Glycine decarboxylase, also known as glycine dehydrogenase, is an enzyme that breaks down the amino acid glycine. This protein is part of a larger enzymatic group operating inside mitochondria. Its function is to regulate glycine levels, supporting the normal function and development of nerve cells, as glycine is both a protein building block and a brain chemical messenger. This process is a part of metabolism in animals, plants, and bacteria.
The Glycine Cleavage System
Glycine decarboxylase (GDC) is a component of a multi-enzyme group called the Glycine Cleavage System (GCS), which is found on the inner membrane of mitochondria. The GCS consists of four proteins working in a coordinated sequence: the P-protein, T-protein, H-protein, and L-protein. GDC is the P-protein in this assembly.
The components of the GCS each have a specialized task. The P-protein (GDC) initiates the process by binding to glycine and releasing a molecule of carbon dioxide. The H-protein acts as a shuttle, carrying the remaining aminomethyl group from the P-protein to the T-protein. The T-protein then catalyzes a reaction with tetrahydrofolate to release ammonia and form 5,10-methylenetetrahydrofolate.
Finally, the L-protein, a lipoamide dehydrogenase, concludes the cycle by regenerating the H-protein for another round of glycine breakdown. The overall reaction converts glycine into carbon dioxide, ammonia, and a one-carbon unit carried by tetrahydrofolate.
Role in Plant Photorespiration
In many plants, glycine decarboxylase is part of a metabolic pathway called photorespiration. This process occurs when the enzyme RuBisCO mistakenly fixes oxygen instead of carbon dioxide, creating a toxic byproduct. Photorespiration acts as a salvage pathway to recycle this byproduct and recover carbon that would otherwise be lost.
During photorespiration, the byproduct is converted into glycine and transported into the mitochondria. There, the Glycine Cleavage System breaks down two molecules of glycine. This reaction releases a molecule of carbon dioxide that can re-enter the Calvin cycle for photosynthesis. The process also generates ammonia and the amino acid serine, which can be converted into other useful molecules.
The high rate of this pathway requires large quantities of GCS proteins in plant leaf mitochondria. In some plants, these enzymes can make up over 30% of the total protein in the mitochondrial matrix. This abundance highlights the role of the GCS in mitigating the inefficiencies of photosynthesis and maintaining metabolic balance.
Function in Animal Metabolism
In animals, the Glycine Cleavage System manages amino acid levels and supports metabolic processes. Its primary role is the catabolism of excess glycine from diet or protein turnover. This breakdown prevents the accumulation of glycine to potentially toxic levels, which is important for the central nervous system.
The breakdown of glycine by the GCS yields products for other metabolic pathways. The released ammonia is processed through the urea cycle, and the carbon dioxide is exhaled. The one-carbon unit transferred to tetrahydrofolate (a folate derivative) is also a product. This molecule, 5,10-methylenetetrahydrofolate, donates methyl groups for synthesizing other compounds.
These one-carbon units are used to create purines, the building blocks for DNA and RNA. They are also necessary for synthesizing other amino acids, such as methionine. By supplying these fragments, the Glycine Cleavage System connects glycine breakdown to the production of genetic material and other proteins.
Glycine Encephalopathy
A non-functioning Glycine Cleavage System can lead to a rare genetic disorder called Glycine Encephalopathy, or Nonketotic Hyperglycinemia (NKH). This condition results from an inability to break down glycine, causing it to accumulate in tissues, especially the brain and cerebrospinal fluid. This buildup is toxic to the nervous system and leads to neurological problems.
The most frequent cause of NKH is a mutation in the GLDC gene, which provides instructions for making the glycine decarboxylase enzyme (P-protein). Over 400 different mutations in this gene account for more than 80% of NKH cases. These genetic changes can result in a nonfunctional enzyme or one with reduced activity, impairing the entire Glycine Cleavage System.
NKH becomes apparent shortly after birth with several symptoms. Affected infants often experience developmental delays and epilepsy due to glycine buildup in the brain. Common symptoms include:
- Lethargy
- Breathing difficulties
- Low muscle tone (hypotonia)
- Seizures