex deficiency, SARDH deficiency, SARDHD or SARD deficiency, is an autosomal recessive metabolic disorder leading to increased levels of the amino acid sarcosine in blood plasma, as well as increased levels of sarcosine excreted in urine. SAR can be caused by a mutation, either homozygous or compound heterozygous, in the SARDH gene which codes for the sarcosine dehydrogenase enzyme. This enzyme converts sarcosine to glycine, and its absence leads to an increase in the amount of sarcosine in the body. It can also potentially be caused by a lack of folate, as folate is used in the sarcosine dehydrogenase reaction, and even with a working enzyme, the lack of substrates can prevent the conversion from occurring, leading to the same effects. The condition has been associated with mental and motor retardation, visual impairment, however other cases have been detected with no mental or physical abnormalities other than increased sarcosine levels, so it is possible that the defect is benign, or that there exist some phenotypes that are more severe than others, or unknown disorders present in the cases showing symptoms. Sarcosine can be formed from a series of reactions starting with trimethylglycine. This, along with homocysteine, react using betaine-homocysteine S-methyltransferase to form L-methionine, as well as dimethylglycine. The dimethylglycine then enters the mitochondrial matrix, and interacts with dimethylglycine dehydrogenase along with a water molecule, forming formadehyde and sarcosine. Sarcosine can also be formed in a reversible reaction from S-adenosylmethionine and glycine, using glycine N-methyltransferase as the enzyme, and forming S-adenosylhomocysteine as another product. Normally, sarcosine can interact with sarcosine dehydrogenase in the mitochondria, forming both formaldehyde and glycine. However, in this disorder, the gene encoding sarcosine dehydrogenase has been mutated and the protein is not produced, preventing this reaction from occurring. This leads to an increased concentration of sarcosine, which leads to the effects of the condition.

Sarcosinemia (SAR), also known as hypersarcosinemia, sarcosine dehydrogenase complex deficiency, SARDH deficiency, SARDHD or SARD deficiency, is an autosomal recessive metabolic disorder leading to increased levels of the amino acid sarcosine in blood plasma, as well as increased levels of sarcosine excreted in urine. SAR can be caused by a mutation, either homozygous or compound heterozygous, in the SARDH gene which codes for the sarcosine dehydrogenase enzyme. This enzyme converts sarcosine to glycine, and its absence leads to an increase in the amount of sarcosine in the body. It can also potentially be caused by a lack of folate, as folate is used in the sarcosine dehydrogenase reaction, and even with a working enzyme, the lack of substrates can prevent the conversion from occurring, leading to the same effects. The condition has been associated with mental and motor retardation, visual impairment, however other cases have been detected with no mental or physical abnormalities other than increased sarcosine levels, so it is possible that the defect is benign, or that there exist some phenotypes that are more severe than others, or unknown disorders present in the cases showing symptoms. Sarcosine can be formed from a series of reactions starting with trimethylglycine. This, along with homocysteine, react using betaine-homocysteine S-methyltransferase to form L-methionine, as well as dimethylglycine. The dimethylglycine then enters the mitochondrial matrix, and interacts with dimethylglycine dehydrogenase along with a water molecule, forming formadehyde and sarcosine. Sarcosine can also be formed in a reversible reaction from S-adenosylmethionine and glycine, using glycine N-methyltransferase as the enzyme, and forming S-adenosylhomocysteine as another product. Normally, sarcosine can interact with sarcosine dehydrogenase in the mitochondria, forming both formaldehyde and glycine. However, in this disorder, the gene encoding sarcosine dehydrogenase has been mutated and the protein is not produced, preventing this reaction from occurring. This leads to an increased concentration of sarcosine, which leads to the effects of the condition.

Sarcosinemia (SAR), also known as hypersarcosinemia, sarcosine dehydrogenase complex deficiency, SARDH deficiency, SARDHD or SARD deficiency, is an autosomal recessive metabolic disorder leading to increased levels of the amino acid sarcosine in blood plasma, as well as increased levels of sarcosine excreted in urine. SAR can be caused by a mutation, either homozygous or compound heterozygous, in the SARDH gene which codes for the sarcosine dehydrogenase enzyme. This enzyme converts sarcosine to glycine, and its absence leads to an increase in the amount of sarcosine in the body. It can also potentially be caused by a lack of folate, as folate is used in the sarcosine dehydrogenase reaction, and even with a working enzyme, the lack of substrates can prevent the conversion from occurring, leading to the same effects. The condition has been associated with mental and motor retardation, visual impairment, however other cases have been detected with no mental or physical abnormalities other than increased sarcosine levels, so it is possible that the defect is benign, or that there exist some phenotypes that are more severe than others, or unknown disorders present in the cases showing symptoms. Sarcosine can be formed from a series of reactions starting with trimethylglycine. This, along with homocysteine, react using betaine-homocysteine S-methyltransferase to form L-methionine, as well as dimethylglycine. The dimethylglycine then enters the mitochondrial matrix, and interacts with dimethylglycine dehydrogenase along with a water molecule, forming formadehyde and sarcosine. Sarcosine can also be formed in a reversible reaction from S-adenosylmethionine and glycine, using glycine N-methyltransferase as the enzyme, and forming S-adenosylhomocysteine as another product. Normally, sarcosine can interact with sarcosine dehydrogenase in the mitochondria, forming both formaldehyde and glycine. However, in this disorder, the gene encoding sarcosine dehydrogenase has been mutated and the protein is not produced, preventing this reaction from occurring. This leads to an increased concentration of sarcosine, which leads to the effects of the condition.

Metabolites of Sarecycline are predicted with biotransformer.