ccccccccccccccccccccccccccccccccccccccccccccIntroduction

‡All tissues have some capability for synthesis of the non-

essential amino acids, amino acid remodeling, and conversion
of non-amino acid carbon skeletons into amino acids and other
©

c site of nitrogen metabolism in the body. In times
of dietary surplus, the potentially toxic nitrogen of amino acids
is eliminated via transaminations, deamination, and urea
formation; the carbon skeletons are generally conserved as
carbohydrate, via gluconeogenesis, or as fatty acid via fatty
acid synthesis pathways. In this respect amino acids fall into
three categories:
1.cglucogenicM
x.cketogenicM or
3.cglucogenic and ketogenic×
‡Glucogenic amino acids are those that give rise to a net
production of pyruvate or TCA cycle intermediates, such as Į-
ketoglutarate or oxaloacetate, all of which are precursors to
glucose via gluconeogenesis. All amino acids except lysine and
leucine are at least partly glucogenic. Lysine and leucine are
the only amino acids that are solely ketogenic, giving rise only
to acetylCoA or acetoacetylCoA, neither of which can bring
about net glucose production.
‡A small group of amino acids comprised of isoleucine,
phenylalanine, threonine, tryptophan, and tyrosine give rise to
both glucose and fatty acid precursors and are thus
characterized as being glucogenic and ketogenic. Finally, it
should be recognized that amino acids have a third possible
 fate. During times of starvation the reduced carbon skeleton is
used for energy production, with the result that it is oxidized to
COx and HxO.

cccccccccccccccccccccccccccccccccc
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ccccccccccccccccc
cccccccccccccccŒ
ntial and Non

ntial Amino Acid

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c c
1.cAlanine
x.cAsparagine
3.cAspartate
4.cCysteine
5.cGlutamate
6.cGlutamine
7.cGlycine
8.cProline
9.cSerine
10.c Tyrosine
Πc

c c
1.cArginine
x.cHistidine
3.cIsoleucine
4.cLeucine
5.cLysine
6.cMethionine
7.cPhenylalanine
8.cThreonine
9.cTyrptophan
10.Valine
‡The amino acids arginineM methionine and phenylalanine are
considered essential for reasons not directly related to lack of
 synthesis. Arginine is synthesized by mammalian cells but at a
rate that is insufficient to meet the growth needs of the body
and the majority that is synthesized is cleaved to form urea.
Methionine is required in large amounts to produce cysteine if
the latter amino acid is not adequately supplied in the diet.
Similarly, phenyalanine is needed in large amounts to form
tyrosine if the latter is not adequately supplied in the diet.

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cccccccccccccccccccccccccccccAmino Acid Cataboli mc
їGlutamin
Glutamat
and A aragin
A artat

Cataboli m:
‡Glutaminase is an important kidney tubule enzyme involved in
converting glutamine (from liver and from other tissue) to
glutamate and NH4+, with the NH4+ being excreted in the urine.
Glutaminase activity is present in many other tissues as well,
although its activity is not nearly as prominent as in the kidney.
The glutamate produced from glutamine is converted to Į-
ketoglutarate, making glutamine a glucogenic amino acid.

