amino acids metabolism - mansosp.mans.edu.eg/.../10_methionine_metabolism.pdf · amino acids...
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Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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Amino Acids MetabolismAmino Acids Metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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• Methionine•• MethionineMethionine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine
• It is α-amino, γ-methylthiol butyric
• It is essentialessential amino acid
• It is glucogenic glucogenic amino acid
StructureStructure
Nutrional ValueNutrional Value
Metabolic FateMetabolic Fate
CH2 CH
NH2
COOHCH2
SCH3
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine
1. Incorporated in protein structure
2. Synthesis of S-adenosyl methionine
3. Biosynthesis of homocysteine
4. Biosynthesis of cysteine
5. Biosynthesis of homoserine
6. Synthesis of glucose
Metabolic FateMetabolic Fate
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine22-- Synthesis of SSynthesis of S--adenosyl methionineadenosyl methionine
CH2 CH
NH2
COOHCH2
SCH3
OHOH
O
CH2Adenine
P - P - P
OHOH
O
CH2Adenine
CH2 CH
NH2
COOHCH2
SCH3
ATPH2O Pi+PPi
S-adenosyl methionine
Methionine adenosylMethionine adenosyl
transferasetransferase
+
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine
OHOH
O
CH2Adenine
CH2 CH
NH2
COOHCH2
SCH3
OHOH
O
CH2Adenine
CH2 CH
NH2
COOHCH2
S
OHOH
O
CH2Adenine OH
CH2 CH
NH2
COOHCH2
SH
33-- Synthesis of homocysteineSynthesis of homocysteine
CH3S-adenosyl methionine S-adenosyl homocysteine
HomocysteineAdenosine
+
H2O
Methionine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine44-- Biosynthesis of cysteineBiosynthesis of cysteine
CH2 CH
NH2
COOHOH
CH2 CH
NH2
COOHCH2
SH
CH2 CH
NH2
COOH
CH2 CH
NH2
COOHCH2
S
CH2
SH
CH
NH2
COOHCH2 CH
NH2
COOHCH2
OH
Serine
CysteineHomoserine
Homocysteine
Cystathionine
Cystathionine Synthetase
+
+
H2OPLP
Methionine
H2O
CystathionasePLP
55-- Biosynthesis of homoserineBiosynthesis of homoserine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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CH3CHC OS.CoA
HOOC
MethionineMethionine66-- Glucose biosynthesisGlucose biosynthesis
CH3 CH2 C COOHO
CH3CH2C OS.CoA
CH2CH2C OS.CoA
COOH
NH3Homoserine α ketobutyric Propionyl CoA
Methyl malonyl CoASuccinyl CoA
CO2PLP
DehydrataseDehydratase DehydrogenaseDehydrogenase
CarboxylaseCarboxylase CO2
MutaseMutaseBiotinMn+
CH2 CH
NH2
COOHCH2
OH
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine
HomocystinuriaHomocystinuria
•• CauseCause
• Impaired activity of the enzyme cystathionine synthase
• Excreion of large amount of homocysteine in urine
Inborn errors of methionine metabolismInborn errors of methionine metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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MethionineMethionine
SerineSerine HomocysteineHomocysteine CystathionineCystathionineCystathionine SynthetaseCystathionine Synthetase
+
MethionineMethionine
Inborn errors of methionine metabolismInborn errors of methionine metabolismHomocystinuriaHomocystinuria
cysteinecysteine+HomoserineHomoserine
∅∅
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١١
MethionineMethionineHomocystinuriaHomocystinuria
•• CauseCause
• Impaired activity of the enzyme cystathionine synthase
• Excreion of large amount of homocysteine in urine
•• SymptomsSymptoms
• Thrombosis
• Osteoporosis
• Dislocated lenses
• Mental retardation
•• TreatmentTreatment
• A diet poor in methionine and rich in cystiene.
Inborn errors of methionine metabolismInborn errors of methionine metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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• Transfer of methyl group • from methyl donordonor• to methyl acceptoracceptor
TransmethylationTransmethylationTransmethylationTransmethylation
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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1- S-Adenosyl methionine2- Choline3- Betaine4- 5 Methyl tetrahydrofolic acid
Methyl donorsMethyl donorsTransmethylationTransmethylation
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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• Guanidoacetic acid → Creatine
• Carnosine → Anserine
• Ethanolamine → Choline
• Uracil → Thymine
• Noradrenaline → Adrenaline
• N-acetyl serotonine → Melatonine
• Nicotinic acid → N Methyl nicotinic acid
• Nicotinamide → N Methyl nicotinamide
• Pyridine → N Methyl pyridine
Methyl acceptorsMethyl acceptorsTransmethylationTransmethylation