GLYCINE

BIOCHEMISTRY SEMINAR(2019)
METABOLIS
M
NAME – RUPAM RAJPUROHIT
ROLL NO. - 118
 CHEMISTRY OF GLYCINE


SIMPLE, NON-ESSENTIAL AMINO ACID.

OPTICALLY INACTIVE DUE TO ABSENCE OF CHIRAL
CARBON

MOST ABUNDANT AMINO ACID NORMALLY EXCRETED
IN URINE.
CHEMICAL FORMULA: C2H5N02

ANABOLISM
ANABOLISM
 USES OF GLYCINE

SYNTHESIS OF SPECIALISED
PRODUCTS SUCH AS
HEME,PURINES , CREATININE, ETC.
SYNTHESIS OF SERINE AND
GLUCOSE.
INVOLVED IN ONE CARBON
METABOLISM.
 • CHOLINE
• GLYOXALIC ACID
GLYOXALATE • CREATINE CREATINE PO4CREATININE
3-

• C4, C5 AND N7 OF PURINE RING

• BILE SALTS
PROTEINS • ALA > HEME

AMMONIA UREA
GLYCINE
SERINE

SERINE PYRUVATE GLUCOSE

CO2 + NH3(ONE CARBON
MET.)

OVERVIEW OF GLYCINE
 FROM SERINE
GLYCINE IS SYNTHESIZED FROM SERINE BY
THE ENZYME SERINE HYDROXYMETHYL
TRANSFERASE WHICH IS DEPENDENT ON
TETRAHYDROFOLATE.
 FROM THREONINE
GLYCINE CAN BE SYNTHESIZED FROM THREONINE
CATALYSED BY THE ENZYME THREONINE
ALDOLASE.
 FROM CO2 AND NH3
• GLYCINE CAN BE SYNTHESIZED BY THE GLYCINE
SYNTHETASE REACTION FROM CO2 AND NH3 AND ONE
CARBON UNIT.
• IT IS A MULTI ENZYME COMPLEX.
• COENZYMES REQD. – NAD, LIPOAMIDE,
TETRAHYDROFOLIC ACID & PLP.
 FROM GLYOXALATE
• GLYCINE AMINO TRANSFERASE CAN
CATALYZE THE SYNTHESIS OF GLYCINE
FROM GLYOXALATE & GLUTAMATE OR
ALANINE.
Summed up ANABOLIC processes of Glycine
Summed up ANABOLIC processes of Glycine

NADH + H+
N5,N10 METHYLENE
THF

NAD+
THF

THF N5,N10 2- GLUTAMATE ALANINE

METHYLENE OXOGLUTARAT
E
THF
PYRUVATE
ACETALDEHYDE
CATABOLISM
CATABOLISM
In
Mammals
Glycine undergoes oxidative deamination by glycine
synthase to liberate NH CO & one carbon fragment
4+,

:
as N , N methylene THF.
5 10
2
Glycine Synthetase Complex

• 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.
 GLUCOGENIC PATHWAY
• Glycine is mainly channelled into the glucogenic pathway by getti
first converted to serine.
• This is the reversal of serine hydroxy methyltransferase reaction.
• The serine is then converted to pyruvate by serine dehydratase
• 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.
• 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.

Fig. GLUCOGENIC PATHWAY

Synthesis of Specialized Products
1.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.
2. Formation of Glutathione

• It is a tri-peptide, containing glutamic acid,

cysteine, glycine.
• Present as reduced form (GSH) & oxidized form
(GSSG).
3. Formation of Heme:

• Glycine condenses with succinyl CoA to δ

amino levulinate which serves as a precursor
for heme synthesis.
4. Biosynthesis of Creatine:

• 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.
5. Conjugation Reactions:
• Conjugating agent, glycine performs two important
functions.
• The bile acids - cholic acid & chenodeoxycholic acid- are
conjugated with glycine.
• Benzoic acid is used in small amounts as
preservative in foods.
• Glycine is used for detoxification of benzoic acid to
form hippuric acid.
Metabolic Disorders of Glycine
• 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.
 GLYCINURIA
• 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.
PRIMARY HYPEROXALURIA
• It is due to protein targetting defect.
• Normally, the enzyme alanine glyoxylate 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.
• 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.
TYPE-2 PRIMARY HYPEROXALURIA
• 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.
THANK YOU