‡Asparaginase is also widely distributed within the body, where

it converts asparagine into ammonia and aspartate. Aspartate
transaminates to oxaloacetate, which follows the
gluconeogenic pathway to glucose.
‡Glutamate and aspartate are important in collecting and
eliminating amino nitrogen via glutamine synthetase and the
urea cycle, respectively. The catabolic path of the carbon
skeletons involves simple 1-step aminotransferase reactions
that directly produce net quantities of a TCA cycle
intermediate. The glutamate dehydrogenase reaction operating
in the direction of Į-ketoglutarate production provides a second
avenue leading from glutamate to gluconeogenesis×cc
c
 Alanin
Cataboli m
‡Alanine is also important in intertissue nitrogen transport as
part of the glucose-alanine cycle. Alanine's catabolic pathway
involves a simple aminotransferase reaction that directly
produces pyruvate. Generally pyruvate produced by this
pathway will result in the formation of oxaloacetate, although
when the energy charge of a cell is low the pyruvate will be
oxidized to COx and HxO via the PDH complex and the TCA
cycle. This makes alanine a glucogenic amino acid.
ccccccccccccccArginin
 Ornithin
and Prolin
Cataboli m
‡The catabolism of arginine begins within the context of the urea
cycle. It is hydrolyzed to urea and ornithine by arginase.
‡Ornithine, in excess of urea cycle needs, is transaminated to
form glutamate semialdehyde. Glutamate semialdehyde can
serve as the precursor for proline biosynthesis as described
above or it can be converted to glutamate.
‡Proline catabolism is a reversal of its synthesis process.
‡The glutamate semialdehyde generated from ornithine and
proline catabolism is oxidized to glutamate by an ATP-
independent glutamate semialdehyde dehydrogenase. The
glutamate can then be converted to Į-ketoglutarate in a
transamination reaction. Thus arginine, ornithine and proline,
are glucogenic×cc
ccccccccccccccccccccccccccccccccccccD
rin
Cataboli m
‡The serine is converted to glycine and then glycine
oxidised to COx and NH3, with the production of two
equivalents of ©5,©10-methyleneTHF. Serine can be
catabolized back to the glycolytic intermediate, 3-
phosphoglycerate, by a pathway that is essentially a
reversal of serine biosynthesis. However, the enzymes
are different. Although it has been demonstrated in
mammals such as rodents and dogs that serine can be
converted to pyruvate through a deamination reaction
catalyzed by serine/threonine dehydratase, this enzyme
is lacking in humans.
 ½hr
onin
Cataboli mc
‡There are at least 3 pathways for threonine catabolism although
only two are significant in humans. One involves a pathway
initiated by threonine dehydrogenase yielding Į-amino-ȕ-
ketobutyrate. The Į-amino-ȕ-ketobutyrate is either converted to
acetyl-CoA and glycine, via the action of Į-amino-ȕ-
ketobutyrate lyase, or it can spontaneously degrade to
aminoacetone which is converted to pyruvate.
‡The second pathway utilizes serine hydroxymethyltransferase.
This enzyme belongs to a family of one-carbon transferases
and is alternatively named glycine hydroxymethyltransferase
and threonine aldolase. The products of this reaction are acetyl-
CoA and glycine. The glycine can be converted to serine via
the same enzyme and the serine is then catabolized yielding
pyruvate and NH4+. Thus, via this catabolic pathway threonine
yields ketogenic and glucogenic byproducts.
‡The additional pathway involves serine/threonine dehydratase
yielding Į-ketobutyrate which is further catabolized to
propionyl-CoA and finally the TCA cycle intermediate,
succinyl-CoA. However, the serine/threonine dehydratase
enzyme is expressed in many mammalian species, it is not
expressed in humans.
cccccccccccccccccccccccccccccccccGlycin
Cataboli m
‡Glycine is classified as a glucogenic amino acid, since it can be
converted to serine by serine hydroxymethyltransferase, and
serine can be converted back to the glycolytic intermediate, 3-
phosphoglycerate or to pyruvate by serine/threonine
dehydratase. Nevertheless, the main glycine catabolic pathway
leads to the production of COx, ammonia, and one equivalent
of ©5,©10-methyleneTHF by the mitochondrial glycine
decarboxylase, also called the glycine cleavage complex, GCC.
ccccccccccccccccccccccccccccccccccccCy t
in
Cataboli m
‡There are several pathways for cysteine catabolism. The
simplest, but least important pathway is catalyzed by a liver
desulfurase and produces hydrogen sulfide, (HxS) and
pyruvate. The major catabolic pathway in animals is via
cysteine dioxygenase that oxidizes the cysteine sulfhydryl to
sulfinate, producing the intermediate cysteinesulfinate.
Cysteinesulfinate can serve as a biosynthetic intermediate
undergoing decarboxylation and oxidation to produce taurine.
Catabolism of cysteinesulfinate proceeds through
transamination to ȕ-sulfinylpyruvate which then undergoes
desulfuration yielding bisulfite, (HSO3±) and the glucogenic
product, pyruvate. The enzyme sulfite oxidase uses Ox and HxO
to convert HSO3± to sulfate, (SO4±) and HxOx. The resultant
sulfate is used as a precursor for the formation of 3'-
phosphoadenosine-5'-phosphosulfate, (PAPS). PAPS is used
for the transfer of sulfate to biological molecules such as the
sugars of the glycosphingolipids.
 c

