DEGRADATION OF

NON ESSENTIAL
AMINO ACIDS
GROUP 3
INTRODUCTION
DEGRADATION
 SERINE
Serine is a non-essential amino acid.
Synthesis of Serine: Serine is synthesized from glycine by transfer of
hydroxymethyl group from N5 N10-methylene THF(tetrahydrafolate).

Catabolism of Serine: In humans, serine is catabolized via glycine

and N5 , N10-methylene tetrahydrofolate. The reaction is catalyzed by
serine hydroxy methyl transferase . Further catabolism of serine
merges with that of glycine.
In many mammals, serine is degraded by serine dehydratase, an
enzyme that requires pyridoxal phosphate (PLP) and produces NH4 +
and pyruvate. This pathway appears to be a minor one in humans.
IMPORTANCE OF SERINE

• Serine is a constituent of phospholipid, phosphstidylserine, found in brain.

• After decarboxylation serine give rise to ethanolamine which is the constituent of another
phospholipid, phosphatidylethanolamine (cephalin).
• Serine also takes part in the synthesis of cysteine
ALANINE
Alanine is a nonessential amino acid.
Synthesis and Catabolism of Alanine: It is produced from pyruvate by a transamination
reaction catalyzed by alanine transaminase (ALT) and may be metabolized back to pyruvate
by a reversal of the same reaction.
Alanine is a major glucogenic amino acid.
IMPORTANCE OF ALANINE

• In fasting, alanine plays a key role in hepatic gluconeogenesis.

• Alanine is released from muscle (for the transport of ammonia to the liver) during fasting
and undergoes transamination to form pyruvate.
• The pyruvate is then converted to glucose by the gluconeogenesis.
• Thus, alanine has an important role in maintaining the fasting blood glucose level by way
of gluconeogenesis.
 GLUTAMIC ACID
Glutamic acid is a nonessential, glucogenic amino acid.
Synthesis of Glutamic Acid: It is synthesized from α-
ketoglutarate an intermediate of citric acid cycle by:
• Transamination
• By reductive amination of a ketoglutarate by NH4 +,
catalyzed by glutamate dehydrogenase.
Catabolism of Glutamic Acid: When glutamate is
degraded, it is converted back to α-ketoglutarate either by
transamination or by glutamate dehydrogenase reaction.
IMPORTANCE OF GLUTAMIC ACID

• A number of other amino acids like glutamine, proline and arginine are derived from
glutamate.
• Glutamate involved in the synthesis of glutathione, (γ-glutamyl-cysteinyl glycine) which
is involved in the reduction of H2O2 to H2O and transport of amino acids into cells of
kidney and intestine.
• Glutamate is decarboxylated at C-1 to form amine gamma aminobutyric acid (GABA),
which serves as a neurotransmitter.
GLUTAMINE
Glutamine is an amide of glutamate.
Synthesis of Glutamine: It is produced from
glutamate by glutamine synthetase, which
adds NH4 + to the carboxyl group of the side
chain, forming an amide.
Degradation of Glutamine: Glutamine is
reconverted to glutamate by a different
enzyme, glutaminase, which is particularly
important in the kidney.
IMPORTANCE OF GLUTAMINE

• Glutamine is the major transport form of ammonia.

• Glutamine is the principal source of ammonia in the kidney, the ammonia it produces
enters the urine and decreases its acidity (NH3 + H+ → NH4 + ) and in this way it plays
an important role in the maintenance of acid-base balance.
• Glutamine participates in a number of biosynthetic reactions, usually by supplying amino
or ammonia nitrogen, e.g. in the formation of arginine, carbamoyl phosphate, purines, etc.
ASPARTIC ACID
Aspartic acid is a nonessential, glucogenic amino acid.
Synthesis of Aspartic Acid: Aspartate is synthesized from Kreb’s citric acid cycle
intermediate, oxaloacetate by transamination reaction.
Degradation of Aspartic Acid: Because the transamination reaction is readily reversible,
aspartate can be converted to oxaloacetate, an intermediate of citric acid cycle
IMPORTANCE OF ASPARTIC ACID

• • In the urea cycle, aspartate reacts with citrulline to form arginosuccinate, which is
cleaved, forming an essential amino acid arginine and fumarate.
• Aspartate reacts with inosine monophosphate (IMP) to form AMP (Adenosine
monophosphate).
ASPARGINE
Aspargine is an amide of aspartate.
Synthesis of Aspargine: Aspargine is formed
from aspartate by a reaction in which
glutamine provides the nitrogen for formation
of the amide group.
Degradation of Aspargine: Hydrolytic release
of the amide nitrogen of aspargine as ammonia
and aspartate is catalyzed by asparginase.
IMPORTANCE OF ASPARGINE

