GLYCINE METABOLISM

2.  Simple amino acid.
 Non essential amino acid.
 Optically inactive due to absence of
asymetric carbon atom.

3.  Glycine is actively involved in the synthesis
of many specialized products (heme, purines,
creatine etc.
 Required for synthesis of serine & glucose.
 Involved in one-carbon metabolism.
 Glycine is the most abundant amino acid
normally excreted into urine (0.5-1.0 g/g
creatinine).

4.  Nutritional - non-essential amino acid.
 Metabolically - glucogenic amino acid.
 Glycine is one among the commonest amino
acids found in protein structure.
 Glycine is mostly present in the interior
structure of protein.
 Collagen contains very high (about 30%)
content of glycine.

6.  Glycine is synthesized from:
 From Serine
 From Threonine
 From CO2, NH3.
 From Glyoxalate.

7.  Glycine is synthesized from serine by the
enzyme serine hydroxymethyl transferase
which is dependent on tetrahydrofolate
(THF).

8. Serine
Glycine
Serine hydroxy methyl
transferase, PLPTHFA N5,N10 methylene THF
NAD+NADH + H+

9.  Glycine can also be obtained from threonine,
catalysed by threonine aldolase.
Threonine Glycine + acetaldehyde
Threonine aldolase

10.  Glycine can be synthesized by the glycine
synthase reaction from CO2, NH3 & one
carbon unit.
 This is the reversal of the glycine cleavage
system.
 It is a multienzyme complex.
 It needs the co-enzymes, NAD, lipoamide,
tetrahydrofolic acid & PLP.

11. CO2 + NH3 Glycine
Glycine synthase
complex, PLP
N5,N10 Methylene FH4 FH4
NAD+NADH + H+

12.  Glycine amino transferase can catalyze the
synthesis of glycine from glyoxylate &
glutamate or alanine.
 This reaction strongly favors synthesis of
glycine.

13. Glyoxalate Glycine
Glutamic acid α-Ketoglutarate
Glycine amino-transferase
PLP

15.  Glycine undergoes oxidative deaminaion by
glycine synthase to liberate NH4+, CO2 & one
carbon fragment as N5, N10 methylene THF.
 This provides a major route for glycine
breakdown in mammals.

16. Glycine
Glycine
synthase, PLP
N5,N10 Methylene FH4
FH4
NAD+NADH + H+
CO2 + NH3

17.  It is a multienzyme complex.
 It requires co-enzymes - PLP, NAD, THFA.
 PLP-dependent glycine decarboxylase.
 Lipoamide containing amino
methyltransferase
 Methylene THFA synthesizing enzyme.
 NAD+ dependent lipoamide dehydrogenase.

18.  Glycine is mainly channelled into the
glucogenic pathway by getting first
converted to serine.
 This is the reversal of serine hydroxy
methyltransferase reaction.
 The serine is then converted to pyruvate by
serine dehydratase

19.  Glycine is reversibly converted to serine by THF
dependent serine hydroxymethyl transferase.
 Pyruvate produced from serine by serine
dehydratase, serves as a precursor for glucose.
Glycine Serine
Serine hydroxy methyl
transferase, PLP
THFA
N5,N10 methylene THF
NAD+NADH + H+

20.  Serine is degraded to glyoxylate which
undergoes transamination to give back to
glycine.
 Glyoxylate is also converted to oxalate, an
excretory product & formate enter one
carbon pool.

21.  Formation of purine ring:
 The entire molecule of glycine is utilized for the
formation of positions 4 & 5 of carbon & position
7 of nitrogen of purines.

22.  It is a tri-peptide, containing glutamic acid,
cysteine, glycine.
 Present as reduced form (GSH) & oxidized
form (GSSG).

