Biosynthesis of Glycine
Glycine, serine and threonine metabolism 14
The 3-Phosphoglycerate Family of Amino Acids Includes Ser, Gly, and Cys
Serine, glycine, and cysteine are derived from the glycolytic intermediate 3-Phosphoglyceric acid (3PG). Glycine is derived from Serine. 3-Phosphoglyceric acid (3PG) is the conjugate acid of glycerate 3-phosphate (GP). The glycerate is a biochemically significant metabolic intermediate in both glycolysis and the Calvin cycle. 10
Enzymes used in Glycolysis:
Hexokinase (EC 2.7.1.1 )
Phosphoglucose isomerase (EC 5.3.1.9 )
Phosphofructokinase (EC 2.7.1.11 )
Fructose-bisphosphate aldolase (EC 4.1.2.13 )
Triosephosphate isomerase (EC 5.3.1.1 )
Glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12 )
Phosphoglycerate kinase (EC 2.7.2.3 )
Phosphoglycerate mutase (EC 5.4.2.1 )
Enolase (EC 4.2.1.11 )
Pyruvate kinase (EC 2.7.1.40 )
In all non-photosynthetic organisms, including mammals, a major source of L-serine is the phosphorylated pathway of L-serine biosynthesis. 15 The pathway consists of three enzymes,
D-3-phosphoglycerate dehydrogenase (PGDH),
phosphoserine amino transferase (PSAT), and
L-phosphoserine phosphatase (PSP).
Phosphoglycerate dehydrogenase
http://en.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase
Phosphoserine transaminase
http://en.wikipedia.org/wiki/Phosphoserine_transaminase
Phosphoserine phosphatase
http://en.wikipedia.org/wiki/Phosphoserine_phosphatase
Serine hydroxymethyltransferase
http://en.wikipedia.org/wiki/Serine_hydroxymethyltransferase
(a) Schematic of the phosphorylated pathway; names of enzymes are underlined;
PGDH, 3-phosphoglycerate dehydrogenase;
PSAT, phosphoserine aminotransferase;
PSP, phosphoserine phosphatase;
3-PHP, 3-phosphohydroxypyruvate;
3-PS, 3-phosphoserine;
L-Glu,
L-glutamate;
2-OG, 2-oxoglutarate;
Pi, inorganic phosphate.
(b) Domain architectures and effectors of PGDH; the domains of PGDH proteins from archaea [S. tokodaii (StPGDH)], bacteria [E. coli (EcPGDH) and M. tuberculosis (MtPGDH)], cyanobacterium [A. halophytica (AhPGDH)], mammals [R. norvegicus (RnPGDH) and Homo sapiens (HsPGDH)], and plant [A. thaliana (AtPGDHs)] are schematically shown with highlighted catalytic, ACT, and ASB domains. Because ACT domains of HsPGDH and RnPGDH are not functional, they are indicated in white. Numbers in parenthesis indicate references. In ref. 14, HsPGDH was not inhibited by serine, although the data were not shown (“No ? ” in the figure).
The diversion of 3-phosphoglycerate. (3PG) from glycolysis is achieved via 3-phosphoglycerate dehydrogenase. 12 ( figure below )
3-phosphoglycerate dehydrogenase (PGDH) (EC 1.1.1.95)
3-Phosphoglycerate dehydrogenase catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the committed step in the phosphorylated pathway of L-serine biosynthesis. It is also essential in cysteine and glycine synthesis.
3-Phosphoglycerate dehydrogenase (PGDH) is activated by various biomolecules and indicate that serine biosynthesis is regulated by multiple pathways. 13
Biosynthesis of serine from 3-phosphoglycerate.