‡Other than protein, the most important product of cysteine

metabolism is the bile salt precursor taurine, which is used to
form the bile acid conjugates taurocholate and
taurochenodeoxycholate.
‡The enzyme cystathionase can also transfer the sulfur from one
cysteine to another generating thiocysteine and pyruvate.
Transamination of cysteine yields ȕ-mercaptopyruvate which
then reacts with sulfite, (SO3x±), to produce thiosulfate, (SxO3x±)
and pyruvate. Both thiocysteine and thiosulfate can be used by
the enzyme rhodanese to incorporate sulfur into cyanide, (CN±
), thereby detoxifying the cyanide to thiocyanate.
 M
thionin
Cataboli m
‡The principal fates of the essential amino acid methionine are
incorporation into polypeptide chains, and use in the
production of Į-ketobutyrate and cysteine via SAM. The
transulfuration reactions that produce cysteine from
homocysteine and serine also produce Į-ketobutyrate, the latter
being converted first to propionyl-CoA and then via a 3-step
process to succinyl-CoA.
‡Regulation of the methionine metabolic pathway is based on
the availability of methionine and cysteine. If both amino acids
are present in adequate quantities, SAM accumulates and is a
positive effector on cystathionine synthase, encouraging the
production of cysteine and Į-ketobutyrate (both of which are
glucogenic). However, if methionine is scarce, SAM will form
only in small quantities, thus limiting cystathionine synthase
activity. Under these conditions accumulated homocysteine is
remethylated to methionine, using ©5-methylTHF and other
compounds as methyl donors.
 ccccccc‰alin
 L
ucin
and I ol
ucin
Cataboli m
‡This group of essential amino acids are identified as the
branched-chain amino acids, BCAAs. Because this
arrangement of carbon atoms cannot be made by humans, these
amino acids are an essential element in the diet. The catabolism
of all three compounds initiates in muscle and yields NADH
and FADHx which can be utilized for ATP generation. The
catabolism of all three of these amino acids uses the same
enzymes in the first two steps. The first step in each case is a
transamination using a single BCAA aminotransferase, with Į-
ketoglutarate as amine acceptor. As a result, three different Į-
keto acids are produced and are oxidized using a common
branched-chain Į-keto acid dehydrogenase (BCKD), yielding
the three different CoA derivatives. Subsequently the metabolic
pathways diverge, producing many intermediates.
‡The principal product from valine is propionylCoA, the
glucogenic precursor of succinyl-CoA. Isoleucine catabolism
terminates with production of acetylCoA and propionylCoA;
thus isoleucine is both glucogenic and ketogenic. Leucine gives
rise to acetylCoA and acetoacetylCoA, and is thus classified as
strictly ketogenic.
‡There are a number of genetic diseases associated with faulty
catabolism of the BCAAs. The most common defect is in the
branched-chain Į-keto acid dehydrogenase, BCKD. Since there
is only one dehydrogenase enzyme for all three amino acids, all
three Į-keto acids accumulate and are excreted in the urine.
The disease is known as Maple syrup urine disease because of
the characteristic odor of the urine in afflicted individuals.
Mental retardation in these cases is extensive. Unfortunately,
since these are essential amino acids, they cannot be heavily
restricted in the diet; ultimately, the life of afflicted individuals
is short and development is abnormal.The main neurological
problems are due to poor formation of myelin in the CNS.
 cccccccPh
nylalanin
and ½yro in
Cataboli m
‡Phenylalanine normally has only two fates: incorporation into
polypeptide chains, and production of tyrosine via the
tetrahydrobiopterin-requiring phenylalanine hydroxylase. Thus,
phenylalanine catabolism always follows the pathway of
tyrosine catabolism. The main pathway for tyrosine
degradation involves conversion to fumarate and acetoacetate,
allowing phenylalanine and tyrosine to be classified as both
glucogenic and ketogenic.
‡Tyrosine is equally important for protein biosynthesis as well as
an intermediate in the biosynthesis of several physiologically
important metabolites e.g. dopamine, norepinephrine and
epinephrine (Specialized Products of Amino Acids).
‡As in phenylketonuria (deficiency of phenylalanine
hydroxylase, PAH), deficiency of tyrosine aminotransferase
(TAT) leads to hypertyrosinemia and the urinary excretion of
tyrosine and the catabolic intermediates between phenylalanine
and tyrosine. The adverse neurological symptoms are similar
for PAH and TAT deficiencies. In addition, hypertyrosinemia
leads to painful corneal eruptions and photophobia.
‡The first inborn error in metabolism ever recognized,
alkaptonuria, was demonstrated to be the result of a defect in
phenylalanine and tyrosine catabolism. Alkaptonuria is caused
by defective homogentisic acid oxidase. Homogentisic acid
accumulation is relatively innocuous, causing urine to darken
on exposure to air, but no life-threatening effects accompany
the disease. The only untoward consequence of alkaptonuria is
ochronosis (bluish-black discoloration of the tissues) and
arthritis.
 ccccccccccccccccccccccLy in
Cataboli m
‡Lysine catabolism is unusual in the way that the İ-amino group
is transferred to Į-ketoglutarate and into the general nitrogen
pool. The reaction is a transamination in which the İ-amino
group is transferred to the Į-keto carbon of Į-ketoglutarate
forming the metabolite, saccharopine. Unlike the majority of
transamination reactions, this one does not employ pyridoxal
phosphate as a cofactor. Saccharopine is immediately
hydrolyzed by the enzyme Į-aminoadipic semialdehyde
synthase in such a way that the amino nitrogen remains with
the Į-carbon of Į-ketoglutarate, producing glutamate and Į-
aminoadipic semialdehyde. Because this transamination
reaction is not reversible, lysine is an essential amino acid. The
ultimate end-product of lysine catabolism is acetoacetyl-CoA.
‡Genetic deficiencies in the enzyme Į-aminoadipic
semialdehyde synthase have been observed in individuals who
excrete large quantities of urinary lysine and some
saccharopine. The lysinemia and associated lysinuria are
benign. Other serious disorders associated with lysine
metabolism are due to failure of the transport system for lysine
and the other dibasic amino acids across the intestinal wall.
Lysine is essential for protein synthesis; a deficiencies of its
transport into the body can cause seriously diminished levels of
protein synthesis. Probably more significant however, is the
fact that arginine is transported on the same dibasic amino acid
carrier, and resulting arginine deficiencies limit the quantity of
ornithine available for the urea cycle. The result is severe
hyperammonemia after a meal rich in protein. The addition of
citrulline to the diet prevents the hyperammonemia.
‡Lysine is also important as a precursor for the synthesis of
carnitine, required for the transport of fatty acids into the
mitochondria for oxidation. Free lysine does not serve as the
precursor for this reaction, rather the modified lysine found in
certain proteins. Some proteins modify lysine to
trimethyllysine using SAM as the methyl donor to transfer
methyl groups to the İ-amino of the lysine side chain.
Hydrolysis of proteins containing trimethyllysine provides the
substrate for the subsequent conversion to carnitine.

