Glycine

Major inhibitory neurotransmitter

I- Synthesis
Glycine is a nonessential amino acid.
It is synthesized
a- From serine by serine hydroxymethyl transferase.
b- By reversal of the Glycine cleavage system.
c- By transamination from glyoxylate.
II- Catabolic Fate
Glycine is catabolized by one or more of the following pathways:
a- By glycine cleavage system (mainly), it joins the one carbon unit metabolism
through formation of methylene-tetrahydrofolate (methylene-THF).
b- Glycine may be deaminated by glycine oxidase forming glyoxylic acid.
Glyoxylic acid is converted to formic acid by oxidative-decarboxylation or
reaminated to glycine.
c- It is converted to serine by serine serine-hydroxymethyl transferase. So,
glycine is a glucogenic amino acid being converted to serine and then by
serine dehydratase into pyruvic acid, then to Glucose via gluconeogenesis.
III- Metabolic Functions and Derivatives of Glycine
1- Glycine is an essential component of some proteins e.g. collagen.
2- Glycine is a major inhibitory neurotransmitter (in moderate
levels); has inhibitory effects on the neuron; decrease the likelihood that
the neuron will fire an action potential but in high levels it causes
overexcitation.
3- Serine synthesis: by the reversible reaction catalyzed by serine
hydroxymethyl transferase.
4- Purine synthesis.
5- Glutathione biosynthesis: glutathione is γ-glutamylcysteinylglycine.
6- Creatine biosynthesis: Three amino acids, glycine, arginine and
methionine, are involved in the biosynthesis of creatine (explained later).
7- Heme biosynthesis.
8- Bile salts formation: In the liver, glycine conjugates with bile acids and
excreted in the form of bile salts. Conjugation with glycine makes these
structures more amphipathic to help emulsification of fat in the intestine.
9- It gives formyl-THF, which joins the metabolism of one carbon unit
(see folate metabolism later).
10- Glycine betaine is a methyl donor. It is formed from choline.
N.B Choline is a common component of the diet but also can be
synthesized in the human as part of the pathway for the synthesis of
phospholipids.

IV-Metabolic Disorders of Glycine

1- Primary hyperoxaluria:
Cause: genetic deficiency of the enzymes that metabolize glyoxylate
(glyoxalate aminotransferase).
Metabolic causes of manifestations: Glyoxylate is converted to oxalate
which is excreted in urine as calcium oxalate (envelop shape crystals). It
presents with increased oxalate crystals in urine. Oxaluria may be complicated
by stone formation in the urinary tract.

2- Hyperglycinemia:
Cause: deficient glycine catabolism due to lack of glycine cleavage system.
Lab findings: High glycine levels in blood, urine and CSF.
Metabolic causes of manifestations: It is associated with severe mental
retardation and seizures.
3- Glycinuria:
Cause: failure of renal tubular reabsorption of glycine leading to excess
excretion of glycine in urine.
Metabolic causes of manifestations: It is associated with oxalate stones
without hyperoxaluria because of entrapping of glycine in renal tubular cells
 that undergoes oxidation, in situ, into oxalate that precipitates stone formation
in renal parenchyma (tubular nephrocalcinosis).

Metabolism of Hydroxyl Containing Amino Acid

Serine

Serine
I- Synthesis
It is a nonessential amino acid being synthesized from:
1- Glycine by hydroxymethyl transferase.
2- 3-phosphoglycerate (of glycolysis) that undergoes oxidation to phosphohydroxy
pyruvate. The latter is aminated (by transamination) to form phosphoserine.
Phosphatase release inorganic phosphate from phosphoserine to give rise to serine.

II- Catabolic Fate

Serine is a glucogenic amino acid. It is deaminated by serine dehydratase, and
pyruvate is formed.
III- Metabolic Derivatives of Serine
1- The hydroxyl group of serine performs covalent modification of protein:
a- Phosphorylation and dephosphorylation to make the protein active or inactive as
in some enzymes.
b- Glycosylation of some proteins.
2- Synthesis of glycine and provides the carbon skeleton of cysteine.
3- Serine plays an important role in phospholipid metabolism:
a- Synthesis of phosphatidyl serine.
b- Decarboxylation of serine into ethanolamine, then, phosphatidyl ethanolamine
synthesis.
c- Methylation of ethanolamine into choline. Choline is then, utilized for: synthesis
of phosphatidyl choline (lecithin), plasmalogen and sphingomyelin.
d- Sphingosine synthesis by condensation of serine with palmitoyl CoA.
Sphingosine is then, used for sphingolipid building up.