Lean Body Mass Harbors Sensing Mechanisms That Allow Safeguarding of Methionine Homeostasis

Overview

Journal Nutrients

Date 2017 Sep 21

PMID 28930162

Citations 5

Authors

Yves Ingenbleek

Affiliations

Soon will be listed here.

Abstract

Protein-depleted states generate allosteric inhibition of liver cystathionine β-synthase (CBS), which governs the first enzymatic step of the transsulfuration cascade, resulting in upstream accretion of homocysteine (Hcy) in body fluids. A similar Hcy increase may arise from normal hepatocytes undergoing experimentally-induced impairment of betaine-homocysteine methyltransferase (BHTM) activity or from components of lean body mass (LBM) submitted to any inflammatory disorder. LBM comprises a composite agglomeration of extrarenal tissues characterized by naturally occurring BHTM inactivity. As a result of cellular injury, LBM releases high concentrations of Hcy into the extracellular space, contrasting with the disruption of normal remethylation pathways. Hyperhomocysteinemia acts as a biomarker, reflecting the severity of insult and operating as an alarm signal. Elevated Hcy levels constitute a precursor pool recognized by a CBS coding region that reacts to meet increased methionine requirements in LBM tissues, using its enhanced production in hepatocytes. Preservation of methionine homeostasis benefits from its high metabolic priority and survival value.

Citing Articles

Longitudinal Analysis of One-Carbon Metabolism-Related Metabolites in Maternal and Cord Blood of Japanese Pregnant Women.

Kubo Y, Fukuoka H, Shoji K, Mori C, Sakurai K, Nishikawa M Nutrients. 2024; 16(11).

PMID: 38892698 PMC: 11174998. DOI: 10.3390/nu16111765.

MuscleAtlasExplorer: a web service for studying gene expression in human skeletal muscle.

Asplund O, Rung J, Groop L, Prasad B R, Hansson O Database (Oxford). 2020; 2020.

PMID: 33338203 PMC: 7747357. DOI: 10.1093/database/baaa111.

Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects.

Ingenbleek Y Nutrients. 2019; 11(4).

PMID: 31010086 PMC: 6521094. DOI: 10.3390/nu11040895.

Combining Dietary Sulfur Amino Acid Restriction with Polyunsaturated Fatty Acid Intake in Humans: A Randomized Controlled Pilot Trial.

Olsen T, Ovrebo B, Turner C, Bastani N, Refsum H, Vinknes K Nutrients. 2018; 10(12).

PMID: 30477080 PMC: 6315936. DOI: 10.3390/nu10121822.

Diagnostic Criteria and Clinical Outcomes in Sarcopenia Research: A Literature Review.

Han A, Bokshan S, Marcaccio S, DePasse J, Daniels A J Clin Med. 2018; 7(4).

PMID: 29642478 PMC: 5920444. DOI: 10.3390/jcm7040070.

References

OPPEHNEIMER J, SURKS M, Bernstein G, SMITY J . METABOLISM OF IODINE-131--LABELED THYROXINE-BINDING PREALBUMIN IN MAN. Science. 1965; 149(3685):748-50. DOI: 10.1126/science.149.3685.748. View

Illner K, Brinkmann G, Heller M, Bosy-Westphal A, Muller M . Metabolically active components of fat free mass and resting energy expenditure in nonobese adults. Am J Physiol Endocrinol Metab. 2000; 278(2):E308-15. DOI: 10.1152/ajpendo.2000.278.2.E308. View

Storch K, Wagner D, Burke J, Young V . Quantitative study in vivo of methionine cycle in humans using [methyl-2H3]- and [1-13C]methionine. Am J Physiol. 1988; 255(3 Pt 1):E322-31. DOI: 10.1152/ajpendo.1988.255.3.E322. View

McNurlan M, Sandgren A, Hunter K, Essen P, Garlick P, Wernerman J . Protein synthesis rates of skeletal muscle, lymphocytes, and albumin with stress hormone infusion in healthy man. Metabolism. 1996; 45(11):1388-94. DOI: 10.1016/s0026-0495(96)90120-1. View

