PathBank

Pathway Description

Glycine and Serine Metabolism

Bos taurus

Category:

Metabolite Pathway

Sub-Category:

Metabolic

Created: 2018-08-10

Last Updated: 2019-08-30

This pathway describes the synthesis and breakdown of several small amino acids, including glycine, serine, and cysteine. All of these compounds share common intermediates and almost all can be biosynthesized from one another. Serine and glycine are not essential amino acids and can be synthesized from several routes. On the other hand, cysteine is a conditionally essential amino acid, meaning that it can be endogenously synthesized but insufficient quantities may be produced due to certain diseases or conditions. Serine is central to the synthesis and breakdown of the other two amino acids. Serine can be synthesized via glycerate, which can be converted into glycerate 3-phosphate (via glycerate kinase), which in turn is converted into phosphohydroxypyruvate by phosphoglycerate dehydrogenase and then phosphoserine (via phosphoserine transaminase) and finally to serine (via phosphoserine phosphatase). The serine synthesized via this route can be used to create cysteine and glycine through the homocysteine cycle. In the homocysteine cycle, cystathionine beta-synthase catalyzes the condensation of homocysteine and serine to give cystathionine. Cystathionine beta-lyase then converts this double amino acid to cysteine, ammonia, and alpha-ketoglutarate. Glycine is biosynthesized in the body from the amino acid serine. In most organisms, the enzyme serine hydroxymethyltransferase (SHMT) catalyzes this transformation using tetrahydrofolate (THF), leading to methylene THF and glycine. Glycine can be degraded via three pathways. The predominant pathway in animals involves the glycine cleavage system, also known as the glycine decarboxylase complex or GDC. This system is usually triggered in response to high concentrations of glycine. The system is sometimes referred to as glycine synthase when it runs in the reverse direction to produce glycine. The glycine cleavage system consists of four weakly interacting proteins: T, P, L and H-proteins. The glycine cleavage system leads to the degradation of glycine into ammonia and CO2. In the second pathway, glycine is degraded in two steps. The first step in this degradation pathway is the reverse of glycine biosynthesis from serine with serine hydroxymethyltransferase (SHMT). The serine generated via glycine is then converted into pyruvate by the enzyme known as serine dehydratase. In the third route to glycine degradation, glycine is converted into glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase into oxalate in an NAD+-dependent reaction.

References

Glycine and Serine Metabolism References

Powell JF, Hsu YP, Weyler W, Chen SA, Salach J, Andrikopoulos K, Mallet J, Breakefield XO: The primary structure of bovine monoamine oxidase type A. Comparison with peptide sequences of bovine monoamine oxidase type B and other flavoenzymes. Biochem J. 1989 Apr 15;259(2):407-13. doi: 10.1042/bj2590407.

Pubmed: 2719656

Guan KL, Weiner H: Sequence of the precursor of bovine liver mitochondrial aldehyde dehydrogenase as determined from its cDNA, its gene, and its functionality. Arch Biochem Biophys. 1990 Mar;277(2):351-60. doi: 10.1016/0003-9861(90)90590-u.

Pubmed: 1689984

Farres J, Guan KL, Weiner H: Primary structures of rat and bovine liver mitochondrial aldehyde dehydrogenases deduced from cDNA sequences. Eur J Biochem. 1989 Mar 1;180(1):67-74. doi: 10.1111/j.1432-1033.1989.tb14616.x.

Pubmed: 2540003

Lee JE, Cho YD: Purification and characterization of bovine brain gamma-aminobutyraldehyde dehydrogenase. Biochem Biophys Res Commun. 1992 Nov 30;189(1):450-4.

Pubmed: 1449496

Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.

Pubmed: 19393038

Okamura-Ikeda K, Fujiwara K, Yamamoto M, Hiraga K, Motokawa Y: Isolation and sequence determination of cDNA encoding T-protein of the glycine cleavage system. J Biol Chem. 1991 Mar 15;266(8):4917-21.

Pubmed: 2002038

Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.

Pubmed: 16305752

This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.

Propagated from SMP0000004

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		(R)-lipoic acid
		2-Ketobutyric acid
		3-Phosphoglyceric acid
		5,10-Methylene-THF
		5-Aminolevulinic acid
		8-[(Aminomethyl)sulfanyl]-6-sulfanyloctanoic acid
		Acetyl-CoA
		Adenosine diphosphate
		Adenosine monophosphate
		Adenosine triphosphate
		Aminoacetone
		Ammonia
		Carbon dioxide
		Coenzyme A
		Creatine
		D-Serine
		Dihydrolipoate
		Dimethylglycine
		FAD
		Formaldehyde
		Glyceric acid
		Glycine
		Glyoxylic acid
		Guanidoacetic acid
		Homocysteine
		Hydrogen peroxide
		Hydroxypyruvic acid
		L-2-Amino-3-oxobutanoic acid
		L-Alanine
		L-Arginine
		L-Cystathionine
		L-Cysteine
		L-Glutamic acid
		L-Methionine
		L-Serine
		Magnesium
		NAD
		NADH
		Orotidylic acid
		Oxoglutaric acid
		Oxygen
		Phosphate
		Phosphohydroxypyruvic acid
		Phosphoserine
		Pyridoxal 5'-phosphate
		Pyrophosphate
		Pyruvaldehyde
		Pyruvic acid
		S-Adenosylhomocysteine
		S-Adenosylmethionine
		Sarcosine
		Succinyl-CoA
		Tetrahydrofolic acid
		Water
		Zinc (II) ion
		βine

Visualize Protein Data

		2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial
		5-aminolevulinate synthase, nonspecific, mitochondrial
		Aldehyde dehydrogenase, mitochondrial
		Amine oxidase [flavin-containing] A
		Aminomethyltransferase, mitochondrial
		Betaine--homocysteine S-methyltransferase 1
		Cystathionine beta-synthase
		Cystathionine gamma-lyase
		D-3-phosphoglycerate dehydrogenase
		Dihydrolipoyl dehydrogenase
		GARS protein
		Glycerate kinase
		Glycine amidinotransferase, mitochondrial
		Glycine cleavage system P protein
		Glycine N-methyltransferase
		Guanidinoacetate N-methyltransferase
		L-serine dehydratase/L-threonine deaminase
		Phosphoserine aminotransferase
		Phosphoserine phosphatase
		Pyruvate dehydrogenase phosphatase regulatory subunit, mitochondrial
		Serine hydroxymethyltransferase, cytosolic
		Serine hydroxymethyltransferase, mitochondrial
		Serine racemase
		Serine--pyruvate aminotransferase
		Serine--tRNA ligase, cytoplasmic