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Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi ١ Amino Acids Metabolism Amino Acids Metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١
Amino Acids MetabolismAmino Acids Metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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• Cysteine•• CysteineCysteine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
٣
CysteineCysteine
• It is α-amino, β-thiol propionic
• It is nonnon--essentialessential amino acid
• It is glucogenic glucogenic amino acid
StructureStructure
Nutrional ValueNutrional Value
Metabolic FateMetabolic Fate
CH2
SH
CH
NH2
COOH
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
٤
CysteineCysteineBiosynthesis 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
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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CysteineCysteine
1. Incorporated in protein structure•• HormonesHormones•• EnzymesEnzymes
2. Biosynthesis of cystine 3. Synthesis of thioethanolamine 4. Biosynthesis of glutathione 5. It gives pyruvic acid6. Synthesis of glucose 7. Biosynthesis of taurine8. Bile acids and salts9. Detoxication
Metabolic FateMetabolic Fate
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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CysteineCysteine22-- Synthesis of cystineSynthesis of cystine
CH2 CH
NH2
COOHSH
CH2
S
CH
NH2
COOH
CH2 CH
NH2
COOHS
2 Cysteine Cystine
++Cysteine reductaseCysteine reductase
NAD+ NADH.H+CH2
SH
CH
NH2
COOH
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
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CysteineCysteine33-- Formation of thioethanolamineFormation of thioethanolamine
DecarboxylationeDecarboxylatione
CO2
Cysteine Thioethanolamine
CH2
SH
CH
NH2
COOH CH2
SH
CH2
NH2
CoA.SH
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
٨
CysteineCysteine44-- Biosynthesis of glutathioneBiosynthesis of glutathione
CH2
COOH
NH2
CH CNHCH2
SH
CCH2
CH2HC
COOHNH2
O
CH2
COOH
NHO
Glutath
ione s
ynthe
tase
(γ Glutamyl cysteinyl glycine)Glutathione
ADP+Pi Glycine
ATP
ADP+Pi
γ Glutamyl cysteinesynthetase
ATP
γ Glutamyl cysteine
H2OCH COOHNHCH2
SH
CCH2
CH2HC
COOHNH2
OCOOHCH2
CH2HC
COOHNH2
Glutamic acid
Cysteine
CH COOHNH2
CH2
SH+
H2O
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
٩
CysteineCysteine55-- Formation of pyruvic acidFormation of pyruvic acid
CH3 C
NH
COOH CH3 C
O
COOH
Desulfhydrase Desulfhydrase
H2S H2O NH3
PLPCysteine
α imino propionic Pyruvic acid
CH3 C
O
COOH
Transamination Sulpher transferase
2Hα KG Glu
PLP
Cysteine Thiolpyruvic Pyruvic acid
CH2
SH
CH
NH2
COOH
CH2
SH
CH
NH2
COOH CH2
SH
C
O
COOHH2S
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٠
CysteineCysteine66-- Glucose biosynthesisGlucose biosynthesis
Pyruvic acidCysteine
Glucose
DesulfhydraseDesulfhydrase
Gluc
oneo
gene
sis
Gluc
oneo
gene
sis
CysteineTransaminationTransamination
Thiolpyruvic
Cysteine OxidationOxidationCysteine sulfinic
Sulfinyl pyruvic
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١١
CysteineCysteine77-- Biosynthesis of taurineBiosynthesis of taurine
CH2
SH
CH
NH2
COOH
CH2
SO3H
CH
NH2
COOH
CH2
SO2H
CH
NH2
COOH
CH2
SO3H
CH2
NH2
CH2 CH2 SO3HNH2
DioxygenaseDioxygenase
O2Cysteine Cysteine sulfinic
Cysteic acidTaurine CO2
O
DecarboxylaseDecarboxylase
