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8/3/2019 9 Metabolism of AAs
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Metabolism of Amino Acids.
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The fate of absorbed Amino Acids.
In the liver AAs are used for
1) the synthesis of intrinsic proteins2) blood plasma proteins
3) the liver provides for a balancedpool of free amino acids viasynthesis of nonessential AAs
and redistribution of nitrogen bytransamination reactions.
4) for the production of specific
nitrogen-containing compounds
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Sourcesand
fates ofamino
acids.
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Nitrogen containing compounds (30 g/day)
porphyrins (heme, Hb, cytochromes) creatine purines, pyrimidines (DNA, RNA)
neurotransmitters biogenic amines nicotinamide NAD+ melanins (pigments) ammonia Urea Uric acid
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The absorbed amino acids areprimary used as building materials
for the synthesis of specific tissueproteins, enzymes, hormones andother biologically active compounds.
A certain number of amino acidsundergo breakdown to yield the endproducts of protein metabolism (CO2,
H2O and NH3) and to generateenergy (10% of the dailyrequirementof the human organism in energy).
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Amino acid, like proteins are
not deposited in the tissues forreserve purposes (in distinctionto fats and glycogen).
Amino acids concentrations inthe blood of an adult human ismaintained at a constant level(under the conditions of normalsupply with dietary proteins).
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Biological value of dietary proteins. To have the high biological value protein
should have1) all essential amino acids in its
composition (PVT TIM HALL)
Lack of any of the essential amino acidsin the diet leads to a negative nitrogenbalance, physical waste, growthretardation, nervous system disturbancesand other pathologic symptoms.
1) and similar composition of aminoacids of body proteins.
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The more close is the proteindiet to the amino acid
composition of body proteins,the higher is its biological
value. For instance, the proteins of meat,milk and egg are biologically of
greater value for man (since theiramino acid compositions are close tothe amino acid composition of human
tissues and organs).
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Biological value of proteinsof animal origin is higherthan proteins of vegetableorigin.
Because of this reason, for thesynthesis of the same amount ofintrinsic body proteins, the human
organism requires much moredietary vegetable proteins thananimal proteins.
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Protein reserves.The term reserve proteins refers to
tissue proteins that can be easilymobilized to supply amino acid needs ofthe body. Proteins of
liver, muscles and blood plasma(albumin) can be used as
a specific reserve material.The liver and muscles are the first to losemass, while the mass of brain or heartremains essentially unaffected.
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Putrefaction of amino acids. The intestinal microflora has a set of
enzymes distinct from human enzymes(catalyze putrefactive breakdown ofamino acids in the large intestine).
The formation of both
toxic products of amino acidbreakdown (phenol, indole, cresol,skatole, hydrogen sulphide and methyl
mercaptan) and non-toxic compounds (alcohols, amines,
fatty acids, keto acids and hydroxyacids) are formed in the large intestine.
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Putrefaction of sulphur-containing amino acids.
In the course of gradual breakdown of
sulphur-containing amino acids(cystine, cysteine and methionine)
hydrogen sulphide (H2S) and
methyl mercaptan (CH3SH)
are formed in large intestine).
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Diamino acids (ornithine and lysine)undergo decarboxylation to yield amines
(putescine and cadaverine).
Ornithin
-CO2
putrescine
Lysine -CO2 cadaverine
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The aromatic amino acids(phenylalanine, tyrosine) and tryptophan,
when subjected to an analogous bacterialdecarboxylationyield the relevant amines:
phenylethylamine,
p-hydroxyphenylethylamine (tyramine),
indolylethylamine (triptamine).
Then gradual breakdown of the sidechains takes place and toxic metabolites
are formed cresol
phenol,
skatole and indole, respectively.
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Tyrosine
tyramine (p-hydroxyphenylethylamine)
cresol
phenol
-CO2
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Tryptophan
tryptamine
skatole
indole
-CO2
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To be detoxified, these productsare delivered, though the portalvein, to the liver where theybecome bound with activated
sulphuric acid or glucuronic acid
to produce non-toxic conjugatedacids (e.g. phenol-sulfuric orskatoxylsulpfuric acid) excreted
in the urine.
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Sulfuric and glucuronic acids arepresent in their active forms:
3-phosphoadenosine-5-phosphosulphate(PAPS);
uridinediphosphoglucuronicacid (UDP-glucuronate).
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Indole becomes bound in the form of asulphuric acid ester.
Its salt, potassium indoxyl sulphate(indican) is excreted in the urine.
Determination of indican concentation
in the human urine allows
to estimate the rate of proteinputrefaction in the intestine as well
as
to diagnose the functional state of
the liver.
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Catabolism of amino acidcarbon skeletons The catabolism of the 20 amino acids involves
the removal of -amino groups and then thebreakdown of carbon skeletons 7 products areformed:
oxaloacetate,
-ketoglutarate, pyruvate,
fumarate,
acetyl-CoA, acetoacetyl-CoA and
succinyl-CoA.
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Complete ketogenic AAS:
leucine and
lysine
are converted to acetoacetate and are notconverted to metabolites of CAC.
Glucoketogenic AAs are
isoleucine,
phenylalanine,
tyrosine,
tryptophan.
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Isoleucine AcetylCoA acetoacetate
SuccinylCoA
Phenylalanine
Tyrosine
acetoacetatefumarate
Tryptophan acetoacetatepyruvate
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Other AAs areconverted to
metabolites of CAC orpyruvate and thats
why they areglucogenic.
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AAs can also be classified as or essential,semiessential or nonessential according
to whether or not they can be synthesizedin humans.
Essential AAs (PVT TIM HALL):
Phenylalanine, valine, tryptophan,threonine, isoleucine, methionine,leucine, lysine.
Semiessential AAs (HA):
Histidine, arginine essential forinfants, not essential for adults.