Project Materials

ANALYSIS OF 3-MERCAPTOPYRUVATE SULFURTRANSFERASE (3-MST)

CHAPTER ONE

INTRODUCTION

Among the primary metabolic enzymes that scientists are particularly interested in is 3-Mercaptopyruvate Sulphur Transferase (3-MST). Nature contains large amounts of this enzyme (Bordo, 2002 and Jarabak, 1981).

Numerous creatures, including humans, rodents, fish, and insects, have been found to exhibit it. The detoxification of cyanide, a strong toxin of the mitochondrial respiratory chain, has been the focus of this mitochondrial enzyme (Nelson et al., 2000).

The most crucial of the several metabolic enzymes involved in xenobiotic detoxification is 3-mercaptopyruvate sulfurtransferase. 3-mercaptopyruvate sulfurtransferase mediates the transfer of sulphur ions to cyanide or other thiol compounds, which aids in cyanide detoxification (Vandenet al., 1967).

It is also necessary for thiosulphate biosynthesis. It is crucial for the production of hydrogen sulphide in the brain, retina, and vascular endothelial cells, and it aids in the catabolism of cysteine when combined with cysteine aminotransferase (Shibuya et al., 2009).

In the atmosphere under oxidising conditions, it also developed several activities like defence against oxidative stress and redox control (maintenance of cellular redox homeostasis). (2005) Nagahara et al.

According to Hosokie et al. (1997), hydrogen sulphide (H2S) is a crucial neuroprotectant, smooth muscle contractor, signalling molecule, and synaptic modulator.

Calcium ions control its synthesis via the cysteine aminotransferase and 3-mercaptopyruvate sulfurtransferase pathways (Hosokie et al., 1997).

This enzyme is typically present in organisms that have been subjected to cyanide poisoning. This could be in food as in the cyanogenicglucosides being ingested. Numerous sources, including bacteria, yeasts, plants, and animals, have been used to study it (Marcus Wischik, 1998).

As a defensive strategy, cyanide might be injected into tree bark. Their parts (leaves, flowers, stems, roots, and fruits) are poisonous or repulsive to predators due to a variety of defence chemicals.

However, in reaction, the animals that consume them have developed a variety of defence mechanisms over the course of many generations, enabling them to safely consume the plant.

The range of defences that plants can employ is exemplified by the trunk of a tree (Marcus Wischik, 1998). Because of their surroundings, Oryctes rhinoceros larvae are among the creatures that are also susceptible to cyanide toxicity.

1.2. SULFURTRANSFERASE 3-MERCAPTOPYRUVATE

3-Mercaptopyruvate sulfurtransferase (EC. 2.8.1.2) belongs to the class of ubiquitous prokaryotic and eukaryotic enzymes known as sulfurtransferases (EC 2.8.1.1–5) (Bordo and Bork, 2002).

3. Mercaptopyruvate One of the enzymes involved in the cysteine catabolic pathway is sulfurtransferase. 3-mercaptopyruvate is converted to pyruvate and H2S by the enzyme (Shibuya et al., 2009).

Elevated urine concentrations of 3-mercaptopyruvate and 3-mercaptolactate, both in the form of disulphides with cysteine, are the consequence of this enzyme shortage (Crawhallet al., 1969). The chemical process is catalysed by it:

3. pyruvate + thiocyanate á mercaptopyruvate + cyanide

3. thiolà pyruvate + hydrogen sulphide + mercaptopyruvate (Sorbo 1957).

It contributes to cysteine metabolism and transfers sulfur-containing groups (Shibuya et al., 2013). Sulfane sulphur is transferred from a donor molecule, like thiosulphate or 3-mercaptopyruvate, to a nucleophile acceptor, like cyanide or mercptoethanol, via this enzyme.

The known sulphur-donor substrate for 3-mercaptopyruvate sulfurtransferase is 3-mercaptopyruvate (Porter & Baskin, 1995). Because 3-mercaptopyruvate sulfurtransferase can transfer sulphur from 3-mercaptopyruvate (3-MP) to cyanide (CN), creating the less toxic thiocyanate (SCN)

it is thought to be involved in the endogenous cyanide (CN) detoxification system (Hylin and Wood, 1959). It is a crucial enzyme for the brain’s production of hydrogen sulphide (H2S) (Shibuya et al., 2009).

This type of enzyme is known by its systematic name, 3-mercaptopyruvate: cyanide sulfurtransferase. Beta-mercaptopyruvatesulfurtransferase is another name for it (Vachek and Wood, 1972). It is one among the three enzymes in the body that are known to produce H2S (Hylin and Wood, 1959). The mitochondria are where it is mostly found (Cipollone et al., 2008).

According to unpublished findings, 3-MST expression levels are higher in the foetal and postnatal brains than in the adult brain, despite the promoter region exhibiting traits of a normal housekeeping gene (Nagahara et al., 2004).

The discovery that 3-MST expression in the cerebellum declines with age lends credence to the observation (Shibuya et al., 2013).

On the other hand, its expression level in the lung declines from the perinatal period. These findings imply that 3-MST may have a role in the brains of foetuses and newborns.

According to research, serotonin signalling through the brain’s 5-HT1A receptor during the early stages of development is essential for the formation of innate anxiety (Richardson-Jones et al., 2011).

In rat, 3-MST exhibits 2 redox-sensing molecular switches (Nagahara and Katayama, 2005). An intersubunit disulphide bond and a catalytic-site cysteine function as a thioredoxin-specific molecular switch (Nagahara et al., 2007).

Prokaryotes and plants, which sprang into the environment under reducing conditions, do not exhibit the intermolecular switch (Nagahara, 2013).

In the atmosphere under oxidising conditions, it therefore developed several activities, including defence against oxidative stress and redox control (maintenance of cellular redox homeostasis) (Nagahara et al., 2005).

Furthermore, 3-MST has the ability to produce H2S (or HS−) as a biofactor, which is likewise produced by cystathionine β-synthase and cystathionine γ-lyase (Abe and Kimura, 1996).

Remarkably, 3-MST is the only one that can generate SOx in the redox cycle of persulfide generated at the low-redox catalytic site cysteine (Nagahara et al., 2012).

An additional theory on the pathophysiology of the symptoms is that while SOx and/or H2S (or HS−) may inhibit anxiety-like behaviour, flaws in these molecules may cause anxiety-like behaviour to increase.

To measure H2S (or HS−) and SOx at the physiological level, however, no microanalysis technique has been developed (Ampola et al., 1969).

MCDU was first recognized and reported in 1968 as an inherited metabolic disorder caused by congenital 3-MST insufficiency or deficiency. Although the pathogenesis is still unknown, mental retardation was linked to the majority of cases (Ampola et al., 1969).