Learning Objectives 1 Know the groups of aa biosynthetic families 2 The enzymes and coenzymes involved in the synthetic pathways 3 The enzyme deficiencies of each pathway 4 The consequences of the inborn errors of metabolism ID: 908680
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Slide1
Amino Acid Biosynthesis & Degradation
Learning Objectives :
1. Know the groups of
a.a
. biosynthetic families
2. The enzymes and coenzymes involved in the synthetic pathways
3. The enzyme deficiencies of each pathway.
4. The consequences of the inborn errors of metabolism
Slide2Amino
Acid Biosynthetic Families,Grouped by Metabolic Precursor
α
-
Ketoglutarate
Pyruvate
Glutamate Alanine
Glutamine
Valine
*
Proline
Leucine
*
Arginine Isoleucine*
3-Phosphoglycerate
Phosphoenolpyruvate
and
Serine
erythrose
4-phosphate
Glycine Tryptophan*
Cysteine Phenylalanine*
Oxaloacetate
Tyrosine
Aspartate
Ribose
5-phosphate
Aspargine
Histidine
*
Methionine*
Threonine*
Lysine*
Slide3Biosynthetic Families of Amino Acids in Bacteria and Plants
Slide4Pyruvate as an Entry Point into Metabolism
Pyruvate is the entry point of the three-carbon amino acids alanine, serine, and cysteine into the
metabolic mainstreamThe transamination of alanine directly yields pyruvate.Glutamate is then oxidatively deaminated, yielding NH4+ and regenerating α-ketoglutarate. The sum of these reactions is
Slide5Another simple reaction in the degradation of amino acids is the
deamination of serine to pyruvate
by serine dehydratase
Slide6Methionine Metabolism
Slide7Activated Methyl Cycle. The methyl group of methionine is activated by the formation of
S
adenosylmethionine
Slide8Oxygenases
Are Required for the Degradation of Aromatic Amino Acids
The degradation of phenylalanine begins with its hydroxylation to tyrosine, a reaction catalyzed by phenylalanine hydroxylase. This enzyme is called a monooxygenase (or mixed-function oxygenase) because one atom of O2 appears in the product and the other in H2O.
Slide9Phenylalanine & Tyrosine Degradation
Slide10Phenylalanine
Catabolism Is Genetically Defectivein
Some
People
Genetic
defects
of
amino
acid
metabolism
can
cause
defective
neural
development
and mental
retardation
.
In
most
such
diseases
specific
intermediates
accumulate.
For example
,
a
genetic
defect
in
phenylalanine
hydroxylase
,
The first
enzyme
in
the catabolic
pathway
for
phenylalanine
,
is
responsible
for
the
disease
phenylketonuria
(PKU),
the
most
common
cause
of
elevated
levels
of
phenylalanine
(
hyperphenylalaninemia
).
Slide11The incidence of phenylketonuria is about 1 in 20,000 newborns. The disease is inherited in an
autosomal recessive
manner. Heterozygotes, who make up about 1.5% of a typical population, appear normal. Carriers of the phenylketonuriagene have a reduced level of phenylalanine hydroxylase, as indicated by an increased level of phenylalanine in the blood
Slide12Because
the
major outflow pathway is blocked in phenylketonuria, the blood level of phenylalanine is typically at least 20-fold as high as in normal people. Minor fates of phenylalanine in normal people, such as the formation of phenylpyruvate, become major fates in phenylketonurics.
Slide13Slide14Alcaptonuria
is an inherited metabolic disorder caused by the absence of homogentisate oxidase.
Slide15Slide16The Branched-Chain Amino Acids Yield Acetyl CoA, Acetoacetate,
or
Propionyl CoAThe degradative pathways of valine and isoleucine resemble that of leucine. After transamination and oxidative decarboxylation to yield a CoA derivative, the subsequent reactions are like those of fatty acid oxidation.Isoleucine yields acetyl CoA and propionyl CoA, whereas valine yields CO2 and propionyl CoA.
Slide17Slide18Tryptophan Degradation.
The pathway for the conversion of tryptophan into alanine and acetoacetate
Slide19Histidine
Degradation Conversion of histidine into glutamateGlutamate Formation. Conversion of proline and arginine into glutamate
Slide20Succinyl CoA Formation.
Conversion of methionine, isoleucine, and
valine into succinyl CoA
Slide21Some Human Genetic Disorders Affecting Amino Acid Catabolism
Medical condition
Defective processDefective enzymeSymptoms and effectsAlbinismMelanin synthesisfrom tyrosineTyrosine 3-monooxygenase(Tyrosinase)Lack of pigmentation:white hair, pink skinAlkaptonuriaTyrosine degradationHomogentisate
1,2-dioxygenase
Dark
colour
of urine; late developing
Arthritis
Argininemia
Urea synthesis
Arginase
Mental retardation
Slide22Medical condition
Defective process
Defective enzymeSymptoms and effectsCarbamoyl phosphate synthetase Ideficiency Urea synthesisCarbamoyl phosphatase ILethargy; convulsions;early deathHomocystinuriaMethionine
degradation
Cystathionine
–
β
synthase
Faulty bone development;
mental
retardation
Maple syrup urine disease (branched-
chain
ketoaciduria
)
Isoleucine
,
leucine
,
&
Valine
degradation
Branched-chain –
α
keto
acid
dehydrogenase
complex
Vomiting; convulsions mental retardation, early death
Slide23Medical condition
Defective process
Defective enzymeSymptoms and effectsMethylmalonic acidemiaConversion of propionyl-CoA to succinyl-CoAMethylmalonyl-CoAmutaseVomiting; convulsions;mental retardation;Early deathPhenylketonuria
Conversion of phenylalanine to tyrosine
Phenylalanine
hydroxylase
Neonatal vomiting
Mental retardation
Slide24Inherited
defects of
a.a.met. almost result inmental retardation or other developmental abnormalities as a result of harmful accumulation of metabolites .
Slide25END
of PROTEIN METABOLISM