• Certain types of tumor cells, particularly leukemic cells, require aspargine. Therefore,
asparginase has been used as an antitumor agent.
• It acts by converting aspargine to aspartate, decreasing the amount of aspargine available
for tumor cell growth.
 CYSTEINE
Cysteine is a nutritionally non-essential, glucogenic amino acid.
Synthesis: It is synthesized from two amino acids, methionine, which is nutritionally
essential and serine, which is not. Methionine furnishes sulfur atom and serine furnishes the
carbon skeleton. Cystine is formed by oxidation of cysteine.
Catabolism of Cystine and Cysteine: The major catabolic fate of cystine is conversion of
cystine to cysteine a reaction catalyzed by cystine reductase. Catabolism of cystine then
occurs simultaneously with that of cysteine.
Cysteine can be catabolized by two routes as follows:
1. The transamination pathway
2. Direct oxidative pathway
 THE TRANSAMINATION PATHWAY

• One principal pathway is its transamination in the presence of α-ketoglutarate

by the enzyme cysteine transaminase to form β-mercaptopyruvate and
glutamate.
• β-Mercaptopyruvate then undergoes desulfuration with sulfur transferase to
form pyruvate and H2S, which is converted to sulfide by reduced glutathione.
• The sulfide formed in the reaction is converted to sulfite and then to sulfate
(SO4 – –).
• The sulfate thus formed is either excreted in the urine or converted to active
sulfate, phosphoadenosyl phosphosulfate (PAPS) by using ATP. PAPS is used
as a source of sulfur in the synthesis of polysaccharides, glycolipids and
sulpholipids or used for detoxification reactions.
DIRECT OXIDATIVE PATHWAY

• Cysteine is oxidized to cysteine sulfinate by cysteine dioxygenase which is then

decarboxylated to hypotaurine. Hypotaurine may be oxidized to taurine (an inhibitory
neurotransmitter), that conjugates with bile acid cholic acid to form taurocholic acid.
• Cysteine sulfinate may undergo transamination and give rise to sulfate.
IMPORTANCE OF CYSTEINE

• The conversion of cysteine to pyruvate accounts for glucogenic nature and involved in
formation of glucose.
• Cysteine is most important dietary source of sulfur.
• Besides taurine, other physiologically important sulfur containing compounds such as
insulin, coenzyme-A, glutathione and vasopressin are derived from cysteine.
• It is also involved in detoxification mechanisms.
 METABOLIC DISORDERS

Cystinuria (Cystin-lysinuria) Cystinosis (cystine storage disease)

• Cystinuria is the most common inborn error of amino acid transport. Cystinosis is a rare but serious lysosomal disorder.