This NAD+-dependent oxidation of 3-PG yields 3-phosphohydroxypyruvate—which, as an a-keto acid, is a substrate for transamination by glutamate to give 3-phosphoserine (reaction 2, above). Serine phosphatase then generates serine (Figure above, reaction 3). Serine inhibits the first enzyme, 3-PG dehydrogenase, and thereby feedback-regulates its own synthesis. Glycine is made from serine via two related enzymatic processes. In the first
(Figure a below)
Biosynthesis of glycine from serine
(a) via serine hydroxymethyltransferase and
(b) via glycine oxidase.
serine hydroxymethyltransferase, a PLP-dependent enzyme, catalyzes the transfer of the serine b-carbon to tetrahydrofolate (THF), the principal agent of one-carbon metabolism . Glycine and N5,N10-methylene-THF are the
products. In addition, glycine can be synthesized by a reversal of the glycine oxidase reaction (Figure b above). Here, glycine is formed when N5,N10-methylene-THF condenses with NH4+ and CO2. Via this route, the b-carbon of serine becomes part of glycine. The conversion of serine to glycine is a prominent means of generating one-carbon derivatives of THF, which are so important for the biosynthesis of purines and the C-5 methyl group of thymine (a pyrimidine ), as well as the amino acid methionine. Glycine itself contributes to both purine and heme synthesis. 11
Glycine is made from serine via two related enzymatic processes. In the first, serine hydroxymethyltransferase, a PLP-dependent enzyme, catalyzes the transfer of the serine b-carbon to tetrahydrofolate (THF), the principal agent of one-carbon metabolism. Glycine and N5,N10-methylene-THF are the products.
Biosynthesis of glycine 6
Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme Serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate:[
Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate 7
Intermediates in energy production pathways such as glycolysis and the Kreb's cycle are commonly the starting point for the biosynthesis of amino acids. The glycolytic intermediate 3-phosphoglycerate is the starting point for the biosynthesis of serine and glycine. First, 3-phosphoglycerate is oxidized and then transaminated to produce 3-phosphoserine. Phosphoserine hydrolase hydrolyzes the phosphate in 3-phosphoserine to produce serine. The side chain carbon of serine is removed to create glycine, which has only hydrogen as its side chain. The removal of the serine side chain is accomplished by transferring the carbon to tetrahydrofolate, a carrier of one-carbon groups. Genetic deficiency of the first enzyme in the pathway, 3-phosphoglycerate dehydrogenase, leads to impaired myelination of neurons and impaired development of the central nervous system.
Intermediates in energy production pathways such as glycolysis and the Kreb's cycle are commonly the starting point for the biosynthesis of amino acids. The glycolytic intermediate 3-phosphoglycerate is the starting point for the biosynthesis of serine and glycine. First, 3-phosphoglycerate is oxidized and then transaminated to produce 3-phosphoserine.
Phosphoserine hydrolase hydrolyzes the phosphate in 3-phosphoserine to produce serine. The side chain carbon of serine is removed to create glycine, which has only hydrogen as its side chain. The removal of the serine side chain is accomplished by transferring the carbon to tetrahydrofolate, a carrier of one-carbon groups. Genetic deficiency of the first enzyme in the pathway, 3-phosphoglycerate dehydrogenase, leads to impaired myelination of neurons and impaired development of the central nervous system.
