AK - Adenylate kinase | Elisa - Clia - Antibody - Protein

Background:

Adenylate kinase (AK) is an enzyme that plays a crucial role in cellular energy metabolism by facilitating the transfer of phosphate groups between adenine nucleotides, primarily adenosine triphosphate (ATP) and adenosine monophosphate (AMP). This transfer of phosphate groups is essential for maintaining the balance of adenine nucleotides within cells and providing energy for various cellular processes. Adenylate kinase catalyzes the reversible phosphorylation of AMP to form ATP from two molecules of ADP. This reaction allows the cell to recycle ADP, which is generated during cellular processes like muscle contraction or biosynthesis, back into ATP, the primary energy currency of the cell. Adenylate kinase is found in virtually all cells and tissues throughout the body, reflecting its fundamental role in cellular metabolism. It is particularly abundant in tissues with high energy demands, such as muscle and brain tissue. Deficiencies or dysregulation of adenylate kinase have been associated with various diseases and conditions, including muscular dystrophies, metabolic disorders, and certain cancers

Protein Structure:

Domains: AK consists of three main domains:

• CORE domain: Central region responsible for ATP binding.
• LID domain: Covers the ATP-binding site, crucial for enzyme activity.

NMPbind domain: Binds to AMP or ADP.

Isoforms: There are multiple isoforms of AK, each adapted to specific cellular locations and functions:

• AK1: Cytosolic, most abundant in muscle and brain.
• AK2: Mitochondrial intermembrane space.
• AK3: Mitochondrial matrix, specific for AMP and GTP.
• AK4, AK5, AK6, etc.: Found in various tissues with specific roles.

Classification and Subtypes:

1. Family: AK belongs to the nucleoside monophosphate (NMP) kinase family.
2. Subtypes: Based on cellular localization and substrate specificity:

• AK1: Found in the cytosol.
• AK2: Located in the mitochondrial intermembrane space.
• AK3: Present in the mitochondrial matrix.
• Other AK isoforms with specific tissue distributions and functions.

Function and Biological Significance:

• Energy Homeostasis: AK catalyzes the following reaction:
• 2ADP↔ATP+AMP

This reaction is crucial for maintaining the cellular energy balance by regulating the levels of ATP, ADP, and AMP.

• Signal Transduction: AK-generated AMP serves as a signaling molecule for various cellular pathways, including those involved in stress responses and metabolic regulation.
• Metabolic Regulation: AK activity is linked to the regulation of metabolic processes, influencing cellular responses to energy demands and nutrient availability.

Interactions:

• Metabolic Enzymes: AK interacts with various enzymes in the glycolytic and oxidative phosphorylation pathways, facilitating efficient energy transfer.
• Mitochondrial Proteins: Isoforms like AK2 and AK3 interact with mitochondrial proteins to regulate ATP synthesis and transport.
• AMP-Activated Protein Kinase (AMPK): AMP produced by AK activates AMPK, a key regulator of cellular energy homeostasis.

Clinical Issues:

• Inherited Deficiencies: Mutations in AK genes can lead to metabolic disorders. For example, AK2 deficiency is associated with reticular dysgenesis, a severe form of combined immunodeficiency.
• Cancer: Dysregulated AK activity has been linked to altered energy metabolism in cancer cells, contributing to tumor growth and survival.
• Cardiovascular Diseases: Abnormal AK activity can affect heart muscle function, influencing conditions like ischemia and heart failure.

Summary:

Adenylate kinase (AK) is a pivotal enzyme in cellular energy management, catalyzing the interconversion of adenine nucleotides (ATP, ADP, AMP) to maintain energy balance. AK is present in multiple isoforms, each adapted to specific cellular compartments and roles, from the cytosol to various mitochondrial locales. Its functions extend beyond energy metabolism to include roles in signal transduction and metabolic regulation. Clinical implications of AK range from metabolic and immune disorders to cancer and cardiovascular diseases, underscoring its broad biological significance and potential as a therapeutic target.