Fructosamine-3-kinase-Prevents the accumulation of early glycation products

Fructosamine-3-kinase (FN3K, Fructosamine-3-kinase) is an enzymeEnzymes are proteins that accelerate chemical reactions in the body. They ensure the occurrence of metabolic processes such as food digestion, energy release, cell formation, and many others. that plays an important role in the metabolism of glycated proteinsProteins are high-molecular organic substances consisting of alpha-amino acids linked in a chain by a peptide bond. In living organisms, the amino acid composition of proteins is determined by the genetic code. During synthesis, 20 standard amino acids are used in most cases. Many combinations of them determine the great diversity of properties of protein molecules. Proteins play a key role in the immune response and can perform transport, storage, catalytic, structural, and receptor functions. Proteins are an important part of the nutrition of animals and humans. The main sources of proteins are meat, poultry, fish, milk, nuts, legumes, and grains.. It catalyzes the phosphorylation of fructosamines (early glycation products), which leads to their destabilization and subsequent decomposition. This mechanism helps the body get rid of potentially harmful glycation products that can accumulate when blood sugar levels are elevated, such as in diabetes.

Structure and function of fructosamine-3-kinase

Fructosamine-3-kinase belongs to the kinase family and uses ATP (adenosine triphosphate) as an energy source for phosphorylation. The enzyme was first discovered in the 1990s, and its main function is to prevent the accumulation of early glycation products.

Mechanism of action

1. Substrates:
   • The main substrates of FN3K are fructosamines — products of nonenzymatic glycation of proteins. For example, glycated lysineLysine is an essential amino acid that is one of the main components of protein molecules with pronounced basic properties. In DNA, it is encoded by the sequences AAA and AAG. It is the foundation that makes up protein — the building material for the body's cells and tissues.  The body cannot produce lysine on its own; the amino acid enters it with food or through taking special supplements. or glycated albuminOne of the main proteins of the human body, responsible for maintaining normal blood composition and transporting various substances throughout the body. It also serves as a reserve source of amino acids. Albumins perform two very important functions: managing the distribution of water within the body, helping the blood transport vitamins, minerals, and medications. They are responsible for water exchange — they help retain it in the vessels and prevent it from excessively moving into the tissues (thus preventing the development of edema). Albumins influence the formation of tissue fluid, urine, and lymph, and also control the process of water absorption from the intestines..
   • Fructosamines are formed in the early stages of glycation when sugars (such as glucose) bind to amino groups of proteins.
2. Phosphorylation:
   • FN3K transfers the phosphate group from ATP to the third carbon atom of fructosamine, forming fructosamine-3-phosphate.
   • This phosphorylation makes the fructosamine molecule unstable.
3. Degradation of fructosamines:
   • After phosphorylation, fructosamine-3-phosphate spontaneously breaks down into the parent protein and 3-deoxyglucosone (3-DG), a reactive compound that can be further metabolized or eliminated from the body.

Role of fructosamine-3-kinase in the body

FN3K plays an important role in protecting cells from damage caused by glycation. Its main functions include:

1. Preventing the accumulation of early glycation products:
   • FN3K helps remove fructosamines before they turn into more stable and harmful glycation end products (AGEs).
2. Protein protection:
   • Glycation can disrupt the structure and function of proteins. FN3K helps maintain the normal function of proteins, preventing their damage.
3. Regulation of glucose metabolism:
   • FN3K is involved in maintaining glucose homeostasis by preventing the accumulation of glycated proteins that can disrupt cellular processes.

Fructosamine-3-kinase expression

FN3K is expressed in a variety of tissues, including:

• Liver: The main organ where glucose metabolism and detoxification takes place.
• Kidneys: They are involved in the elimination of decay products.
• Red blood cells: Blood cells that frequently undergo glycation due to high glucose levels.
• Brain: Protecting neurons from damage caused by glycation.

FN3K Genetics

The gene encoding fructosamine-3-kinase is located on chromosome 17 (17q25. 3). There are several known polymorphisms of this gene that can affect the activity of the enzyme. For example, some gene variants are associated with an increased risk of diabetic complications.

Clinical significance of fructosamine-3-kinase

1. Diabetes:
   • In diabetes, blood glucose levels are elevated, leading to increased protein glycation. FN3K helps lower fructosamine levels, which can slow the development of complications such as diabetic nephropathy, retinopathy, and neuropathy.
2. Biomarkers:
   • The level of fructosamines in the blood is used as a marker of the average glucose level over the past 2-3 weeks. FN3K activity can affect this indicator.
3. Aging:
   • With age, FN3K activity may decrease, which contributes to the accumulation of AGEs and aging of tissues.
4. Neurodegenerative diseases:
   • Glycation of proteins in the brain is associated with the development of Alzheimer’s and Parkinson’s diseases. FN3K can play a protective role by preventing the accumulation of glycated proteins.

Therapeutic potential of FN3K

Research suggests that increasing FN3K activity may be beneficial in preventing glycation-related complications. Some approaches include:

1. FN3K Activators:
   • Developing drugs that increase the enzyme’s activity can help reduce fructosamine and AGEs levels.
2. Gene therapy:
   • The introduction of additional copies of the FN3K gene can increase the activity of the enzyme in tissues.
3. Antioxidants:
   • Since oxidative stress increases glycation, antioxidants may indirectly support FN3K function.

Conclusion

Fructosamine-3-kinase is an important enzyme that protects the body from damage caused by protein glycation. Its role in fructosamine metabolism makes it a key player in preventing complications of diabetes, aging, and neurodegenerative diseases. The study of FN3K opens up new possibilities for developing therapeutic strategies aimed at combating the effects of glycation.