Cystathionine gamma-lyase

The enzyme cystathionine γ-lyase (EC 4.4.1.1, CTH or CSE; also cystathionase; systematic name L-cystathionine cysteine-lyase (deaminating; 2-oxobutanoate-forming)) breaks down

Pyridoxal phosphate is a prosthetic group of this enzyme.^[1][2][3]

Cystathionine γ-lyase also catalyses the following elimination reactions:

• L-homoserine to form H₂O, NH₃ and 2-oxobutanoate
• L-cystine, producing thiocysteine, pyruvate and NH₃^[4]
• L-cysteine producing pyruvate, NH₃ and H₂S

In some bacteria and mammals, including humans, this enzyme takes part in generating hydrogen sulfide.^[2][5] Hydrogen sulfide is one of a few gases that was recently discovered to have a role in cell signaling in the body.^[6]

Enzyme mechanism

Cystathionase uses pyridoxal phosphate to facilitate the cleavage of the sulfur-gamma carbon bond of cystathionine, resulting in the release of cysteine.

Cystathionine gamma lyase also shows gamma-synthase activity depending on the concentrations of reactants present.[8] The mechanisms are the same until they diverge after formation of the vinyl glyoxylate derivative. In the gamma synthase mechanism, the gamma carbon is attacked by a sulfur nucleophile, resulting in the formation of a new sulfur-gamma carbon bond.^[7][8]

Enzyme structure

Cystathionine γ-lyase is a member of the Cys/Met metabolism PLP-dependent enzymes family. Other members include cystathionine γ synthase, cystathionine β lyase, and methionine γ lyase.

Pyridoxal phosphate is bound in the active site by Lys²¹².[2]

Disease relevance

Cysteine is the

Mutations and deficiencies in cystathionase are associated with cystathioninuria. The mutations T67I and Q240E weaken the enzyme's affinity for pyridoxal phosphate, the co-factor vital to enzymatic function.^[2] Low levels of H₂S have also been associated with hypertension in mice.^[10]

• Cysteine metabolism

References