The quantitative significance of the transsulfuration enzymes for H2S production in murine tissues.
The enzymes of the transsulfuration pathway, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are important for the endogenous production of hydrogen sulfide (H(2)S), a gaseous signaling molecule. The relative contributions of CBS and CSE to H(2)S generation in different tissues are not known. In this study, we report quantification of CBS and CSE in murine liver and kidney and their contribution to H(2)S generation in these tissues and in brain at saturating substrate concentrations. We show that CBS protein levels are significantly lower than those of CSE; 60-fold and 20-fold in liver and kidney, respectively. Each enzyme is more abundant in liver compared with kidney, twofold and sixfold for CBS and CSE, respectively. At high substrate concentrations (20 mM each cysteine and homocysteine), the capacity for liver H(2)S production is approximately equal for CBS and CSE, whereas in kidney and brain, CBS constitutes the major source of H(2)S, accounting for ∼80% and ∼95%, respectively, of the total output. At physiologically relevant concentrations of substrate, and adjusting for the differences in CBS versus CSE levels, we estimate that CBS accounts for only 3% of H(2)S production by the transsulfuration pathway enzymes in liver.
Biological Chemistry Department, University of Michigan Medical Center, Ann Arbor, Michigan, 48109-0600, USA.
Omer
O
Kabil
Victor
V
Vitvitsky
Peter
P
Xie
Ruma
R
Banerjee
D000818:Animals; D015153:Blotting, Western; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013455:Sulfur / Q000378:metabolism*
D013455:Sulfur; D006862:Hydrogen Sulfide
Science. 1966 May 6;152(3723):776-8
17797452
Crit Rev Toxicol. 1984;13(1):25-97
6378532
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15560-5
17878306
Life Sci. 1997;61(13):1205-15
9324062
J Biol Chem. 2009 Aug 14;284(33):22457-22466
19531479
FEBS J. 2008 Jul;275(13):3352-61
18494801
J Neurochem. 2008 Aug;106(4):1577-85
18513201
J Nutr. 2002 Nov;132(11):3369-78
12421853
Science. 2005 Apr 22;308(5721):518
15845845
Antioxid Redox Signal. 2010 May 1;12(9):1111-23
19803743
EMBO J. 2001 Nov 1;20(21):6008-16
11689441
Antioxid Redox Signal. 2010 May 15;12(10):1203-17
19769484
J Biol Chem. 2007 Jan 19;282(3):1561-9
17130129
Am J Physiol Regul Integr Comp Physiol. 2010 Jan;298(1):R51-60
19889863
J Clin Invest. 1999 Oct;104(8):1107-14
10525049
PLoS One. 2008;3(12):e4032
19107218
J Biol Chem. 1999 Oct 29;274(44):31256-60
10531322
J Neurosci. 1996 Feb 1;16(3):1066-71
8558235
Circulation. 2009 Sep 8;120(10):888-96
19704099
J Nutr. 1982 May;112(5):1011-8
7077413
J Biol Chem. 2009 Apr 24;284(17):11601-12
19261609
Antioxid Redox Signal. 2005 May-Jun;7(5-6):547-59
15890000
Am J Physiol Renal Physiol. 2009 Jul;297(1):F27-35
19439522
Biochemistry. 2008 Jun 10;47(23):6226-32
18476726
J Comp Neurol. 2007 Nov 10;505(2):158-65
17853447
Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1479-85
18799635
Biochim Biophys Acta. 2009 Jul;1787(7):856-63
19361483
J Biol Chem. 1998 Sep 25;273(39):25179-84
9737978
Trends Pharmacol Sci. 2008 Feb;29(2):84-90
18180046
J Nutr Biochem. 1990 May;1(5):228-37
15539209
J Biol Chem. 1994 Oct 14;269(41):25283-8
7929220
Am J Physiol Regul Integr Comp Physiol. 2004 Jul;287(1):R39-46
15016621
Antioxid Redox Signal. 2011 Jul 15;15(2):379-91
21028947
Biol Pharm Bull. 1994 Dec;17(12):1535-42
7735193
Biochemistry. 2006 Nov 14;45(45):13528-36
17087506
FASEB J. 2007 Jun;21(8):1699-706
17314140
Antioxid Redox Signal. 2009 Apr;11(4):703-14
18855522
Biochim Biophys Acta. 1973 May 28;304(3):765-73
4726857
J Neurochem. 2010 Apr;113(1):14-26
20067586
Science. 2008 Oct 24;322(5901):587-90
18948540
J Biol Chem. 1965 Nov;240(11):4382-92
4954368
J Biol Chem. 2010 Jul 16;285(29):21903-7
20448039
J Biol Chem. 2004 Nov 19;279(47):49199-205
15347670