Dr. Saidunnisa M.D

Associate ProfessorDepartment of Biochemistry

Glycine Metabolism

Oxalate stones

Learning objectives

• At the end of the session the student shall be able to :

1. Explain the major and minor pathways of glycine metabolism

2. Specialized products formed from the glycine metabolism

3. Disorders of Glycine metabolism4. Synthesis of glutathione and creatinine

Glycine Metabolism

• Is the simplest amino-acid.

• Is a non-essential amino acid.

• Optically Inactive.• Is a glycogenic amino

acid.• Forms many biologically

important compounds in the body.

Synthesis

• Major pathway for the synthesis is from serine.• Enzyme involved is serine Hydroxy methyl

transferase.• Coenzymes are THF (B12) and PLP(B6).

• Reversible reaction.• Alpha carbon of serine becomes alpha carbon of

Glycine.• Beta carbon of serine is channeled into one carbon

pool carried by THF.

Major pathway

Mechanism of Reaction

• Minor pathway for the synthesis is from Threonine.

• Enzyme involved is Threonine Aldolase.• Threonine undergoes degradation to produce

Glycine and Acetaldehyde.

Minor pathway

Degradation

• Major catabolic pathway is through oxidative deamination.

• Enzyme involved is Glycine synthase (Glycine cleavage system).

• Is a multi enzyme complex.• Coenzymes are PLP, NAD, THF.• Reversible reaction.• Products formed are CO2,NH4 and N5,N10

methylene THF.

Metabolic Pathway

• Minor catabolic pathway is through conversion to glyoxylate which is oxidized to oxalic acid is medically important.

• Oxalic acid is sparingly soluble and tends to precipitate in kidney tubules , leading to kidney stone formation (Nehrocalcinosis).

• Amino acid Glycine is a source of oxalic acid in the body.

• Glyoxylate can be transaminated back to Glycine by the enzyme Glycine transaminase .

Inherited Disorders

• Primary Hyperoxaluria: Excessive formation of oxalic acid.

• Defect: Glycine transaminase deficiency.• which can converts oxalate to Glycine leads

excessive deposition of oxalic acid in the kidney leading to Nehrocalcinosis and recurrent UTI and ultimately leading to renal failure and death.

Oxalate stones

Glycinuria

• This disease is characterized by excess urinary excretion of Glycine.

• Inheritance: Autosomal dominant• Defect: due to defect in renal tubular

reabsorption of Glycine.• Clinically : tendency to form oxalate stones in

the kidney.

Metabolic role of Glycine

1. Formation of purine ring: The entire molecule of Glycine is utilized for the formation of positions 4,5 of carbons and position 7 of nitrogen.

2. Synthesis of Heme: Glycine is necessary in the first reaction of Heme synthesis.

• Glycine condenses with succinyl CoA to form delta amino levulinate which is a precursor of heme synthesis.

collagen3. Source of formate and oxalate

for one carbon metabolism.4.It is glycogenic because

Glycine is converted to serine which is again converted to pyruvic acid.

5.Glycine being non-polar and small it is present in the turns or bends of the beta helix of protein structure.

6. Collagen contains very high glycine content.

7. Conjugation: As a conjugating agent it performs two important reactions

1. The bile acids: cholic and cheno deoxy cholic acids are conjugating with Glycine.

Cholic acid+Glycine ---Glycocholic acid

Chenodeoxy cholic acid+Glycine---Glycochenodeoxy cholic acid

2. Detoxification of benzoic acid: to hippuric acid

8. Synthesis of Glutathione: Is a tripeptide formed from 3 amino acids Glutamic acid, cysteine and Glycine

9.Synthesis of Creatine: Three amino acids are required Arginine, methionine and Glycine.