ALAD - Delta-aminolevulinic acid dehydratase | Elisa - Clia - Antibody - Protein

Background:

ALAD or Delta-aminolevulinic acid dehydratase is an enzyme involved in the heme biosynthetic pathway, catalyzing the condensation of two molecules of delta-aminolevulinic acid (ALA) to form porphobilinogen. This reaction is the second step in the biosynthesis of heme, a crucial component of hemoglobin, myoglobin, and cytochromes. ALAD deficiency, also known as porphyria, is a rare genetic disorder characterized by reduced activity of the ALAD enzyme. This deficiency leads to the accumulation of ALA and its precursor, causing a variety of symptoms such as abdominal pain, neuropathy, and neuropsychiatric manifestations. There are two types of ALAD deficiency: acute and chronic. Acute ALAD deficiency is less common but can cause severe symptoms, while chronic ALAD deficiency typically presents with milder symptoms. The diagnosis of ALAD deficiency is often made through biochemical testing, which measures ALA and porphobilinogen levels in urine and detects elevated levels characteristic of the disorder. Treatment typically involves avoiding triggers such as certain medications, alcohol, and fasting, which can exacerbate symptoms. In some cases, heme therapy may be used to alleviate symptoms and reduce the accumulation of ALA and porphobilinogen.

Protein Structure:

• Monomer Composition: ALAD is a homooctamer, meaning it consists of eight identical subunits.
• Active Site: Each subunit contains an active site where the catalytic conversion of ALA to porphobilinogen occurs.
• Zinc Binding Sites: ALAD requires zinc ions for its enzymatic activity. These ions are critical for maintaining the structural integrity of the enzyme and facilitating catalysis.

Classification and Subtypes:

• Enzyme Class: ALAD is classified as a lyase, specifically an ALA dehydratase.
• Isoforms: There are no major subtypes or isoforms of ALAD; it is generally conserved with little variation across different tissues.

Function and Biological Significance:

• Heme Biosynthesis: ALAD is essential in the biosynthesis of heme, an important component of hemoglobin, myoglobin, cytochromes, and other hemoproteins.
• Catalytic Activity: The enzyme catalyzes the condensation of two molecules of ALA to form porphobilinogen, a crucial precursor in the heme synthesis pathway.
• Regulation: ALAD activity is regulated by the availability of its substrate, ALA, and by feedback mechanisms involving heme and other intermediates of the pathway.

Interactions:

• Substrate Interaction: ALAD specifically interacts with ALA molecules during the catalytic process.
• Metal Ions: Zinc ions are essential for ALAD’s structure and function. It can also bind other metals, which can inhibit its activity.
• Inhibitors: ALAD is susceptible to inhibition by heavy metals such as lead, which can bind to the enzyme and disrupt its function.

Clinical Issues:

• Lead Poisoning: Inhibition of ALAD by lead results in the accumulation of ALA, leading to symptoms of lead poisoning such as abdominal pain, neuropathy, and anemia.
• Porphyria: Genetic mutations in the ALAD gene can lead to a rare condition known as ALAD porphyria, characterized by abdominal pain, neuropsychiatric symptoms, and photosensitivity.
• Diagnostic Marker: Elevated levels of ALA in urine can be a diagnostic marker for lead poisoning and certain types of porphyria.

Summary:

Delta-aminolevulinic acid dehydratase (ALAD) is a vital enzyme in the heme biosynthetic pathway, converting ALA to porphobilinogen. Its activity is dependent on zinc ions and is inhibited by heavy metals like lead. ALAD is essential for the production of heme, which is crucial for various biological functions. Clinical conditions associated with ALAD dysfunction include lead poisoning and ALAD porphyria, making this enzyme significant both in normal physiology and disease states. Understanding ALAD’s structure, function, and regulation is critical for diagnosing and treating related disorders.