AMINO ACID METABOLISM

Close-up view of the active site of amino transferase with PLP

Chatchawin Petchlert, Ph.D.

Dept. of Biochemistry
Faculty of Science, Burapha University
Digestion

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Overview of the catabolism of amino acids

During starvation or in DM

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Amino group catabolism

Overview of
catabolism of
amino groups
in vertebrate
liver.

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Excretory forms of nitrogen

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Nitrogen assimilation (Transamination)

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 COO COO

CH2 CH2

CH3 CH2 CH3 CH2

HC NH3+ + C O C O + HC NH3+

COO COO COO COO

alanine -ketoglutarate pyruvate glutamate

Aminotransferase (Transaminase)
The 3-C a-keto acid pyruvate is produced from alanine,
cysteine, glycine, serine, & threonine.
Alanine deamination via Transaminase directly yields
pyruvate.
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 COO COO

COO CH2 COO CH2

CH2 CH2 CH2 CH2

HC NH3+ + C O C O + HC NH3+

COO COO COO COO

aspartate -ketoglutarate oxaloacetate glutamate

Aminotransferase (Transaminase)
The 4-C Krebs Cycle intermediate oxaloacetate is produced
from aspartate & asparagine.
Aspartate transamination yields oxaloacetate.
Aspartate is also converted to fumarate in Urea Cycle.
Fumarate is converted to oxaloacetate in Kreb’s cycle.

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PLP bound to active sites of
the Asp aminotransferase

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 phosphorus Side chain of Lys258
PLP

2-methylaspartate
(substrate analog)

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Glutamate dehydrogenase

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Gln transports
NH3 in the
bloodstream
(Glutaminase)

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Glucose-Alanine Cycle
Ala serves as a carrier of NH3
and of the C-skeleton of
pyruvate from muscle to liver.
The NH3 is excreted and the
pyruvate is used to produce
glucose, which is returned to
the muscle.

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UREA CYCLE

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Links between the urea cycle and TCA cycle

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 Summary of the point
of entry of the standard
amino acids into the
citric acid. Some amino
acids are listed more than once
because they yield more than
one end product. The figure
shows the major catabolic
pathways in vertebrate animals,
but there are minor variations
among vertebrate species.
Threonine, for instance, is
degraded to acetyl-CoA via
pyruvate in some organisms.

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Some enzyme cofactors important in one-carbon
transfer reactions

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Synthesis of methionine and S-adenosylmethionine in
an activated-methyl cycle

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Catabolic pathways for
alanine, glycine, serine,
cysteine, tryptophan, and
threonine

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Two metabolic fates of glycine.
(a) Conversion to serine and
(b) Breakdown to CO2 and NH4+. Tetrahydrofolate carries
one-carbon units in both of these reactions.

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Catabolic
pathways for
Trp, Lys, Phe,
Tyr, Leu, and Ile
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Tryptophan as
precursor gives
rise to nicotinate,
indoleacetate,
and serotonin.

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Catabolic pathways for
phenylalanine and
tyrosine

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Phenylalanine Hydroxylase 7,8-dihydrobiopterin
includes a non-heme iron
atom at its active site.
X-ray crystallography has
shown that the active site
iron atom has His N, Glu O Glu
His
& water O ligands.
(Fe shown in spacefill & His
ligands in ball & stick). Phenylalanine
PDB 1DMW Hydroxylase

O2, tetrahydrobiopterin, and the iron atom in the ferrous (Fe++)

oxidation state participate in the hydroxylation.
O2 is thought to react initially with the tetrahydrobiopterin to
form a peroxy intermediate.
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Genetic deficiency Transaminase
of Phenylalanine Phenylalanine Phenylpyruvate
Hydroxylase leads (Phenylketone)
Phenylalanine Deficient in
to the disease Hydroxylase Phenylketonuria
phenylketonuria.
Tyrosine Melanins
Phenylalanine &
phenylpyruvate Multiple
Reactions
(the product of
phenylalanine Fumarate + Acetoacetate

deamination via transaminase) accumulate in blood & urine.

