Biochemistry for Health Science Amino acid metabolism

AMINO ACID METABOLISM

Digestion

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

Chatchawin Petchlert, Ph.D.

Dept. of Biochemistry
Faculty of Science, Burapha University 2

Overview of the catabolism of amino acids Amino group catabolism

During starvation or in DM

Overview of
catabolism of
amino groups
in vertebrate
liver.

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Biochemistry for Health Science Amino acid metabolism

Nitrogen assimilation (Transamination)

Excretory forms of nitrogen

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COO− COO− COO− COO−

− −
COO CH2 COO CH2
CH2 CH2
CH2 CH2 CH2 CH2
CH3 CH2 CH3 CH2
HC NH3+ + C O C O + HC NH3+
HC NH3+ + C O C O + HC NH3+
− − −
COO COO COO COO−
COO− COO− COO − COO−
aspartate α-ketoglutarate oxaloacetate glutamate
alanine α-ketoglutarate pyruvate glutamate Aminotransferase (Transaminase)
Aminotransferase (Transaminase)
The 4-C Krebs Cycle intermediate oxaloacetate is produced
The 3-C a-keto acid pyruvate is produced from alanine, from aspartate & asparagine.
cysteine, glycine, serine, & threonine. Aspartate transamination yields oxaloacetate.
oxaloacetate.
Aspartate is also converted to fumarate in Urea Cycle.
Alanine deamination via Transaminase directly yields Fumarate is converted to oxaloacetate in Kreb’
Kreb’s cycle.
pyruvate.
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Biochemistry for Health Science Amino acid metabolism

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Biochemistry for Health Science Amino acid metabolism

phosphorus Side chain of Lys258

PLP

PLP bound to active sites of 2-methylaspartate

the Asp aminotransferase (substrate analog)

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Glutamate dehydrogenase

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Biochemistry for Health Science Amino acid metabolism

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

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UREA CYCLE

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Biochemistry for Health Science Amino acid metabolism

Links between the urea cycle and TCA cycle

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Biochemistry for Health Science Amino acid metabolism

Some enzyme cofactors important in one-

one-carbon
transfer reactions

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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Synthesis of methionine and S-adenosylmethionine in

an activated-
activated-methyl cycle

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Biochemistry for Health Science Amino acid metabolism

Catabolic pathways for

alanine, glycine, serine,
cysteine, tryptophan,
tryptophan, and
threonine

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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Tryptophan as
precursor gives
rise to nicotinate,
nicotinate,
indoleacetate,
indoleacetate,
and serotonin.

Catabolic
pathways for
Trp, Lys, Phe,
Tyr, Leu, and Ile
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Biochemistry for Health Science Amino acid metabolism

Phenylalanine Hydroxylase 7,8-dihydrobiopterin

Catabolic pathways for includes a non-
non-heme iron
phenylalanine and atom at its active site.
tyrosine 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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Transaminase
Genetic deficiency Transaminase Phenylalanine Phenylpyruvate
of Phenylalanine Phenylalanine Phenylpyruvate (Phenylketone)
Hydroxylase leads (Phenylketone) Phenylalanine Deficient in
to the disease Phenylalanine Deficient in Hydroxylase Phenylketonuria
Hydroxylase Phenylketonuria
phenylketonuria.
phenylketonuria.
Tyrosine Melanins
Tyrosine Melanins
Phenylalanine & Multiple
phenylpyruvate Multiple
Reactions
Reactions
(the product of
phenylalanine Fumarate + Acetoacetate 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,
Tyrosine, an essential
nutrient for individuals with phenylketonuria, must be supplied in
the diet.
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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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Catabolic pathways for arginine, histidine,

histidine,
Alternative pathways glutamate, glutamine, and proline.
for catabolism of
phenylalanine in
phenylketonuria.
phenylketonuria.
Phenylpyruvate accumulates in
the tissues, blood, and urine.
Phenylacetate and
phenyllactate can also be found
in the urine.

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Biochemistry for Health Science Amino acid metabolism

Catabolic pathways for the three branched-

branched-chain
amino acid: valine, isoleucine,
isoleucine, and leucine.
Catabolic pathways for
methionine, isoleucine,
isoleucine,
threonine, and valine

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Catabolic pathway for Amino Acid Carbon Skeletons

asparagine and
aspartate
Amino acids, when deaminated, yield α-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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Biochemistry for Health Science Amino acid metabolism

Carbon skeletons of ketogenic amino acids are

Carbon skeletons of glucogenic amino acids are degraded to:
degraded to:

acetyl-CoA, or

pyruvate, or
acetoacetate.

a 4-C or 5-C intermediate of Krebs Cycle. Acetyl CoA, & its precursor acetoacetate, cannot yield net
These are precursors for gluconeogenesis. production of oxaloacetate, the gluconeogenesis
precursor.
Glucogenic amino acids are the major carbon source for
gluconeogenesis when glucose levels are low. For every 2-C acetyl residue entering Krebs Cycle, 2 C
leave as CO2.
They can also be catabolized for energy, or converted to Carbon skeletons of ketogenic amino acids can be
glycogen or fatty acids for energy storage. 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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Biochemistry for Health Science Amino acid metabolism

The nitrogen cycle

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

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Biochemistry for Health Science Amino acid metabolism

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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Biochemistry for Health Science Amino acid metabolism

Biosynthesis of
Overview of amino acid proline
biosynthesis

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Biosynthesis of
arginine from
glutamate in bacteria

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Biochemistry for Health Science Amino acid metabolism

Ornithine δ-aminotransferase reaction: a step in the

mammalian pathway to proline

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

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Biochemistry for Health Science Amino acid metabolism

Biosynthesis of cysteine from serine in bacteria and plants Biosynthesis of cysteine from homocystein
and serine in mammals

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

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Biosynthesis of chorismate,
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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Biochemistry for Health Science Amino acid metabolism

Allosteric regulation of
isoleucine biosynthesis

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

Biosynthesis of two plant

substances from amino
acids

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Biochemistry for Health Science Amino acid metabolism

Biosynthesis of some
neurotransmitters from
amino acids

(Decarboxylation)

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Biochemistry for Health Science Amino acid metabolism

Biosynthesis of spermine
from methionine

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