Question:The glycine cleavage system is a group of four enzymes that together catalyze the following reaction:

$\mathbf{glycine}\mathbf{+}\mathbf{}\mathbf{THF}\mathbf{}\stackrel{\mathbf{glycine}\mathbf{}\mathbf{cleavage}\mathbf{}\mathbf{system}\mathbf{}}{\mathbf{\to }}{\mathbf{N}}^{\mathbf{5}}\mathbf{}\mathbf{,}{\mathbf{N}}^{\mathbf{10}}\mathbf{}\mathbf{-}\mathbf{methylene}\mathbf{}\mathbf{-}\mathbf{}\mathbf{THF}\mathbf{}\mathbf{+}{\mathbf{CO}}_{\mathbf{2}}$

Use the following information to determine the sequence of reactions carried out by the glycine cleavage system:

a. The first enzyme is a PLP-requiring decarboxylase.

b. The second enzyme is aminomethyltransferase. This enzyme has a lipoate coenzyme.

c. The third enzyme synthesizes N⁶,N¹⁰-methylene-THF and also forms NH₄

d. The fourth enzyme is an FAD-requiring enzyme.

e.The cleavage system also requires NAD.

Glycine cleavage consists of four enzymes which are glycine decarboxylase, aminomethyl transferase, dihydrolipoyl dehydrogenase and a carrier protein. In the first reaction, glycine undergoes transamination reaction using Pyridoxal phosphate. The enzyme used here is glycine decarboxylase. Carbon dioxide gets eliminated.

3-methyl-1,2-dithiolane attacks on the double bond between carbon and nitrogen. There occurs the transamination reaction using second enzyme, i.e. aminomethyl transferase. Thus it forms 4-aminomethylsulfanyl butane-2-thiol. This is shown below:

The obtained product is treated with tetrahydrofuran using dihydrolipoyl dehydrogenase forming butane-1,3-dithiol, ammonium ion and methylene-tetrahydrofolate. It is shown below:

Butane-1,3-dithiol is treated with FAD,flavin adenine dinucleotide,using the fourth enzyme called carrier protein. It produces 3-methyl-1,2-dithiolane and FADH₂ which is then treated with NAD producing FAD, NADH and a proton.

So the complete mechanism is shown below:

So the sequence of reactions carried out by the glycine cleavage system is shown.