1. https://sci-hub.bz/http://www.nature.com/nchem/journal/v2/n11/full/nchem.827.html
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713413/
3. https://phys.org/news/2016-05-comet-glycine-key-recipe-life.html
4. http://reasonandscience.heavenforum.org/t1362-panspermia#1926
5. http://www.truthinscience.org.uk/tis2/index.php/evidence-for-evolution-mainmenu-65/51-the-miller-urey-experiment.html
6. http://en.wikipedia.org/wiki/Glycine
7. http://www.biocarta.com/pathfiles/GlycinePathway.asp
8. https://en.wikipedia.org/wiki/Glycine
9. http://what-when-how.com/molecular-biology/glycine-gly-g-molecular-biology/
10. https://en.wikipedia.org/wiki/3-Phosphoglyceric_acid
11. Biochemistry 6th ed. Garrett, page 907
12. https://en.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase
13. https://www.nature.com/articles/s41598-017-03807-5
14. https://www.genome.jp/kegg-bin/show_pathway?ec00260+1.1.1.95
15. https://www.frontiersin.org/articles/10.3389/fmolb.2018.00110/full
Glycine, serine and threonine metabolism 14The 3-Phosphoglycerate Family of Amino Acids Includes Ser, Gly, and Cys
Serine, glycine, and cysteine are derived from the glycolytic intermediate 3-Phosphoglyceric acid (3PG). Glycine is derived from Serine. 3-Phosphoglyceric acid (3PG) is the conjugate acid of glycerate 3-phosphate (GP). The glycerate is a biochemically significant metabolic intermediate in both glycolysis and the Calvin cycle. 10
Enzymes used in Glycolysis:
Hexokinase (EC 2.7.1.1 )
Phosphoglucose isomerase (EC 5.3.1.9 )
Phosphofructokinase (EC 2.7.1.11 )
Fructose-bisphosphate aldolase (EC 4.1.2.13 )
Triosephosphate isomerase (EC 5.3.1.1 )
Glyceraldehyde 3-phosphate dehydrogenase (EC 1.2.1.12 )
Phosphoglycerate kinase (EC 2.7.2.3 )
Phosphoglycerate mutase (EC 5.4.2.1 )
Enolase (EC 4.2.1.11 )
Pyruvate kinase (EC 2.7.1.40 )
In all non-photosynthetic organisms, including mammals, a major source of L-serine is the phosphorylated pathway of L-serine biosynthesis. 15 The pathway consists of three enzymes,
D-3-phosphoglycerate dehydrogenase (PGDH),
phosphoserine amino transferase (PSAT), and
L-phosphoserine phosphatase (PSP).
Phosphoglycerate dehydrogenase
http://en.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase
Phosphoserine transaminase
http://en.wikipedia.org/wiki/Phosphoserine_transaminase
Phosphoserine phosphatase
http://en.wikipedia.org/wiki/Phosphoserine_phosphatase
Serine hydroxymethyltransferase
http://en.wikipedia.org/wiki/Serine_hydroxymethyltransferase
(a) Schematic of the phosphorylated pathway; names of enzymes are underlined;
PGDH, 3-phosphoglycerate dehydrogenase;
PSAT, phosphoserine aminotransferase;
PSP, phosphoserine phosphatase;
3-PHP, 3-phosphohydroxypyruvate;
3-PS, 3-phosphoserine;
L-Glu,
L-glutamate;
2-OG, 2-oxoglutarate;
Pi, inorganic phosphate.
(b) Domain architectures and effectors of PGDH; the domains of PGDH proteins from archaea [S. tokodaii (StPGDH)], bacteria [E. coli (EcPGDH) and M. tuberculosis (MtPGDH)], cyanobacterium [A. halophytica (AhPGDH)], mammals [R. norvegicus (RnPGDH) and Homo sapiens (HsPGDH)], and plant [A. thaliana (AtPGDHs)] are schematically shown with highlighted catalytic, ACT, and ASB domains. Because ACT domains of HsPGDH and RnPGDH are not functional, they are indicated in white. Numbers in parenthesis indicate references. In ref. 14, HsPGDH was not inhibited by serine, although the data were not shown (“No ? ” in the figure).
The diversion of 3-phosphoglycerate. (3PG) from glycolysis is achieved via 3-phosphoglycerate dehydrogenase. 12 ( figure below )
3-phosphoglycerate dehydrogenase (PGDH) (EC 1.1.1.95)
3-Phosphoglycerate dehydrogenase catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the committed step in the phosphorylated pathway of L-serine biosynthesis. It is also essential in cysteine and glycine synthesis.
3-Phosphoglycerate dehydrogenase (PGDH) is activated by various biomolecules and indicate that serine biosynthesis is regulated by multiple pathways. 13
Biosynthesis of serine from 3-phosphoglycerate.