• Cystinuria is an inherited disorder in which kidney tubules fail to reabsorb the Cause: It is caused by a defective carrier that transports cystine
amino acids cystine, ornithine, arginine and lysine (the mnemonic is COAL). across the lysosomal membrane from lysosomal vesicles to the
cytosol.
• This is characterized by massive urinary excretion of cystine, ornithine,
arginine and lysine. Clinical features:
Cause: Normally, these amino acids are filtered by the glomerulus and • Cystine accumulates in the lysosomes in many tissues and forms
crystals impairing their function.
reabsorbed in the proximal renal tubule by specific carrier proteins. In
• Cystinosis is usually accompanied by a generalized
cystinuria defect in this carrier system leads to the excretion of all these four aminoaciduria.
amino acids. • Patients usually die within 10 years due to acute renal failure.
Clinical features: Since cystine is the least soluble its overexcretion often leads
to precipitation and formation of cystine calculi (stones) in the renal tubules and
leads to obstruction, infection and renal insufficiency in cystinuric patient.
Treatment Treatment involves ingestion of large amounts of water, which
increases cystine solubility through maintenance of alkaline urine.
Homocystinuria
Homocystinurias are a group of disorder of methionine metabolism. It is characterized by high blood and urinary levels of
homocysteine and methionine. Four metabolic defects cause four types of homocystinuria.
Homocystinuria type-I
It is due to defect in the enzyme cystathionine synthase, which converts homocysteine to cysthathionine. (Figure 14.25). As a
result, homocysteine accumulates in blood and appears in urine.
The accumulation of homocysteine causes skeletal abnormalities, ectopia lentis (dislocation of the lenses in the eyes),
osteoporosis, mental retardation and thrombosis. • Thrombosis may result in myocardial infarction, pulmonary embolism or
stroke.
A deficiency of cystathionine synthase is the most common cause of homocystinuria. Other types of homocystinuria are due to
defects in the remethylation of homocysteine to form methionine.
Homocystinuria type-II and III
In type-II and III, there is deficiency in synthesis of N5 -methyltetrahydrofolate and methyl B12 respectively. Both N5 -methyl
THF and methyl B12 are required for the remethylation of homocysteine to form methionine. Homocystinuria type-IV It is due
to defective intestinal absorption of vitamin B12.
Treatment:
The biochemical defect in cystathionine synthase can be corrected in some cases by providing pyridoxine (vitamin B6).
Pyridoxine is needed to activate the enzyme cystathionine synthase.
Those with complete enzyme deficiency should be treated with a diet low in methionine and supplemented with cysteine.
Vitamin B12 may be given in instances of vitamin B12 deficiency.
GLYCINE
Glycine is a nonessential or dispensable amino acid.
Synthesis of Glycine:
• It is synthesized from serine by removal of hydroxymethyl group from the side chain of serine.
• The methylene carbon group of hydroxymethyl is transferred to tetrahydrofolate and the hydroxy
group is released as water (Figure 14.12).
• This reaction is reversible, allowing glycine and serine to be interconverted.
Catabolism of Glycine: Glycine is catabolized by following three ways:
1. It can be converted into serine, a 3-carbon amino acid, by addition of hydroxy methyl group carried by the
coenzyme tetrahydrofolate (THF)
2. The major pathway of glycine degradation is oxidative cleavage of glycine into CO2 and NH4 + and a
methylene group (CH2) which is accepted by THF. This reversible reaction is catalyzed by glycine synthase.
N5 ,N10-methylene THF is used in certain biosynthetic pathways.
3. Glycine may be oxidatively deaminated by glycine oxidase to glyoxylic acid.
• Glyoxylic acid formed:

– May be decarboxylated to yield formaldehyde (formate) and CO2

– May also be converted to malate and then metabolized by the citric acid cycle.
– May be oxidized to oxalate and excreted.
• Metabolic defect of glyoxylate metabolism, associated with failure to convert glyoxylate to formate, as a result
excess of glyoxylate is oxidized to oxalate.
CATABOLISM OF GLYCINE
 IMPORTANCE OF GLYCINE

Glycine is necessary for the formation of following products:

1. Synthesis of heme: Glycine along with succinyl CoA serves as a precursor for heme synthesis.
2. Synthesis of glutathione: Glycine is required for the formation of biologically important peptide, glutathione (γ-glutamyl-cysteinyl-
glycine).
3. Formation of purine ring: Glycine is required for the formation of purine ring. It provides C4, C5 and N7 of the purine ring.
4. Formation of bile acids: The bile acids cholic acid and chenodeoxy cholic acid are conjugated with glycine to form glycocholic acid
and glycochenodeoxy cholic acid respectively. Conjugation lowers the pK of the bile salts, making them better detergents.
5. Glycine is involved in detoxification reactions, e.g. benzoic acid is detoxicated by conjugating with glycine to hippuric acid.
6. Synthesis of creatin: Glycine is necessary for the formation of creatine. Creatin is present in muscle and brain tissue as the high
energy compound creatin phosphate. Phosphocreatine functions as a store of high energy phosphate in muscle.
7. Collegen formation: In collagen glycine occurs at every third position of a chain of the triple helix.
8. Glysine is glucogenic amino acid, thus involved in the synthesis of glucose.
9. Glycine is constituent of various tissue proteins, hormones and enzymes.
10. By way of glyoxylate, it may form formate, which by THF may be incorporated into wide variety of biologically active compounds.
METABOLIC DISORDERS OF GLYCINE

Primary hyperoxaluria
• It is an inborn error, characterized by high urinary excretion of oxalate.
• The metabolic defect involves a failure to catabolize glyoxylate, which therefore gets oxidized to oxalate.
• Increased level of oxalate results in urolithiasis (stone in urinary tract), nephrocalcinosis (presence of Ca deposits in
kidneys) and recurrent infections of urinary tract.
• Death occurs in childhood or early adult life from renal failure or hypertension.

Glycinuria
• It is an inborn error characterized by increased excretion of glycine through urine, despite plasma concentration of
glycine is normal.
• Since plasma levels are normal, glycinuria occurs probably due to a defect in renal tubular reabsorption of glycine.
• Glycinuria is characterized by increased tendency for the formation of oxalate renal stones.
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