1 Overview The catabolism of the amino acids involves Removal of αamino groups Breakdown of the resulting carbon skeletons The resulting compounds will be used to form seven intermediate products ID: 775056
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Synthesis and degradation of Amino acids
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Slide2Overview The catabolism of the amino acids involves:Removal of α-amino groups. Breakdown of the resulting carbon skeletons.The resulting compounds will be used to form seven intermediate products: oxaloacetate, α-ketoglutarate, pyruvate, fumarate, succinyl coenzyme A (CoA), acetyl CoA, and acetoacetate. These products directly enter the pathways of intermediary metabolism, resulting either in the synthesis of glucose or lipid or in the production of energy through their oxidation to CO2 and water by the Krebs cycle.
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Slide4Essential amino acids in humans
Arginine* Histidine* Isoleucine Leucine Valine
Lysine Methionine Threonine Phenylalanine Tryptophan
*Required to some degree in young growing period and/or sometimes during illness.
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Slide5Non-essential amino acids in humans
Alanine Asparagine Aspartate Glutamate Glutamine
Glycine Proline Serine Cysteine (from Met*) Tyrosine (from Phe*)
* Essential amino acids
Can be formed from a-keto acids by transamination and subsequent reactions.
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Slide6Metabolic relationship of amino acids
BODY PROTEINS
Proteosynthesis
Degradation
AMINO ACIDS
DIETARY
PROTEINS
GLYCOLYSIS
KREBS CYCLE
Digestion
Transamination
NONPROTEIN
DERIVATIVES
Porphyrins
Purines
Pyrimidines
Neurotransmitters
Hormones
Komplex lipidsAminosugars
UREA
NH
3
Conversion
(Carbon skeleton)
250 – 300
g/day
ACETYL CoA
GLUCOSE
CO
2
KETONBODIES
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Slide7Biosynthesis of amino acids :transamination reactionsAll amino acids except threonine, lysine, and proline can be transaminated
amino acid1 +a-keto acid2 amino acid2 +a-keto acid1
Glutamate
+
a
-
Ketoglutarate
+
Pyridoxal phosphate (PLP)-
d
ependent
a
minotransferase
Keto-acid
Amino acid
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Slide8Clinicaly
important transaminases
ALT
Alanine-a-ketoglutarate transferase ALT(also called glutamate-pyruvate transaminase – GPT)Aspartate-a-ketoglutarate transferase AST(also called glutamate-oxalacetate transferase – GOT)Important in the diagnosis of heart and liver damage caused by heart attack, drug toxicity, or infection.
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Slide9Glucose-alanine cycle
Ala
is the carrier of ammonia and of the carbon skeleton of pyruvate from muscle to liver.The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle.
Alanine plays a special role in transporting amino groups to liver.
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Slide10Glucogenic Amino Acids
formed: a-ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl-CoA
Aspartate Asparagine ArginineProline
Methionine Valine Glutamine Glutamate Threonine
Alanine Serine Cysteine Glycine Histidine
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Slide11Ketogenic Amino Acids
formed acetyl CoA or acetoacetate
LysineLeucine
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Slide12Both glucogenic and ketogenic amino acids
formed: a-ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl-CoA in addition to acetyl CoA or acetoacetate
IsoleucineTryptophanPhenylalanineTyrosine
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Slide1313
Slide14Alanine
Serine
Cysteine
Threonine
The C3 family: alanine, serine, cysteine and threonine are converted to pyruvate
Pyruvate
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Slide15The C4 family: aspartate and asparagine are converted into oxalacetate
Aspartic acid
Asparagine
Oxalacetate
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Slide16The C5 family: several amino acids are converted into a-ketoglutarate through glutamate
Glutamine
Proline
Histidine
Arginine
a-
ketoglutarate
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Slide17Interconversion of amino acids and intermediates of carbohydrate metabolism and Krebs cycle
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Slide18Synthesis of Ala, Val, and Lue
—Ala, Val, and Lue are derived from pyruvate (EMP)
carbon skeleton
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Slide19Synthesis of Ser, Gly and Cys
—Ser, Gly, and Cys are derived from 3-phosphoglycerate
(EMP)
carbon skeleton
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Slide20Synthesis of Glu, Gln, Pro and Arg
—α-Ketoglutarate (TCA) gives rise to Glu, Gln, Pro, and Arg synthesis
carbon skeleton
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Slide21—Oxaloacetate(TCA) gives rise to Asp, Asn, Met, Lys, Thr synthesis
carbon skeleton
Synthesis of
Asp, Asn, Met, Lys,Thr and Arg
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Slide22Synthesis of His
carbon skeleton
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Slide23Diseases related to the amino acid metabolism
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Slide24There is a not a proven cause and effect relationship of elevated homocysteine with cardiovascular disease.Elevated plasma homocysteine levels are an independent cardiovascular risk factor that correlates with the severity of coronary artery disease.Dietary supplementation with folate, vitamin B12 and vitamin B6 the three vitamins involved in the metabolism of homocysteine to a reduction in circulating levels of homocysteine.
Role of homocysteine in vascular disease
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Slide25Deficiency of phenylalanine hydroxylase (common) or deficiencies in the enzymes that synthesize or reduce the coenzyme BH4.Elevated levels of phenylalanine, phenyl- lactate, phenylpyruvate in plasma and urine characteristic mousey odor of urine.
CNS symptoms: Mental retardation, failure to walk or talk, seizures, hyperactivity, tremor
Hypopigmentation:
deficiency of
pigmentation (fair hair, light skin color, and blue eyes) < hydroxylation of tyrosine by tyrosinase, which is the first step in the formation of the pigment melanin
Phenyl ketouria
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Slide26Neonatal diagnosis of PKU : laboratory
testing for elevated blood levels of
phenylalanine is mandatoryHowever, fetus at birth normal level of phenyl-alanine (mother) tests performed at birth may show false negative results exposure of new born to protein diet 24 h after birth better results.Treatment of PKU: feeding synthetic amino acid preparations low in phenylalanine, supplemented with some natural foodsMaternal PKU : When mother suffering from PKU + high level on phenylanaline microcephaly, mental retardation, and congenital heart abnormalities in the fetusDietary control of blood phenylalanine prior to conception, and must be maintained throughout the pregnancy
Phenyl ketouria
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Slide27A rare metabolic disease involving a deficiency in
accumulation
acid oxidase acid
(degenerative pathway of
homogentisic homogentisic tyrosine)Characteristic
symptoms:
homogentisic aciduria
which is oxidized to a dark pigment on standinglarge joint arthritis and black pigmentation of cartilage and collagenous tissuePatients are without symptoms till 40Diets low in protein may help
Alkaptonuria
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Slide28AlbinismA group of conditions with a defect in tyrosine metabolism a deficiency in the production of melanin partial or full absence of pigment from the skin, hair, and eyes.Oculo-cutaneous albinism: due to a deficiency of tyrosinase activity, causing a total absence of pigment from the hair, eyes, and skin The most severe form of the condition. Affected people may appear to have white hair, skin, and photophobia (sunlight is painful to their eyes), they sunburn easily, and do not tan.
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