3'-Phosphoadenosine-5'-phosphosulfate

3'-Phosphoadenosine-5'-phosphosulfate

3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is a critical coenzyme involved in the sulfation process, which is essential for the metabolism of various biomolecules. It serves as the universal sulfate donor in biological systems, facilitating the transfer of sulfate groups to a wide range of substrates, including proteins, lipids, and carbohydrates.

Structure

PAPS is a nucleotide derivative composed of an adenosine moiety linked to a 5'-phosphosulfate group. The structure of PAPS can be represented as a combination of adenosine monophosphate (AMP) and a sulfate group, connected via a phosphodiester bond. This unique structure allows PAPS to function effectively as a sulfate donor in enzymatic reactions.

Biosynthesis

The biosynthesis of PAPS occurs in two main steps:

1. Formation of Adenosine 5'-Phosphosulfate (APS): The enzyme ATP sulfurylase catalyzes the reaction between adenosine triphosphate (ATP) and inorganic sulfate to form APS and pyrophosphate.
2. Conversion to PAPS: APS is then phosphorylated by the enzyme APS kinase to form PAPS. This step involves the transfer of a phosphate group from ATP to APS, resulting in the formation of PAPS.

Function

PAPS functions as a sulfate donor in various sulfotransferase reactions. These reactions are catalyzed by a family of enzymes known as sulfotransferases, which transfer the sulfate group from PAPS to specific substrates. This process is crucial for the modification and detoxification of endogenous and exogenous compounds, including hormones, drugs, and xenobiotics.

Biological Importance

The sulfation process mediated by PAPS is vital for several physiological functions:

• Detoxification: Sulfation enhances the solubility of hydrophobic compounds, facilitating their excretion from the body.
• Hormone Regulation: Sulfation modulates the activity of hormones such as estrogens and thyroid hormones, influencing their biological activity and metabolism.
• Structural Integrity: Sulfation of glycosaminoglycans is essential for maintaining the structural integrity of connective tissues.

Clinical Significance

Deficiencies or abnormalities in PAPS synthesis or utilization can lead to various metabolic disorders. For instance, defects in sulfation pathways are associated with conditions such as mucopolysaccharidoses and chondrodysplasias. Understanding the role of PAPS in these processes is crucial for developing therapeutic strategies.

Related pages

• Sulfotransferase
• Adenosine triphosphate
• Sulfation
• Metabolism

Gallery

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  Chemical structure of 3'-Phosphoadenosine-5'-phosphosulfate

3'-Phosphoadenosine-5'-phosphosulfate

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  Chemical structure of 3'-Phosphoadenosine-5'-phosphosulfate