In enzymology, a 3-mercaptopyruvate sulfurtransferase () is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that

catalyzes Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

the

chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...

s of 3-mercaptopyruvate. This enzyme belongs to the family of

transferase A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of ...

s, specifically the sulfurtransferases. This enzyme participates in

cysteine metabolism Cysteine metabolism refers to the biological pathways that consume or create cysteine. The pathways of different amino acids and other metabolites interweave and overlap to creating complex systems.cysteine is metabolism creating complex systems ...

. It is encoded by the ''MPST''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. The enzyme is of interest because it provides a pathway for detoxification of cyanide, especially since it occurs widely in the cytosol and distributed broadly.

Nomenclature

The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivial ...

of this enzyme class is 3-mercaptopyruvate:cyanide sulfurtransferase. This enzyme is also called beta-mercaptopyruvate sulfurtransferase and in the older literature, human liver rhodanese.

Structure

Gene

The '' MPST'' gene lies on the

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...

location of 22q12.3 and consists of 6

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...

. Alternatively spliced transcript variants encoding the same protein have been identified.

Protein

The encoded cytoplasmic protein is a member of the rhodanese family but is not rhodanese itself, which is found only in mitochondria. MPST protein consists of 317

amino acid residues Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer may ...

and weighs 35250Da. MPST contains two rhodanese domains with similar

secondary structure Protein secondary structure is the three dimensional form of ''local segments'' of proteins. The two most common secondary structural elements are alpha helices and beta sheets, though beta turns and omega loops occur as well. Secondary struct ...

s suggesting a common evolutionary origin. The catalytic

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

residue only exists in the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

rhodanese domain. The protein can function as a monomer or as a disulfide-linked homodimer.

Function and mechanism

The biological function of MPST remains unclear. It may be involved in cyanide detoxification, biosynthesis of thiosulfate, production of the signalling molecule hydrogen sulfide, or the degradation of cysteine. MPST reacts with 3-MP to convert a cysteinyl residue to the persulfide-containing intermediate: :RSH + HSCH₂C(O)CO₂⁻ → RSSH + CH₃C(O)CO₂⁻ The persulfide group is labile, and can transfer S to other groups, such as cyanide. It is also susceptible to reduction to release

hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The und ...

. H₂S is produced from l-cysteine by

cystathionine-γ-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 cystathionine into cysteine, 2-oxobutanoate ( α-ketobutyrate), and ...

(CSE) and MPST. l-cysteine-dependent production of H₂S by MPST is a two-step reaction. In the first step, cysteine transaminase converts l-cysteine along with α-ketoglutarate into 3-mercaptopyruvate (3-MP). Subsequently, MPST converts 3-MP into H₂S. MPST catalyzes the transfer of a sulfur atom from mercaptopyruvate to sulfur acceptors like cyanides or

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

compounds. Thus it is also considered to participate in cysteine degradation. MPST generates H₂S in

coronary artery The coronary arteries are the arterial blood vessels of coronary circulation, which transport oxygenated blood to the heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any other tissue or organ o ...

, mediating its effects through direct modulation of NO, namely vasodilation. This has important implications for H₂S-based therapy in healthy and diseased coronary arteries.

Biological significance

MPST is expressed in a number of tissues, including kidney, liver, lung, heart, muscle,

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, and brain. 3-

Mercaptopyruvate 3-Mercaptopyruvic acid is an intermediate in cysteine metabolism. It has been studied as a potential treatment for cyanide poisoning, but its half-life is too short for it to be clinically effective. Instead, prodrug A prodrug is a medication ...

(3-MP), along with α-ketoglutarate, is derived from cysteine by the action of an

aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α- keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid ...

. Thus MPST may participate in cysteine degradation.

Biomedical

Hydrogen sulfide production

H₂S is produced from MPST (as well as by

). MPST generates H₂S in

, mediating its effects through direct modulation of NO, namely vasodilation. This has important implications for H₂S-based therapy in healthy and diseased coronary arteries.

Mercaptolactate-cysteine disulfiduria

Deficiency in MPST has been found related to mercaptolactate-cysteine disulfiduria, a rare inheritable disorder associated with oversecretion of mercaptolactate-cysteine disulfide in urine. Immunoreactivity for MPST was detected in malignant

uroepithelium Transitional epithelium also known as urothelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching (stretchable epithelium). The transitional epithelium usually appears ...

and muscular layer of

bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become ma ...

samples. Protein levels and catalytic activities of MPST increased with the increase of malignant degrees in human bladder tissues and human urothelial cell carcinoma of bladder (UCB) cell lines and this may promote the application of MPST novel enzymes to UCB diagnosis or treatment.