Argininosuccinate synthase: Difference between revisions

Latest revision as of 19:00, 23 March 2025

Argininosuccinate Synthase[edit]

Argininosuccinate synthase is an enzyme that plays a crucial role in the urea cycle, which is essential for the detoxification of ammonia in the liver. This enzyme catalyzes the condensation of citrulline and aspartate to form argininosuccinate, a key step in the conversion of ammonia to urea.

Structure[edit]

Argininosuccinate synthase is a homotetramer, meaning it is composed of four identical subunits. Each subunit contributes to the formation of the active site where the catalytic reaction occurs. The enzyme is encoded by the ASS1 gene in humans.

Function[edit]

The primary function of argininosuccinate synthase is to catalyze the reaction between citrulline and aspartate, producing argininosuccinate. This reaction is ATP-dependent and is a critical step in the urea cycle, which converts toxic ammonia into urea for excretion from the body.

Mechanism[edit]

The enzyme binds ATP and citrulline to form a citrullyl-AMP intermediate. Aspartate then attacks this intermediate, resulting in the formation of argininosuccinate and the release of AMP. This reaction is crucial for the continuation of the urea cycle.

Clinical Significance[edit]

Deficiencies in argininosuccinate synthase can lead to a disorder known as citrullinemia, which is characterized by elevated levels of citrulline in the blood. This condition can result in severe neurological impairment if not treated promptly. Management typically involves dietary restrictions and supplementation with arginine.

Related Enzymes[edit]

Argininosuccinate synthase works in conjunction with other enzymes in the urea cycle, including ornithine transcarbamylase, argininosuccinate lyase, and arginase. These enzymes collectively facilitate the conversion of ammonia to urea.

Related Pages[edit]

External Links[edit]

Template:Urea cycle

@@ Line 1: / Line 1: @@
-'''Argininosuccinate Synthase''' is an enzyme that plays a crucial role in the [[urea cycle]], a series of biochemical reactions in [[mammals]] that leads to the disposal of [[ammonia]] in the form of [[urea]]. This enzyme is encoded by the ASS1 gene in humans. Argininosuccinate synthase catalyzes the ligation of [[citrulline]] and aspartate to form argininosuccinate, an essential step in the urea cycle for the detoxification of ammonia and the production of urea.
+== Argininosuccinate Synthase ==
+[[File:Human_Argininosuccinate_Synthetase_tetramer_PDB_2NZ2.png|thumb|right|Human Argininosuccinate Synthetase tetramer]]
+'''Argininosuccinate synthase''' is an enzyme that plays a crucial role in the [[urea cycle]], which is essential for the detoxification of ammonia in the liver. This enzyme catalyzes the condensation of [[citrulline]] and [[aspartate]] to form [[argininosuccinate]], a key step in the conversion of ammonia to urea.
+== Structure ==
+Argininosuccinate synthase is a homotetramer, meaning it is composed of four identical subunits. Each subunit contributes to the formation of the active site where the catalytic reaction occurs. The enzyme is encoded by the ASS1 gene in humans.
+[[File:Active_site_of_Thermus_thermophilus_argininosuccinate_synthetase_01.png|thumb|left|Active site of Thermus thermophilus argininosuccinate synthetase]]
 == Function ==
-Argininosuccinate synthase facilitates a key reaction in the urea cycle, which is vital for the removal of toxic ammonia from the body. The enzyme catalyzes the ATP-dependent condensation of citrulline and aspartate to produce argininosuccinate. This reaction is crucial for the synthesis of [[arginine]], a precursor for the synthesis of urea, the primary vehicle for nitrogen excretion in mammals. The activity of argininosuccinate synthase is essential for maintaining the flow of nitrogen into the urea cycle, thereby preventing the accumulation of ammonia, a substance that is highly toxic to the central nervous system.
-== Structure ==
+The primary function of argininosuccinate synthase is to catalyze the reaction between citrulline and aspartate, producing argininosuccinate. This reaction is ATP-dependent and is a critical step in the urea cycle, which converts toxic ammonia into urea for excretion from the body.
-The structure of argininosuccinate synthase is well-conserved across different species, indicating its importance in metabolic processes. The enzyme is a tetramer, composed of four identical subunits. Each subunit contains an active site where the synthesis of argininosuccinate occurs. The structure of the enzyme allows for the efficient binding of substrates (citrulline and aspartate) and the necessary cofactor (ATP), facilitating the catalytic reaction.
+== Mechanism ==
+The enzyme binds ATP and citrulline to form a citrullyl-AMP intermediate. Aspartate then attacks this intermediate, resulting in the formation of argininosuccinate and the release of AMP. This reaction is crucial for the continuation of the urea cycle.
 == Clinical Significance ==
-Mutations in the ASS1 gene, which encodes argininosuccinate synthase, can lead to a rare but serious disorder known as [[argininosuccinic aciduria]]. This condition is characterized by a deficiency in the enzyme, resulting in the accumulation of ammonia and argininosuccinic acid in the blood. Symptoms of argininosuccinic aciduria include vomiting, lethargy, seizures, and cognitive impairment. Early diagnosis and treatment are critical for managing the symptoms and preventing long-term damage.
-== Genetic Regulation ==
+Deficiencies in argininosuccinate synthase can lead to a disorder known as [[citrullinemia]], which is characterized by elevated levels of citrulline in the blood. This condition can result in severe neurological impairment if not treated promptly. Management typically involves dietary restrictions and supplementation with arginine.
-The expression of the ASS1 gene is tightly regulated by various metabolic signals. Nutritional status, hormones, and other factors can influence the expression levels of argininosuccinate synthase, thereby adjusting the activity of the urea cycle according to the body's needs. Understanding the regulation of ASS1 gene expression is important for elucidating the pathogenesis of related disorders and developing targeted therapies.
+== Related Enzymes ==
+Argininosuccinate synthase works in conjunction with other enzymes in the urea cycle, including [[ornithine transcarbamylase]], [[argininosuccinate lyase]], and [[arginase]]. These enzymes collectively facilitate the conversion of ammonia to urea.
+== Related Pages ==
+* [[Urea cycle]]
+* [[Citrullinemia]]
+* [[Ornithine transcarbamylase]]
+* [[Argininosuccinate lyase]]
+* [[Arginase]]
+[[File:Citrulline_metabolism.png|thumb|right|Citrulline metabolism]]
+== External Links ==
+* [https://www.ncbi.nlm.nih.gov/gene/445 ASS1 gene - NCBI]
+* [https://www.omim.org/entry/107950 OMIM Entry on Argininosuccinate Synthase]
-== Research and Therapeutic Applications ==
+{{Enzymes}}
-Research on argininosuccinate synthase has implications for the treatment of urea cycle disorders and other conditions associated with nitrogen metabolism. Gene therapy approaches aiming to correct ASS1 gene mutations or enhance the expression of argininosuccinate synthase are under investigation. Additionally, understanding the enzyme's structure and function can aid in the design of drugs that modulate its activity, potentially offering new treatments for diseases related to nitrogen imbalance.
+{{Urea cycle}}
 [[Category:Enzymes]]
+[[Category:Urea cycle]]
 [[Category:Metabolism]]
-[[Category:Genetics]]
-{{medicine-stub}}