Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
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James D. Finkelstein
Abstract
In mammalian liver, two intersecting pathways, remethylation and transsulfuration, compete for homocysteine that has been formed from methionine. Remethylation of homocysteine, employing either methyltetrahydrofolate or betaine as the methyl donor, forms a methionine cycle that functions to conserve methionine. In contrast, the transsulfuration sequence – cystathionine synthase and cystathionase – serves to irreversibly catabolize the homocysteine while synthesizing cysteine. The rate of homocysteine formation and its distribution between these two pathways are the sites for metabolic regulation and coordination. The mechanisms for regulation include both the tissue content and the kinetic properties of the component enzymes as well as the concentrations of their substrates and other metabolic effectors. Adenosylmethionine and adenosylhomocysteine are important regulatory metabolites and may use one or more mechanisms to affect the enzymes. Adenosylmethionine is a positive effector of its own synthesis, cystathionine synthase and glycine methyltransferase but impairs both homocysteine methylases. Thus, the concentration of adenosylmethionine may be self-regulatory in mammalian liver. By means of other enzymatic mechanisms, the hepatic concentration of adenosylhomocysteine, an index of homocysteine accumulation, is also self-regulated. These considerations pertain primarily to liver, which has the unique capacity to synthesize more adenosylmethionine in the presence of excess methionine. However, there are organ-specific patterns of methionine metabolism and its regulation. All tissues possess the methionine cycle with methyltetrahydrofolate as the methyl donor but only liver, kidney, pancreas, intestine and brain also contain the transsulfuration pathway. The limitation of adenosylmethionine concentrations may make adenosylhomocysteine a more significant metabolic regulator in extrahepatic tissues. However, estimates of regulatory changes based on determinations of the plasma concentrations of the two metabolites are of limited value and must be used with caution. In addition, the recent description of “cystathionine (CBS) domains” in proteins not involved with methionine metabolism raises the possibility that abnormal concentrations of the adenosyl metabolites may impact on other metabolic pathways.
Clin Chem Lab Med 2007;45:1694–9.
©2007 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Homocysteine research: alive and kicking!
- Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
- Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
- The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
- Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
- Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
- The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
- Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
- Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
- Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
- Hyperhomocysteinemia, DNA methylation and vascular disease
- Measuring subclinical atherosclerosis: is homocysteine relevant?
- Plasma protein homocysteinylation in uremia
- Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
- Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
- Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
- Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
- The molecular basis of homocysteine thiolactone-mediated vascular disease
- Importance of folate-homocysteine homeostasis during early embryonic development
- Association between homocysteine, vitamin B6 concentrations and inflammation
- Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
- Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
- Haptocorrin in humans
- Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
- Decreased p66Shc promoter methylation in patients with end-stage renal disease
- Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
- Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
- The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial
- Acknowledgement
- Contents, Volume 45, 2007
- Author Index
- Subject Index
Articles in the same Issue
- Homocysteine research: alive and kicking!
- Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
- Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial
- Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
- The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases
- Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review
- Biomarkers of folate and vitamin B12 status in cerebrospinal fluid
- The role of hyperhomocysteinemia as well as folate, vitamin B6 and B12 deficiencies in osteoporosis – a systematic review
- Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
- Homocysteine, left ventricular dysfunction and coronary artery disease: is there a link?
- Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease
- Hyperhomocysteinemia, DNA methylation and vascular disease
- Measuring subclinical atherosclerosis: is homocysteine relevant?
- Plasma protein homocysteinylation in uremia
- Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease
- Hyperhomocysteinemia – association with renal transsulfuration and redox signaling in rats
- Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine
- Defects in homocysteine metabolism: diversity among hyperhomocyst(e)inemias
- The molecular basis of homocysteine thiolactone-mediated vascular disease
- Importance of folate-homocysteine homeostasis during early embryonic development
- Association between homocysteine, vitamin B6 concentrations and inflammation
- Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry
- Holotranscobalamin in laboratory diagnosis of cobalamin deficiency compared to total cobalamin and methylmalonic acid
- Haptocorrin in humans
- Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase
- Decreased p66Shc promoter methylation in patients with end-stage renal disease
- Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling
- Differential expression of γ-aminobutyric acid receptor A (GABAA) and effects of homocysteine
- The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial
- Acknowledgement
- Contents, Volume 45, 2007
- Author Index
- Subject Index
