Last time we discussed urea cycle in which the amino groups that
are released in the form of ammonia are converted to urea that is
less toxic, so can be excreted by urine.
The common structure between AA that is going to be metabolised
in common pathways is the amino group, the rest of the molecule
(the carbon skeleton of amino acid) go to several pathways
depending on the R group.
We divided the amino acids depending on the type of final product
they produce. If they produce kerbs cycle intermediate
(oxaloacetate, α-ketoglutarate, succinylcoA, pyruvate, etc…) these
can be used as precursors of gluconeogenesis, that is why these
amino acids considered glucogenic and amino acids produce
acetylcoA, acetoacetylcoA, these can act as precursors of
ketogenesis that’s why they considered as ketogenic. Small number can be both meaning that they go
multible pathways producing sevsral products.
1.Amino acids that form oxaloacetate
We already know that aspartate can be transaminated to
produce oxaloacetate by the action of enzyme AST.
Asparagine is very close in structure to aspartate, having
an extra amino group so it's an amide functional group in
the R chain, but aspartate has carboxyl group. So if I
remove the amino group by asparaginase enzyme
through hydrolysis reaction (we add H2O molecule to
release ammonia from asparagen producing aspartate),
then it can be transaminated to oxaloacetate.
So I consider asparagine and aspartate as amino acids
that can produce oxaloacetate.
2. Amino acids that form α-ketoglutarate via glutamate
(Glutamine, Proline, Arginine, Histidine) these can be converted to glutamate then will be deaminated
to produce α-ketoglutarate.
Glutamine structure is close to glutamate (same as asparagine and aspartate), hydrolysis of glutamine
to glutamate then deamination to α-ketoglutarate.
, Histidine has imidazole ring in the R chain, so it has to open the ring during this degredative pathway.
Same thing in proline, which has a ring between R chain and amino group.
3. Amino acids that form fumarate
Tyrosine has a benzene ring and OH group in its
R chain, so it goes multiple pathways, and
because it considered ketogenic and glucogeinc,
producing acetoacetate (form of ketone bodies)
or producing fumarate in the other pathway.
Phenylalanine can be hydroxylated to tyrosine
(+OH) by the action of phenylalanine hydroxylase
enzyme, so the degradation process of phenylalanine is the synthetic process of
Tyrosine. So phenylalanine considered as amino acid that produces fumarate, in
conclusion Phenylalanine and Tyrosine are both glucogenic and ketogenic.
Phenylalanine hydroxylase enzyme uses co-enzyme called BH4 (tetrahydrobiopterin)
having 4 hydrogens that become during the reaction BH2(dihydrobiopterin) having two
hydrogens.
The metabolism of tyrosine as well as phenylalanine is very important and connect to
several diseases, the phenylalanine hydroxylase is mutated as an enzyme in a disease
called phenylketonuria PKU, one of the most common genetic diseases that affect
amino acids metabolism.
Tyrosine metabolism is also connected to other diseases like albinism and alkaptonuria
(rare disease but it's found in Jordan, it was misdiagnosed for a long time and recently in
few years was properly diagnosed and took a special care) we will talk about it later…
4. Amino acids that form pyruvate
1. Alanine: We know that alanine is transaminated to
pyruvate by the action of the enzyme alanine
aminotransferase (ALT), and with the production of
glutamate by the amination of α-ketoglutarate.
2. Serine (alanine +OH): and you can think that when I
remove amino group and hydroxyl group I will have
production of pyruvate, and this process done by the
action of enzyme serine dehydratase.
are released in the form of ammonia are converted to urea that is
less toxic, so can be excreted by urine.
The common structure between AA that is going to be metabolised
in common pathways is the amino group, the rest of the molecule
(the carbon skeleton of amino acid) go to several pathways
depending on the R group.
We divided the amino acids depending on the type of final product
they produce. If they produce kerbs cycle intermediate
(oxaloacetate, α-ketoglutarate, succinylcoA, pyruvate, etc…) these
can be used as precursors of gluconeogenesis, that is why these
amino acids considered glucogenic and amino acids produce
acetylcoA, acetoacetylcoA, these can act as precursors of
ketogenesis that’s why they considered as ketogenic. Small number can be both meaning that they go
multible pathways producing sevsral products.
1.Amino acids that form oxaloacetate
We already know that aspartate can be transaminated to
produce oxaloacetate by the action of enzyme AST.
Asparagine is very close in structure to aspartate, having
an extra amino group so it's an amide functional group in
the R chain, but aspartate has carboxyl group. So if I
remove the amino group by asparaginase enzyme
through hydrolysis reaction (we add H2O molecule to
release ammonia from asparagen producing aspartate),
then it can be transaminated to oxaloacetate.
So I consider asparagine and aspartate as amino acids
that can produce oxaloacetate.
2. Amino acids that form α-ketoglutarate via glutamate
(Glutamine, Proline, Arginine, Histidine) these can be converted to glutamate then will be deaminated
to produce α-ketoglutarate.
Glutamine structure is close to glutamate (same as asparagine and aspartate), hydrolysis of glutamine
to glutamate then deamination to α-ketoglutarate.
, Histidine has imidazole ring in the R chain, so it has to open the ring during this degredative pathway.
Same thing in proline, which has a ring between R chain and amino group.
3. Amino acids that form fumarate
Tyrosine has a benzene ring and OH group in its
R chain, so it goes multiple pathways, and
because it considered ketogenic and glucogeinc,
producing acetoacetate (form of ketone bodies)
or producing fumarate in the other pathway.
Phenylalanine can be hydroxylated to tyrosine
(+OH) by the action of phenylalanine hydroxylase
enzyme, so the degradation process of phenylalanine is the synthetic process of
Tyrosine. So phenylalanine considered as amino acid that produces fumarate, in
conclusion Phenylalanine and Tyrosine are both glucogenic and ketogenic.
Phenylalanine hydroxylase enzyme uses co-enzyme called BH4 (tetrahydrobiopterin)
having 4 hydrogens that become during the reaction BH2(dihydrobiopterin) having two
hydrogens.
The metabolism of tyrosine as well as phenylalanine is very important and connect to
several diseases, the phenylalanine hydroxylase is mutated as an enzyme in a disease
called phenylketonuria PKU, one of the most common genetic diseases that affect
amino acids metabolism.
Tyrosine metabolism is also connected to other diseases like albinism and alkaptonuria
(rare disease but it's found in Jordan, it was misdiagnosed for a long time and recently in
few years was properly diagnosed and took a special care) we will talk about it later…
4. Amino acids that form pyruvate
1. Alanine: We know that alanine is transaminated to
pyruvate by the action of the enzyme alanine
aminotransferase (ALT), and with the production of
glutamate by the amination of α-ketoglutarate.
2. Serine (alanine +OH): and you can think that when I
remove amino group and hydroxyl group I will have
production of pyruvate, and this process done by the
action of enzyme serine dehydratase.