Stead L, Brosnan M, Brosnan J . Characterization of homocysteine metabolism in the rat liver. Biochem J. 2000; 350 Pt 3:685-92. PMC: 1221298. View

Studer M, Barbaud A, Truchetet F, Nguyen P, Bursztejn A, Schmutz J . [Hyperhomocysteinemia and leg ulcers: A prospective study of 68 patients]. Ann Dermatol Venereol. 2011; 138(10):645-51. DOI: 10.1016/j.annder.2011.05.009. View

Breitkreutz R, Holm S, Pittack N, Beichert M, Babylon A, Yodoi J . Massive loss of sulfur in HIV infection. AIDS Res Hum Retroviruses. 2000; 16(3):203-9. DOI: 10.1089/088922200309296. View

Katko M, Zavaczki E, Jeney V, Paragh G, Balla J, Varga Z . Homocysteine metabolism in peripheral blood mononuclear cells: evidence for cystathionine beta-synthase activity in resting state. Amino Acids. 2011; 43(1):317-26. DOI: 10.1007/s00726-011-1080-2. View

Ruud E, Holmstrom H, Brosstad F, Wesenberg F . Children with acute lymphoblastic leukaemia have high plasma levels of total homocysteine at time of diagnosis. Scand J Clin Lab Invest. 2006; 66(1):67-78. DOI: 10.1080/00365510500453003. View

10.

Teng Y, Mehedint M, Garrow T, Zeisel S . Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas. J Biol Chem. 2011; 286(42):36258-67. PMC: 3196139. DOI: 10.1074/jbc.M111.265348. View

11.

Tang B, Mustafa A, Gupta S, Melnyk S, James S, Kruger W . Methionine-deficient diet induces post-transcriptional downregulation of cystathionine β-synthase. Nutrition. 2009; 26(11-12):1170-5. PMC: 2956870. DOI: 10.1016/j.nut.2009.10.006. View

12.

Brozek J, Grande F . Body composition and basal metabolism in man: correlation analysis versus physiological approach. Hum Biol. 1955; 27(1):22-31. View

13.

Fernandez-Miranda C, Manzano M, Fernandez I, Lopez-Alonso G, Gomez P, Ayala R . [Association of hyperhomocysteinemia with liver steatosis in patients with chronic hepatitis C]. Med Clin (Barc). 2010; 136(2):45-9. DOI: 10.1016/j.medcli.2010.05.024. View

14.

Fuller M, McWilliam R, Wang T, Giles L . The optimum dietary amino acid pattern for growing pigs. 2. Requirements for maintenance and for tissue protein accretion. Br J Nutr. 1989; 62(2):255-67. DOI: 10.1079/bjn19890028. View

15.

Finkelstein J, Martin J . Methionine metabolism in mammals. Adaptation to methionine excess. J Biol Chem. 1986; 261(4):1582-7. View

16.

Koebnick C, Garcia A, Dagnelie P, Strassner C, Lindemans J, Katz N . Long-term consumption of a raw food diet is associated with favorable serum LDL cholesterol and triglycerides but also with elevated plasma homocysteine and low serum HDL cholesterol in humans. J Nutr. 2005; 135(10):2372-8. DOI: 10.1093/jn/135.10.2372. View

17.

Brattstrom L, Lindgren A, Israelsson B, MALINOW M, Norrving B, Upson B . Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Invest. 1992; 22(3):214-21. DOI: 10.1111/j.1365-2362.1992.tb01829.x. View

18.

Muller M, Bosy-Westphal A, Kutzner D, Heller M . Metabolically active components of fat-free mass and resting energy expenditure in humans: recent lessons from imaging technologies. Obes Rev. 2002; 3(2):113-22. DOI: 10.1046/j.1467-789x.2002.00057.x. View

19.

Malmezat T, Breuille D, Capitan P, Mirand P, Obled C . Glutathione turnover is increased during the acute phase of sepsis in rats. J Nutr. 2000; 130(5):1239-46. DOI: 10.1093/jn/130.5.1239. View

20.

Pey A, Majtan T, Sanchez-Ruiz J, Kraus J . Human cystathionine β-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM. Biochem J. 2012; 449(1):109-21. DOI: 10.1042/BJ20120731. View