EDNOS

Endothelial cell growth factor 1 (ECGF1), also known as thymidine phosphorylase, is an enzyme that in humans is encoded by the ECGF1 gene. This enzyme is involved in the pyrimidine salvage pathway, where it catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxy-D-ribose-1-phosphate.

Function

ECGF1 plays a crucial role in the regulation of angiogenesis, the process by which new blood vessels form from pre-existing vessels. This is particularly important in the context of tumor growth, wound healing, and cardiovascular diseases. The enzyme's activity is associated with the promotion of endothelial cell proliferation and migration, which are key steps in angiogenesis.

Clinical Significance

Mutations in the ECGF1 gene have been linked to mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare autosomal recessive disorder characterized by gastrointestinal dysmotility, peripheral neuropathy, and leukoencephalopathy. The deficiency of thymidine phosphorylase activity in MNGIE leads to the accumulation of thymidine and deoxyuridine, which causes mitochondrial DNA instability.

ECGF1 is also a target for cancer therapy, as its role in angiogenesis makes it a potential target for anti-angiogenic drugs. Inhibitors of thymidine phosphorylase are being investigated for their ability to suppress tumor growth by reducing the blood supply to the tumor.

Structure

The ECGF1 protein is a homodimer, meaning it consists of two identical subunits. Each subunit binds to a phosphate group and a thymidine molecule. The enzyme's active site is located at the interface of the two subunits, where the catalytic reaction takes place.

Regulation

The activity of ECGF1 is regulated by various factors, including the availability of its substrates and the presence of inhibitors. It is also subject to regulation by cytokines and growth factors that influence angiogenesis.

Research

Ongoing research is focused on understanding the detailed mechanisms by which ECGF1 contributes to angiogenesis and its potential as a therapeutic target. Studies are also exploring the role of ECGF1 in other diseases characterized by abnormal blood vessel formation.

Also see

• Angiogenesis
• Mitochondrial neurogastrointestinal encephalomyopathy
• Thymidine phosphorylase
• Pyrimidine salvage pathway