c
 cccccccccccccccccccu
  c

c
‡Histidine catabolism begins with release of the Į-amino group
catalyzed by histidase, introducing a double bond into the
molecule. As a result, the deaminated product, urocanate, is not
the usual Į-keto acid associated with loss of Į-amino nitrogens.
The end product of histidine catabolism is glutamate, making
histidine one of the glucogenic amino acids.
‡Another key feature of histidine catabolism is that it serves as a
source of ring nitrogen to combine with tetrahydrofolate
(THF), producing the 1-carbon THF intermediate known as ©5-
formiminoTHF. The latter reaction is one of two routes to ©5-
formiminoTHF. Urocanate is converted to 4-imidazolone-5-
propionate via the action of urocanate hydratase. The latter
product is then converted to ©-formiminoglutamte via the
action of imidazolone propionase. Glutamate
formiminotransferase then transfers the fomimino group to
THF yielding glutamate and ©5-formiminoTHF.
‡The principal genetic deficiency associated with histidine
metabolism is absence or deficiency of the first enzyme of the
pathway, histidase. The resultant histidinemia is relatively
benign. The disease, which is of relatively high incidence (1 in
10,000), is most easily detected by the absence of urocanate
from skin and sweat, where it is normally found in relative
abundance.
‡Decarboxylation of histidine in the intestine by bacteria gives
rise to histamine. Similarly, histamine arises in many tissues by
the decarboxylation of histidine, which in excess causes
 constriction or dilation of various blood vessels. The general
symptoms are those of asthma and various allergic reactions×c