24.  Conjugating agent, glycine performs two
important functions.
 The bile acids - cholic acid & chenodeoxy
cholic acid- are conjugated with glycine.
Cholic acid + glycine Glycocholic acid
Chenodeoxy cholic acid + glycine Glycochenodeoxycholic acid

25.  Benzoic acid is used in small amounts as
preservative in foods.
 Glycine is used for detoxification of
benzoic acid to form hippuric acid.
Benzoic acid + glycine Hippuric acid

26.  Glycine condenses with succinyl CoA to δ-
amino levulinate which serves as a
precursor for heme synthesis.
Glycine + Succinyl CoA Amino levulinate (ALA)
ALA Synthase

27.  Creatine is present in the tissues as a high
energy compound, phosphocreatine & as free
creatine.
 Three amino acids glycine, arginine &
methionine are required for creatine formation.

28.  Step-1:
 The first reaction occurs in the mitochondria
of kidney & pancreas.
 It involves the transfer of guanidino group of
arginine to glycine, catalysed by arginine-
glycine transamidinase to produce
guanidoacetate (glycocyamine).

29.  Step-2:
 S-Adenosylmethionine (active methionine)
donates methyl group to guanidoacetate
(glycocyamine) to produce creatine.
 This reaction occurs in liver.
 Step-3:
 Creatine is reversibly phosphorylated to
phosphocreatine (creatine phosphate) by
creatine kinase.

30.  It is stored in muscle as high energy
phosphate.
 Serves as an immediate store of energy in the
muscle
 Step-4:
 The creatine phosphate may be converted to
its anhydride, creatinine.
 It is a non-enzymatic spontaneous reaction.
 Creatinine is excreted in urine.

35.  Normal serum creatinine level: 0.7 - 1.4 mg/dl.
 Serum creatine level: 0.2 - 0.4 mg/dl.
 Creatinine level in blood is a sensitive indicator
of renal function.
 In muscular dystrophies, blood creatine &
urinary creatinine are increased.
 The enzyme CK is elevated in MI.

36.  Urine level:
 Creatinine: 1 - 2 gm/day.
 Creatine: 0 - 50 mg/day.
 Creatinine coefficient:
 Males: 20 - 30 mg/kg/24hrs.
 Females: 10 - 20 mg/kg/24hrs.
 Creatinine Clearance:
 Males: 90 - 130 ml/min.
 Females: 80 - 120 ml/min.

37.  Excretion of creatinine is constant for an
individual depends on muscle mass.
 Creatinine Clearance – measure of GFR.
 Normally , urine contains – creatine (less).
 Creatinuria – increased excretion of creatine
in urine.
 Muscular dystrophy, Hypogonadism,
Hyperthyroidism, DM & Stravation.

38.  Glycine is seen in the brainstem & spinal
cord.
 Glycine opens chloride specific channels.
 In moderate levels glycine inhibits neuronal
traffic; but at high levels it causes over-
excitation.

39.  Glycine is seen where the polypeptide chain
bends or turns (beta bends or loops).
 In collagen, every 3rd amino acid is glycine.

40.  It is due to defect in glycine cleavage system.
 Glycine level is increased in blood, urine & CSF.
 Severe mental retardation & seizures are seen.
 There is no effective management.

41.  This is a rare disorder.
 Serum glycine concentration is normal, but very
high amount (normal 0.5-1 g/day) is excreted in
urine.
 It is due to defective renal reabsorption.
 It is characterized by increased tendency for
formation of oxalate renal stones.
 Urinary oxalate level is normal in these patients

42.  It is due to protein targetting defect.
 Normally, the enzyme alanine glyoxalate
amino transferase is located in peroxisomes;
but in these patients the enzyme is present in
mitochondria.
 So, enzyme is inactive.
 It characterized by increased urinary oxalate
resulting in oxalate stones.

43.  Deposition of oxalate (oxalosis) in various
tissues is observed.
 The urinary oxalate is of endogenous origin
& not due to dietary consumption of oxalate.
 Primary hyperoxaluria is due to a defect in
glycine transaminase coupled with
impairment in glyoxalate oxidation to
formate.

44.  It is a milder condition causing only
urolithiasis & results from deficient activity of
cytoplasmic glyoxalate reductase.
 The management is to increase oxalate
excretion by increased water intake.
 Minimise dietary intake of oxalates by
restricting the intake of leafy vegetables, tea,
beet-root etc.

45.  Textbook of Biochemistry-u Satyanarayana
 Textbook of Biochemistry-DM Vasudevan