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

7. Serine
Glycine
Methylene
THF
THF
Serine Hydroxymethyl
Transferase
PLP
NH2-CH-COOH
CH2OH
_
NH2-CH-COOH
H
_

8. Threonine
Glycine
Acetaldehyde
Threonine aldolase
PLP
CH3-CH2-CH-COOH
NH2
_
OH
_
H-CH-COOH
NH2
_
H – C - CH3
O
=

9. Glycine
THF
Methylene
THF
Glycine SynthetasePLP
NH3
NH2-CH-COOH
H
_
CO2 +
NADH
NAD+

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.

13. Glycine
Serine
THF
Methylene
THF Serine Hydroxymethyl
TransferasePLP
NH2-CH-COOH
CH2OH
_
NH2-CH-COOH
H
_
Pyruvate
CH3-C-COOH
O
=
Glucose
Serine
dehydratase

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. ….