protein metabolism dea farha fira darson fine
TRANSCRIPT
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Arrange by :
Darson; Dea Apriyani; Elfira Bauzir; Farhati Mardhiyah
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*Overview of Amino Acid Catabolism:
Interorgan Relationships
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*Overview of Amino Acid Catabolism:
Interorgan Relationships
Intestine
Dietary amino acids absorbed
Utilizes glutamine and asparagine asenergy sources
Releases CO2, ammonium, alanine,citrulline as endproducts
Utilizes glutamine during fasting forenergy
Dietary amino acids and catabolitesreleased to portal blood
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*Overview of Amino Acid Catabolism:
Interorgan Relationships
Liver
Synthesis of liver and plasma proteins
Catabolism of amino acids Gluconeogenesis
Ketogenesis
Branched chain amino acids not
catabolized Urea synthesis
Amino acids released into generalcirculation
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*Overview of Amino Acid Catabolism:
Interorgan Relationships
Skeletal Muscle
Muscle protein synthesis
Catabolism of BCAA
Amino groups transported away as alanineand glutamine (50% of AA released)
Alanine to liver for gluconeogenesis
Glutamine to kidneys
Kidney Glutamine metabolized to a-KG + NH4
a-KG for gluconeogenesis
NH4 excreted or used for urea cycle
(arginine synthesis)
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*Vitamin-Coenzymes
in Amino Acid Metabolism
Vitamin B-6 (pyridoxal phosphate)
Folic acid (tetrahydrofolate) Vitamin B-12
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*Vitamin-Coenzymes in Amino Acid
Metabolism
Vitamin B-12
Catabolism of BCAA
Methyl-malonyl CoA mutase
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*Vitamin-Coenzymes
in Amino Acid Metabolism
Vitamin B-6 : pyridoxal
phosphate
Enzymes that bind aminoacids use PLP as
coenzyme for binding
Transaminases
Amino acid
decarboxylases
Amino acid deaminases
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*Vitamin-Coenzymes
in Amino Acid Metabolism
Folacin: Tetrahydrofolate(THF)
Carrier of single carbons
Donor & receptor
Glycine and serine
Tryptophan degradation
Histidine degradation Purine and pyrimidine
synthesis
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Transamination is a enzimatic reaction that
moving -amino groups into -carbon in -
ketoglutarate.
Released -keto acid and L-glutamate.
Occur: cytosol
Function: to release and collect only one type of
amino acid, that is L-glutamate.
L-glutamate is source of oxidative deamination.
*Transamination
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The first step in the catabolism of most amino acids is
removal of a-amino groups by enzymes transaminases or
aminotransferases.
All aminotransferases have the same prostethic group
and the same reaction mechanism.
The prostethic group is pyridoxal phosphate (PLP), the
coenzyme form of pyridoxine (vitamin B6).
*Transamination
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*Transamination
Amino groups can be
removed by
transamination
In liver cytosol, amino
groups are dumped to
-KG, forming
glutamate.
Transaminases (aka
aminotransferases)
require pyridoxal
phosphate cofactor.
Removal of amino
group via
transamination
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*Biosynthesis of Amino Acid: Transamination
Reactions
Example of aTransaminase reaction:
Aspartate donates its
amino group, becomingthe a-keto acidoxaloacetate.
a-Ketoglutarate accepts
the amino group,becoming the amino acidglutamate.
aspartate -ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase)
COO
CH2
CH2
C
COO
O
COO
CH2
HC
COO
NH3+
COO
CH2
CH2
HC
COO
NH3+
COO
CH2
C
COO
O+ +
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*Transamination
Pyridoxal phosphate and transamination
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Mechanism of
transamination
reaction
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*In the cytosoL amino
groups from most aminoacids are transferred to
-ketoglutarate to form
glutamate, which enters
mitochondria and gives up
its amino group to form
NH4+.
