Metabolism of Glycine. .
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Glycine is the simplest amino acid that can be synthesized from serine, threonine, carbon dioxide, or glyoxylate. It is involved in the synthesis of proteins, heme, purines, creatine, glutathione, and acts as a conjugating agent. Excess glycine is excreted in urine and can lead to renal stones if accumulated. A rare disorder is glycinuria where large amounts of glycine are excreted in urine due to defective renal reabsorption. Primary hyperoxaluria is an inborn error characterized by high urinary oxalate excretion resulting from a defect in glycine transaminase.
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Metabolism of Glycine. .
- 2. COO - R group Amino group Carboxylic group Structure Glycine CH N3 + Ha H
- 3. Simplest amino acid, Non-essential amino acid, Optically inactive amino acid and glycogenic amino acid (precursor for glucose) Involve in synthesis of proteins. Actively involved in synthesis of specialized products, such as…. heme, purines, creatine Participation in one-carbon metabolism. Excessive consumption leads to renal stone.
- 4. One among the commonest amino acids found in protein structure. Being small and non-polar, glycine is mostly present in the interior structure of protein. Collagen contains very high (about 30%) content of glycine. Every 3rd amino acid in collagen is glycine.
- 6. Glycine can be synthesized from, 1. Serine 2. Threonine 3. Carbon dioxide and ammonia 4. Glyoxylate
- 8. Threonine Glycine Acetaldehyde Threonine aldolase PLP CH3-CH2-CH-COOH NH2 _ OH _ H-CH-COOH NH2 _ H – C - CH3 O =
- 10. Glycine H2O H2O2 Transaminase PLP NH2 – CH – COOH H _ O = CH – COO- Glyoxylate Glycine oxidase
- 11. Glycine may be degraded to… 1. Carbon dioxide and ammonia 2. Serine 3. Glyoxylate
- 12. Glycine THF Methylene THF Glycine SynthetasePLP NH3CO2 + NADH NAD+ Major bulk of glycine broken down through this route. Glycine Synthetase is multienzyme complex & Depends on PLP, NAD+ , lipoamide & THF for its activity.
- 14. Glyoxylate O2 H2O2 NH2 – CH – COOH H _ O = CH – COO- Glycine Glycine oxidase Formate Oxalate THF N10 Formyl THF Urine If accumulate leads to kidney stone
- 16. Synthesis of Purine ring C2 C 6 N1 N 9 N 3 7 N C5 C4 8C Glutamine Aspartate GlycineCO2 N10 Formyl THF N5 N10 Formyl THF
- 17. Synthesis of Heme Glycine ALA Synthase δ - Amino levulinic acid (ALA) + NADH NAD+ Succinyl CoA
- 18. Synthesis of Glutathione Glutamate γ - Glutamylcysteine synthase γ - Glutamylcysteine + ADP + Pi ATP Cysteine Glutathione is a tripeptide (γ-glutamyl-cysteinyl-glycine) & requires three amino acids for its formation Glutathione synthase γ – Glutamylcysteineglycine (Glutathione) ADP + Pi ATP glycine
- 19. Synthesis of Glutathione (GSH) Glutathione is a tripeptide. Widely distributed in tissues. Present in oxidized and reduced state. Functions of Glutathione Component of an antioxidant enzyme Glutathione peroxidase which is required for free radical scavenging. Maintains integrity of RBC membrane. Protect Hb from oxidation by H2O2 Transport of amino acids (Meister cycle) Detoxification Formation and stabilization of disulphide linkage in proteins. Acts as cofactor for some enzymes.
- 20. Glycine as Conjugating agent Cholic acid Glycocholic acid Glycine Benzoic acid Hippuric acid/ Benzoyl glycine
- 21. Creatine Arginine Ornithine Glycine Transamidase Creatine phosphate CreatininePi Urine Urea cycle Guanidoacetate SAM S-Adenosylhomocysteine ATP ADP H2O Creatine kinase methyltransferase
- 22. Creatine & creatinine—clinical importance The normal conc. of creatine and creatinine in human serum & urine are…. Serum Creatine — 0.2–0.6 mg/dl Creatinine — 0.6–1 mg/dl Urine Creatine — 0–50 mg/day Creatinine — 1–2 g/day Estimation of serum creatinine (along with blood urea) is used as a diagnostic test to assess kidney function. The amount of creatinine excreted is proportional to total creatine phosphate content of the body and, in turn, the muscle mass.
- 23. The daily excretion of creatinine is usually constant. Increased output of creatine in urine is referred to as creatinuria. Creatinuria is observed in muscular dystrophy, diabetes mellitus, hyperthyroidism, starvation etc.
- 25. This is a rare disorder. Serum glycine conc. is normal, but very high amount of it (normal 0.5-1 g/day) is excreted in urine. It is believed that glycinuria is due to a defective renal reabsorption.
- 26. It is an inborn error, Characterized by high urinary excretion of oxalate resulting in oxalate stones due to a defect in glycine transaminase coupled with impairment in glyoxalate oxidation to formate. Deposition of oxalate (oxalosis) in various tissues is observed. It is now known that primary hyperoxaluria is mainly due to a defect in protein targeting. As a result, the enzyme glycine transaminase is found in mitochondria instead of its normal distribution in peroxisomes.
- 27. ….