Sulfur is an element for all known life, forming a component of essential amino acids, coenzymes, and vitamins. Organisms have developed metabolic pathways to acquire and incorporate this element into various biomolecules. These pathways are driven by enzymes that facilitate specific chemical reactions. One such enzyme is central to how many organisms process sulfur from their environment, performing the first step in a series of reactions that make environmental sulfur useful for biological processes.
What is ATP Sulfurylase?
ATP sulfurylase, also known by the systematic name ATP:sulfate adenylyltransferase, is an enzyme that initiates the metabolic use of inorganic sulfate. It belongs to the family of transferase enzymes, a nucleotidyltransferase because it transfers a nucleotide group. The primary function of this enzyme is to catalyze the activation of sulfate, an ion, making it chemically ready for subsequent biological reactions. This activation is the first dedicated step in the process of assimilating inorganic sulfate into organic molecules.
As a protein, ATP sulfurylase has a specific three-dimensional structure that allows it to bind to its substrates with high specificity. In many plants and microorganisms, this enzymatic step is the gateway for nearly all sulfur that enters their metabolic systems. By doing so, it enables organisms to build the sulfur-containing compounds required for their growth and function.
The Sulfate Activation Reaction
The biochemical process catalyzed by ATP sulfurylase is a reaction involving two substrates: inorganic sulfate (SO₄²⁻) and adenosine triphosphate (ATP). The enzyme facilitates the transfer of an adenylyl group (adenosine monophosphate, or AMP) from an ATP molecule directly onto the sulfate ion. This results in the formation of two products: adenosine 5′-phosphosulfate (APS) and inorganic pyrophosphate (PPi).
The reaction can be represented as: ATP + sulfate ⇌ APS + pyrophosphate. The bond formed between the sulfate and the adenylyl group in APS is a high-energy phosphoric-sulfuric acid anhydride bond. The subsequent and rapid breakdown of PPi into two individual phosphate ions by another enzyme, inorganic pyrophosphatase, releases energy and helps to ensure the sulfate activation reaction proceeds in the forward direction.
Significance in Sulfur Metabolism
The production of adenosine 5′-phosphosulfate (APS) by ATP sulfurylase is a branching point in sulfur metabolism. The fate of APS determines which sulfur-containing compounds an organism will synthesize. In many bacteria, archaea, fungi, and plants, the primary role of APS is to serve as a substrate for two major downstream pathways.
One major pathway involves the phosphorylation of APS. An enzyme called APS kinase uses another molecule of ATP to add a phosphate group to the adenosine portion of APS, creating a molecule called 3′-phosphoadenosine-5′-phosphosulfate (PAPS). PAPS is known as the “universal sulfate donor” and is used in a wide variety of sulfation reactions, modifying proteins, lipids, and carbohydrates. The other main pathway is assimilatory sulfate reduction, where APS is directly reduced by an enzyme named APS reductase. This reduction pathway leads to the formation of sulfide, which is then incorporated into the amino acid cysteine, a precursor for methionine and other sulfur compounds like coenzyme A and biotin.
ATP Sulfurylase Across Different Life Forms
ATP sulfurylase is a ubiquitous enzyme, found in a vast array of organisms across all domains of life, though its specific purpose can differ. In bacteria, archaea, fungi, and plants, the enzyme is a foundational component of the assimilatory sulfate reduction pathway. This allows these organisms to use inorganic sulfate to synthesize their necessary sulfur-containing organic molecules like cysteine and methionine.
The situation in animals is more varied. Most animals, including humans, obtain sulfur-containing amino acids through their diet and have lost the complete assimilatory sulfate reduction pathway. However, they retain ATP sulfurylase or similar enzymes to produce PAPS. This PAPS is used in sulfonation reactions for various physiological processes, including the detoxification of drugs, the regulation of hormone activity, and modifying proteins and carbohydrates.