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 ½rytohan Cataboli m
‡A number of important side reactions occur during the
catabolism of tryptophan on the pathway to acetoacetate. The
first enzyme of the catabolic pathway is an iron porphyrin
oxygenase that opens the indole ring. The latter enzyme is
highly inducible, its concentration rising almost 10-fold on a
diet high in tryptophan.
‡Kynurenine is the first key branch point intermediate in the
catabolic pathway leading to 3 fates:
1.Kynurenine can undergo deamination in a standard
transamination reaction yielding kynurenic acid.
x.Kynurenic acid and metabolites have been shown to act as
antiexcitotoxics and anticonvulsives.
3.High levels of kynurenic acid have been found in the urine of
individuals suffering from schizophrenia.
‡Kynurenic acid has been shown to act as a non-competetive
antagonist at the glycine binding site of the NMDA receptor
(NMDA = ©-methyl-D-aspartate) which is an ionotropic
(ligand-gated ion channel) receptor for glutamate. The NMDA
receptor is a key component of the glutaminergic
neurotransmission system believed to be involved in the
pathophysiology of schizophrenia, thus explaining the potential
role of kynurenic acid in schizophrenia.
‡Kynurenine can also undergo a series of catabolic reactions
producing 3-hydroxyanthranilic acid plus alanine. Another
equivalent of alanine is produced from kynurenine in a single
step reaction leading to anthranilic acid. It is the production of
these alanine residues that allows tryptophan to be classified
among the glucogenic amino acids. Oxidation of 3-
hydroxyanthranilate converts it into x-amino-3-
carboxymuconic 6-semialdehyde, which has two fates. The
main flow of carbon elements from this intermediate leads to
acetoacetate which is why tryptophan is also a ketogenic amino
acid. An important side reaction in liver involves a non-
enzymatic cyclization to quinolate then via a transamination
and several rearrangements yields limited amounts of nicotinic
acid, which leads to production of a small amount of NAD+
and NADP+.
‡Aside from its role as an amino acid in protein biosynthesis,
tryptophan also serves as a precursor for the synthesis of
serotonin and melatonin.

cc
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cccccccccccccccccccccccc
ë
 

  
Π 
1. carbamoylphosphate synthetase
x. ornithine transcarbamoylase
3. argininosuccinate synthetase
4. argininosuccinase
5. arginase.
  

    
  


D : D  :

Geetanjali Ma¶am Arvind Kumar Maurya
AIMT M.Sc. Micro. 3rd sem
A0901x09019
1.Introduction
x.Amino Acids
3.Amino Acid Degradation
-Glutamine/Glutamate and Asparagine/Aspartate Catabolism
-Alanine Catabolism
-Arginine, Ornithine and Proline Catabolism
-Serine Catabolism
-Threonine Catabolism
-Glycine Catabolism
-Cysteine Catabolism
-Methionine Catabolism
-Valine, Leucine and Isoleucine Catabolism
-Phenylalanine and Tyrosine Catabolism
-Lysine Catabolism
-Histidine Catabolism
-Tryptophan Catabolism

4.Pathways of amino acid degradation

5.Urea cycle and the citric acid cycle
ccccccccccccccccccccccccccccccccccc c
1.Lehninger (Biochemistry)
x.Satyanarayan (Biochemistry)
3. www.google.com
  

    
  


  

D D  

Dr. Harsha Kharakwal Swaran Shekhar Johri
M.Sc.3rd sem.
A0901x0900x
1.Dubey and Maheshwari (Microbiology)
x.Lehninger (Biochemistry)
3.www.wikipedia.com
4.Research paper by Terje Traavik University of Tromsö and
Norwegian Institute of Gene Ecology, Tromsö, Norway
1.Types of Vaccines
- Live whole virus vaccines

- Killed whole virus vaccines

- Subunit vaccines;- purified or recombinant viral antigen

- Recombinant virus vaccines

- Anti- idiotype antibodies

- DNA vaccines
x.Recombinant technology
3.Recombination techniques
4.Approaches to vaccine production
5.Research paper