AASS - Alpha-aminoadipic semialdehyde synthase mitochondrial |Elisa - Clia - Antibody - Protein

Background

AASS (Alpha-aminoadipic semialdehyde synthase) is a mitochondrial enzyme involved in the catabolism of the essential amino acid lysine. It plays a crucial role in the pipecolic acid pathway of lysine degradation, converting lysine into alpha-aminoadipic semialdehyde, an intermediate in the pathway leading to the production of acetyl-CoA. with a size of 926 amino acids and approximately 102 kDa, plays a key role in the initial stages of L-lysine degradation in mammals through the saccharopine pathway located in the mitochondria. This pathway is considered the primary metabolic route for lysine breakdown in higher eukaryotes. In humans, this enzyme is encoded by the AASS gene and is crucial in the major lysine degradation pathway. While similar to enzymes produced by the LYS1 and LYS9 genes in yeast, it differs from the bifunctional enzyme found in plants both structurally and functionally. Mutations in the AASS gene and the alpha-aminoadipic semialdehyde synthase enzyme in humans are linked to familial hyperlysinemia, a rare inherited disorder characterized by an autosomal recessive pattern of inheritance.

Structural Features

AASS is a bifunctional enzyme composed of two distinct domains:

• Saccharopine Dehydrogenase (SDH) Domain: Responsible for the conversion of saccharopine to alpha-aminoadipic semialdehyde.
• Lysine-Ketoglutarate Reductase (LKR) Domain: Catalyzes the reduction of lysine and alpha-ketoglutarate to saccharopine.

These domains work in tandem to facilitate the stepwise degradation of lysine within the mitochondria.

Subtypes and Classification

AASS is classified based on its dual enzymatic activities within the lysine degradation pathway. There are no distinct subtypes of AASS, but alternative splicing and genetic variations can lead to different isoforms or mutations affecting its function.

Ligands

The ligands for AASS include:

• Lysine: The substrate for the lysine-ketoglutarate reductase activity.
• Alpha-Ketoglutarate: A co-substrate in the reduction reaction catalyzed by the lysine-ketoglutarate reductase domain.
• Saccharopine: An intermediate product and substrate for the saccharopine dehydrogenase activity.
• NADP+/NADPH: Coenzymes involved in the redox reactions facilitated by both enzymatic domains.

Physiological Functions

AASS is essential for:

• Lysine Catabolism: Facilitating the degradation of lysine through the pipecolic acid pathway, ultimately contributing to energy production and metabolic balance.
• Production of Metabolic Intermediates: Generating alpha-aminoadipic semialdehyde, which is further processed to produce acetyl-CoA, an important molecule in the citric acid cycle and energy metabolism.

Clinical Implications

Mutations or deficiencies in AASS can lead to metabolic disorders, primarily affecting lysine degradation:

• Hyperlysinemia: An inherited metabolic disorder characterized by elevated levels of lysine in the blood, which can lead to developmental delays, muscle weakness, and other neurological symptoms.
• Hyperlysinuria: Excess lysine in the urine, often associated with hyperlysinemia, can be indicative of a malfunction in lysine degradation.