Mental retardation results unless treatment begins immediately

after birth. Treatment consists of limiting phenylalanine intake to
levels barely adequate to support growth. Tyrosine, an essential
nutrient for individuals with phenylketonuria, must be supplied
in the diet.
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 Transaminase
Phenylalanine Phenylpyruvate
(Phenylketone)
Phenylalanine Deficient in
Hydroxylase Phenylketonuria

Tyrosine Melanins
Multiple
Reactions

Fumarate + Acetoacetate

Tyrosine is a precursor for synthesis of melanins and of

epinephrine and norepinephrine.
High [phenylalanine] inhibits Tyrosine Hydroxylase, on the
pathway for synthesis of the pigment melanin from
tyrosine. Individuals with phenylketonuria have light skin &
hair color.
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Alternative pathways
for catabolism of
phenylalanine in
phenylketonuria.
Phenylpyruvate accumulates in
the tissues, blood, and urine.
Phenylacetate and
phenyllactate can also be found
in the urine.

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Catabolic pathways for arginine, histidine,
glutamate, glutamine, and proline.

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Catabolic pathways for
methionine, isoleucine,
threonine, and valine

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Catabolic pathways for the three branched-chain
amino acid: valine, isoleucine, and leucine.

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Catabolic pathway for
asparagine and
aspartate

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 Amino Acid Carbon Skeletons

Amino acids, when deaminated, yield -keto acids

that, directly or via additional reactions, feed into
major metabolic pathways (e.g., Krebs Cycle).
Amino acids are grouped into 2 classes, based on
whether or not their carbon skeletons can be
converted to glucose:
 glucogenic
 ketogenic.

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Carbon skeletons of glucogenic amino acids are
degraded to:
 pyruvate, or
 a 4-C or 5-C intermediate of Krebs Cycle.
These are precursors for gluconeogenesis.
Glucogenic amino acids are the major carbon source for
gluconeogenesis when glucose levels are low.
They can also be catabolized for energy, or converted to
glycogen or fatty acids for energy storage.

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Carbon skeletons of ketogenic amino acids are
degraded to:
 acetyl-CoA, or
 acetoacetate.
Acetyl CoA, & its precursor acetoacetate, cannot yield net
production of oxaloacetate, the gluconeogenesis
precursor.
For every 2-C acetyl residue entering Krebs Cycle, 2 C
leave as CO2.
Carbon skeletons of ketogenic amino acids can be
catabolized for energy in Krebs Cycle, or converted to
ketone bodies or fatty acids.
They cannot be converted to glucose.
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Summary of the glucogenic and ketogenic amino acids

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The nitrogen cycle

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Nitrogen-fixing nodules.
(a) Root nodules of bird’s-
foot trefoil,
trefoil a legume.

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Nitrogen-fixing nodules.
(b) Artificially colorized electron micrograph of a thin section
through a pea root nodule.
nodule Symbiotic nitrogen-fixing bacteria,
or bacteroids (red), live inside the nodule cells, surrounded by
the peribacteroid membrane (blue). Bacteroids produce the
nitrogenase complex that converts atmospheric nitrogen (N2)
to ammonium (NH4+); without the bacteroids, the plant is unable
to utilize N2. The infected root cells provide some factors
essential for nitrogen fixation, including leghemoglobin. This
heme protein has a very high binding affinity for oxygen, which
strongly inhibits nitrogenase.
nitrogenase (The cell nucleus is shown in
yellow/green. Not visible in this micrograph are other organelles
of the infected root cell that are normally found in plant cells.)

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Allosteric regulation of
glutamine synthetase

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Overview of amino acid
biosynthesis

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Biosynthesis of
proline

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Biosynthesis of
arginine from
glutamate in bacteria

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Ornithine -aminotransferase reaction: a step in the
mammalian pathway to proline

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Biosynthesis of serine
from 3-phosphoglycerate
and of glycine from
serine in all organisms

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Biosynthesis of cysteine from serine in bacteria and plants

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Biosynthesis of cysteine from homocystein
and serine in mammals

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Biosynthesis of chorismate,
and intermediate in the
synthesis of aromatic
amino acids in bacteria and
plants

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Biosynthesis of chorismate,
and intermediate in the
synthesis of aromatic
amino acids in bacteria and
plants (cont.)

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Biosynthesis of histidine in bacteria and plants

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Allosteric regulation of
isoleucine biosynthesis

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Biosynthesis of
protoporphyrin IX,
the porphyrin of
hemoglobin and myoglobin
in mammals

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Biosynthesis of creatine and phosphocreatine

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Biosynthesis and Structure of Glutathione

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Biosynthesis of two plant
substances from amino
acids

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Biosynthesis of some
neurotransmitters from
amino acids

(Decarboxylation)

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Biosynthesis of spermine
from methionine

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