Simple amino acid.

Non essential amino acid.

Optically inactive due to absence of

asymetric carbon atom.

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).

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.

Glycine is synthesized from:

From Serine

From Threonine

From CO2, NH3.

From Glyoxalate.

Glycine is synthesized from serine by the

enzyme serine hydroxymethyl transferase

which is dependent on tetrahydrofolate

(THF).

SerineGlycine

Serine hydroxy methyl transferase, PLPTHFA N5,N10 methylene THF

NAD+NADH + H+

Glycine can also be obtained from threonine,

catalysed by threonine aldolase.

Threonine Glycine + acetaldehydeThreonine aldolase

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.

CO2 + NH3 Glycine

Glycine synthasecomplex, PLP

N5,N10 Methylene FH4 FH4

NAD+NADH + H+

Glycine amino transferase can catalyze the

synthesis of glycine from glyoxylate &

glutamate or alanine.

This reaction strongly favors synthesis of

glycine.

Glyoxalate Glycine

Glutamic acid α-Ketoglutarate

Glycine amino-transferase

PLP

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.

Glycine

Glycinesynthase, PLP

N5,N10 Methylene FH4FH4

NAD+NADH + H+

CO2 + NH3

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.

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

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

THFAN5,N10 methylene THF

NAD+NADH + H+

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.

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.

It is a tri-peptide, containing glutamic acid,

cysteine, glycine.

Present as reduced form (GSH) & oxidized

form (GSSG).

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

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

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

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.

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).

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.

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.

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.

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.

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.

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.

Glycine is seen where the polypeptide chain

bends or turns (beta bends or loops).

In collagen, every 3rd amino acid is 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.

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

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.

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.

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.

Textbook of Biochemistry-u Satyanarayana

Textbook of Biochemistry-DM Vasudevan