This NAD+-dependent oxidation of 3-PG yields 3-phosphohydroxypyruvate—which, as an a-keto acid, is a substrate for transamination by glutamate to give 3-phosphoserine (reaction 2, above). Serine phosphatase then generates serine (Figure above, reaction 3). Serine inhibits the first enzyme, 3-PG dehydrogenase, and thereby feedback-regulates its own synthesis. Glycine is made from serine via two related enzymatic processes. In the first
(Figure a below)
Biosynthesis of glycine from serine
(a) via serine hydroxymethyltransferase and
(b) via glycine oxidase.
serine hydroxymethyltransferase, a PLP-dependent enzyme, catalyzes the transfer of the serine b-carbon to tetrahydrofolate (THF), the principal agent of one-carbon metabolism . Glycine and N5,N10-methylene-THF are the
products. In addition, glycine can be synthesized by a reversal of the glycine oxidase reaction (Figure b above). Here, glycine is formed when N5,N10-methylene-THF condenses with NH4+ and CO2. Via this route, the b-carbon of serine becomes part of glycine. The conversion of serine to glycine is a prominent means of generating one-carbon derivatives of THF, which are so important for the biosynthesis of purines and the C-5 methyl group of thymine (a pyrimidine ), as well as the amino acid methionine. Glycine itself contributes to both purine and heme synthesis. 11
Glycine is made from serine via two related enzymatic processes. In the first, serine hydroxymethyltransferase, a PLP-dependent enzyme, catalyzes the transfer of the serine b-carbon to tetrahydrofolate (THF), the principal agent of one-carbon metabolism. Glycine and N5,N10-methylene-THF are the products.
Biosynthesis of glycine 6
Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme Serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate:[
Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate 7
Intermediates in energy production pathways such as glycolysis and the Kreb's cycle are commonly the starting point for the biosynthesis of amino acids. The glycolytic intermediate 3-phosphoglycerate is the starting point for the biosynthesis of serine and glycine. First, 3-phosphoglycerate is oxidized and then transaminated to produce 3-phosphoserine. Phosphoserine hydrolase hydrolyzes the phosphate in 3-phosphoserine to produce serine. The side chain carbon of serine is removed to create glycine, which has only hydrogen as its side chain. The removal of the serine side chain is accomplished by transferring the carbon to tetrahydrofolate, a carrier of one-carbon groups. Genetic deficiency of the first enzyme in the pathway, 3-phosphoglycerate dehydrogenase, leads to impaired myelination of neurons and impaired development of the central nervous system.
Intermediates in energy production pathways such as glycolysis and the Kreb's cycle are commonly the starting point for the biosynthesis of amino acids. The glycolytic intermediate 3-phosphoglycerate is the starting point for the biosynthesis of serine and glycine. First, 3-phosphoglycerate is oxidized and then transaminated to produce 3-phosphoserine.
Phosphoserine hydrolase hydrolyzes the phosphate in 3-phosphoserine to produce serine. The side chain carbon of serine is removed to create glycine, which has only hydrogen as its side chain. The removal of the serine side chain is accomplished by transferring the carbon to tetrahydrofolate, a carrier of one-carbon groups. Genetic deficiency of the first enzyme in the pathway, 3-phosphoglycerate dehydrogenase, leads to impaired myelination of neurons and impaired development of the central nervous system.
1. https://sci-hub.bz/http://www.nature.com/nchem/journal/v2/n11/full/nchem.827.html
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713413/
3. https://phys.org/news/2016-05-comet-glycine-key-recipe-life.html
4. http://reasonandscience.heavenforum.org/t1362-panspermia#1926
5. http://www.truthinscience.org.uk/tis2/index.php/evidence-for-evolution-mainmenu-65/51-the-miller-urey-experiment.html
6. http://en.wikipedia.org/wiki/Glycine
7. http://www.biocarta.com/pathfiles/GlycinePathway.asp
8. https://en.wikipedia.org/wiki/Glycine
9. http://what-when-how.com/molecular-biology/glycine-gly-g-molecular-biology/
10. https://en.wikipedia.org/wiki/3-Phosphoglyceric_acid
11. Biochemistry 6th ed. Garrett, page 907
12. https://en.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase
13. https://www.nature.com/articles/s41598-017-03807-5
14. https://www.genome.jp/kegg-bin/show_pathway?ec00260+1.1.1.95
15. https://www.frontiersin.org/articles/10.3389/fmolb.2018.00110/full