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٢
CysteineCysteine8 8 –– Conjugation with bile acidsConjugation with bile acids
C
HO HOH
OH
OS.CoA
CoA.SH
Cholyl CoA
Taurocoholic Acid
+
K taurocoholateNa taurocoholate
KNa
CH2CH2 SO3HNH2
C
HO H OH
OH
OCH2CH2 SO3HNH
C
HO H OH
OH
OCH2CH2 SO3NaNH C
HO H OH
OH
OCH2CH2SO3KNH
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٣
CysteineCysteine99-- Detoxication of bromophenolDetoxication of bromophenol
Br
CH2HS CH
NH2
COOH
CH2S CH
NH2
COOH
Br
CH2S CH
HN
COOH
C CH3
O
Br
Acetyl CoA+
CoA.SHBromophenol
Bromophenyl mercapturic
Bromophenyl cysteine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٤
CysteineCysteine99-- Detoxication of naphthaleneDetoxication of naphthalene
CH2HS CH
NH2
COOH CH2S CH
NH2
COOH
CH2S CH
HN
COOH
C CH3
O
Acetyl CoA+
CoA.SH
Naphthalene
Naphthyl mercapturic
Naphthyl cysteine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٥
CysteineCysteine
1.1. Nonoxidative deaminationNonoxidative deamination to pyruvic acid
2.2. TransaminationTransamination to Thiolpyruvic acid
3.3. Direct oxidationDirect oxidation to Cysteine sulfinic acid
Catabolic FateCatabolic Fate
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٦
CysteineCysteine11--Nonoxidative deaminationNonoxidative deamination to pyruvic acid
CH3 C
NH
COOH CH3 C
O
COOH
Desulfhydrase Desulfhydrase
H2S H2O NH3
PLPCysteine
α imino propionic Pyruvic acid
CH2
SH
CH
NH2
COOH
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٧
CH2
SH
CH
NH2
COOH
CH2
SH
C
O
COOH
CH3 C
O
COOH
CH2
SH
CH
OH
COOH
H2SNa
Na2SO3Na2SO4
2HNAD+
NADH.H+
Lactate dehydrogenaseLactate dehydrogenase Sulpher transferaseSulpher transferase
Sulphite oxidaseSulphite oxidase
Sodium sulphiteSodium sulphate
3 mercaptolactic
3 mercaptopyruvic
Pyruvic acid
Cysteine
TransaminaseTransaminase
22--TransaminationTransamination to thiolpyruvic acid
Thiolpyruvic
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٨
CysteineCysteine33-- Direct oxidationDirect oxidation to cysteine sulfinic acid
DioxgenaseDioxgenaseCysteine sulfinic
O2Cysteine
Pyruvic acid
TransaminaseTransaminaseα KG
Glu
Sulfinyl pyruvic
CH2
SH
CH
NH2
COOH
CH2
SO2H
CH
NH2
COOH
CH2
SO2H
C
O
COOHCH3 C
O
COOH
SO3--
DesulfinaseDesulfinase
Cysteic acidTaurine
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
١٩
CysteineCysteine
•• 11-- Cystinuria Cystinuria
• Marked increase in urinary cystine,
lysine, arginine and ornithine.
• Defective renal tubular reabsorption of
these amino acids.
Inborn errors of cysteine metabolismInborn errors of cysteine metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
٢٠
CysteineCysteine
•• 22-- Cystinosis Cystinosis
• Cystine accumulates in lysosomes• No transport to cytoplasm• Deposition of cystine crystals in tissues• Impaired renal functions • Generalized amino aciduria• Renal failure
Inborn errors of cysteine metabolismInborn errors of cysteine metabolism
Prof Dr Mohammad Ibrahim Prof of Medical Biochemistry http://osp.mans.edu.eg/medbiochem_mi
٢١
SelenocysteineSelenocysteine
• Selenocysteine occurs at the active site of many enzymes:–– Glutathione peroxidase Glutathione peroxidase –– DeiodinaseDeiodinase–– Thioredoxin reductase Thioredoxin reductase
• Selenocysteine-tRNA is first charged with serine• Subsequent replacement of the serine oxygen by
selenium
CH2
SeH
CH
NH2
COOHCH2
OH
CH
NH2
COOH
