AASDHPPT - L-Aminoadipate-Semialdehyde Dehydrogenase-Phosphopantetheinyl Transferase | Elisa - Clia - Antibody - Protein

Background

AASDHPPT (L-Aminoadipate-Semialdehyde Dehydrogenase-Phosphopantetheinyl Transferase) is a bifunctional enzyme involved in two distinct biochemical pathways. It combines the activities of L-aminoadipate-semialdehyde dehydrogenase and phosphopantetheinyl transferase within a single polypeptide. This enzyme plays a crucial role in lysine degradation and the activation of certain enzymes via post-translational modification. It is an enzyme quite similar to LYS5 ( Saccharomyces cerevisae) involved in the biosynthesis of lysine, an essential amino acid.Pipecolic acidemia, is a disorder related with defects with AASDHPPT gene.The ligands for AASDHPPT include: L-Aminoadipate-Semialdehyde, NAD+ (Nicotinamide Adenine Dinucleotide), Coenzyme A (CoA), The donor of the 4'-phosphopantetheinyl group for the phosphopantetheinyl transferase activity, Target Proteins (ACPs and PCPs): The acceptors of the 4'-phosphopantetheinyl group

Structural Features

AASDHPPT is characterized by its dual enzymatic domains:

• L-Aminoadipate-Semialdehyde Dehydrogenase Domain: This domain is involved in the oxidative deamination of L-aminoadipate-semialdehyde to L-aminoadipate, a key step in the lysine degradation pathway.
• Phosphopantetheinyl Transferase Domain: This domain transfers a 4'-phosphopantetheinyl group from coenzyme A to target proteins, typically acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs). This modification is essential for the activity of these carrier proteins in fatty acid synthesis, polyketide synthesis, and non-ribosomal peptide synthesis.

Subtypes and Classification

AASDHPPT is classified based on its bifunctional nature:

• Lysine Degradation Pathway Enzyme: The dehydrogenase activity places it within enzymes involved in amino acid catabolism.
• Post-Translational Modification Enzyme: The phosphopantetheinyl transferase activity categorizes it among enzymes responsible for post-translational modifications.

There are no widely recognized subtypes of AASDHPPT, but isoforms might exist due to alternative splicing or species-specific variations.

Physiological Functions

AASDHPPT has key physiological roles including:

• Lysine Degradation: By converting L-aminoadipate-semialdehyde to L-aminoadipate, it contributes to the catabolism of lysine, an essential amino acid.
• Activation of Carrier Proteins: The phosphopantetheinylation of ACPs and PCPs is crucial for the functionality of these proteins in various biosynthetic pathways, including fatty acid synthesis and secondary metabolite production.

Clinical Implications

Mutations or dysregulation of AASDHPPT can lead to clinical conditions such as:

• Pyridoxine-Dependent Epilepsy: Defects in lysine degradation can cause an accumulation of metabolites leading to neurotoxic effects.
• Metabolic Disorders: Abnormal lysine catabolism can result in metabolic imbalances affecting overall amino acid homeostasis.