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Cysteine S-conjugate β-lyases

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Summary.

Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate-containing enzymes that catalyze β-elimination reactions with cysteine S-conjugates that possess an electron-withdrawing group attached at the sulfur. The end products of the β-lyase reaction are pyruvate, ammonium and a sulfur-containing fragment. If the sulfur-containing fragment is reactive, the parent cysteine S-conjugate may be toxic, particularly to kidney mitochondria. Halogenated alkenes are examples of electrophiles that are bioactivated (toxified) by conversion to cysteine S-conjugates. These conjugates are converted by cysteine S-conjugate β-lyases to thioacylating fragments. Several cysteine S-conjugates found in allium foods (garlic and onion) are β-lyase substrates. This finding may account in part for the chemopreventive activity of allium products. This review (1) identifies enzymes that catalyze cysteine S-conjugate β-lyase reactions, (2) suggests that toxicant channeling may contribute to halogenated cysteine S-conjugate-induced toxicity to mitochondria, and (3) proposes mechanisms that may contribute to the antiproliferative effects of sulfur-containing fragments eliminated from allium-derived cysteine S-conjugates.

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Abbreviations

AlaAT:

alanine aminotransferase

AGAT II:

alanine-glyoxylate aminotransferase isoenzyme II

BCATc:

cytosolic branched-chain aminotransferase

BCATm:

mitochondrial branched-chain aminotransferase

BCDHC:

branched-chain α-keto acid dehydrogenase complex

BTC:

S-(2-benzothiazolyl)-L-cysteine

cytAspAT:

cytosolic aspartate aminotransferase

DCVC:

S-(1,2-dichlorovinyl)-L-cysteine

GST:

glutathione S-transferase

GTK:

glutamine transaminase K

KAT I:

kynurenine aminotransferase isoenzyme I

KGDHC:

α-ketoglutarate dehydrogenase complex

mitAspAT:

mitochondrial aspartate aminotransferase

PDHC:

pyruvate dehydrogenase complex

PLP:

pyridoxal 5′-phosphate

PMP:

pyridoxamine 5′-phosphate

SAC:

S-allyl-L-cysteine

SAMC:

S-allylmercapto-L-cysteine

TCA cycle:

tricarboxylic acid cycle

TFEC:

S-(1,1,2,2-tetrafluoroethyl)-L-cysteine

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Cooper, A., Pinto, J. Cysteine S-conjugate β-lyases. Amino Acids 30, 1–15 (2006). https://doi.org/10.1007/s00726-005-0243-4

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