*Excess ammonia
generated in most other
tissues is converted tothe amide nitrogen of
glutamine, which passes
to the liver, then into
liver mitochondria.17
Transamination
(cytosol)
Deamination
(Mitochondria)
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Four types of deamination:- oxidative(the most important for higher animals),- reduction,- hydrolytic, and- intramolecular
elimination of amino groupfrom amino acid with
ammonia formation
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Reduction deamination:
R-CH(NH2)-COOH + 2H+ R-CH2-COOH + NH3amino acid fatty acid
Hydrolytic deamination:
R-CH(NH2)-COOH + H2O R-CH(OH)-COOH + NH3amino acid hydroxyacid
Intramolecular deamination:
R-CH(NH2)-COOH R-CH-CH-COOH + NH3amino acid unsaturated fatty acid
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L-Glutamate dehydrogenaseplays a central role in amino aciddeamination
In most organisms glutamate is the only amino acid that hasactive dehydrogenase
Present in both the cytosol and mitochondria of the liver
O X I D A T I V E D E A M I N A T I O N
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Glutamate Releases Its Amino Groupas Ammonia in the Liver
The -ketoglutarate formed fromglutamate deamination can beused in the citric acid cycle andfor glucoseSynthesis
The fate of the NH4 produced by anyof these deamination Processes. Inthe liver the ammonia from allsources is disposed of by ureasynthesis.
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Glutaminemetabolism
disposed of byurea synthesis.
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Six Amino Acids Are Degraded to Pyruvate
alanine, tryptophan, cysteine, serine, glycine, andthreonine
Seven Amino Acids Are Degraded to Acetyl-CoA
tryptophan, lysine, phenylalanine, tyrosine, leucine,isoleucine, and threonine
Five Amino Acids Are Converted to Ketoglutarate
proline, glutamate, glutamine, arginine, andhistidine
Four Amino Acids Are Converted to Succinyl-CoA
methionine, isoleucine, threonine,and valine
Two amino acids are converte to oxaloacetate
Asparagine and aspartate
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*Alanine yields pyruvate directly on transamination withketoglutarate
alanine -ketoglutarate pyruvate glutamate Aminotransferase (Transaminase)
COO
CH2
CH2
C
COO
O
CH3
HC
COO
NH3+
COO
CH2
CH2
HC
COO
NH3+
CH3
C
COO
O+ +
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Threonine
pyruvate
-ketobutyrate Succinyl CoA
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Inter conversion of serine and glycine
Serine can be converted to glycine and
N5, N10-methylenetetrahydorfolate or topyruvateby serine dehydratase.
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The major route of cysteine degradationmost likely starts by the oxidation of
cysteine to 3-sulfinoalanine. The
conversion of L-cysteine to 3-
sulfinoalanine (L-cysteine sulfinic acid)
forms a branch point. In one route, 3-
sulfinoalanine is transaminated by 3-sulfinoalanine aminotransferase to 3-
sulfinyl-pyruvate, which spontaneously
degrades to pyruvate and sulfite. Sulfite is
oxidized by sulfite oxidase to sulfate,
which is excreted in the urine, and
pyruvate is converted by pyruvatedecarboxylation to acetyl CoA to acetyl-
CoA, which enters the TCA cycle I
(prokaryotic).
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Tryptophan breakdown is the most complex of all thepathways of aminoacid catabolism in animal tissues;portions of tryptophan (four of its carbons) yieldacetyl-CoA via acetoacetyl- CoA.
Some of the intermediates in tryptophan catabolismare precursors for the synthesis of other biomolecules,including nicotinate, a precursor of NADand NADP inanimals; serotonin, a neurotransmitter in vertebrates;and indoleacetate, a growth factor in plants.
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Transamination of tyrosine to p-hydroxyphenylpyruvate is catalyzed bytyrosine -ketoglutarate transaminase
(tyrosine aminotransferase).
P-hydroxyphenylpyruvate formshomogentisate catalysed by p-
hydroxyphenylpyruvate dioxygenasewhere ascorbic acid is the reductant.
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Lysine is an entirely ketogenic amino acid.
There is an initial transamination of the -amino groupwhich requires -ketoglutarate as the acceptor and
cosubstrate.
The resulting compound is -ketoadipate which formsacetoacetyl CoA.
* Figure 26-23 The
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1. Saccharopine dehydrogenase
(NADP+, Lys forming)
2. Saccharopine dehydrogenase
(NAD+, Glu forming)
3. Aminoadipate semialdehyde
dehydrogenase
4. Aminoadipate aminotransferase
(PLP)
5. -keto acid dehydrogenase
6. Glutaryl-CoA dehydrogenase
7. Decarboxylase
8. Enoyl-CoA hydratase
9. -hydroxyacyl-CoA
dehydrogenase
10. HMG-CoA synthase
11. HMG-CoA lyase
gpathway of lysine
degradation inmammalian liver.
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Leucine and isoleucine also give acetyl CoA. Moredetails will be explained in branched chain amino acid
catabolism.