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1、University of ManitobaAdam Burgener University of ManitobaAdam Burgener Protein Amino acids keto acids Ammonia Urea excretion Pyruvate TCA intermediates etc. Energy CHC NH3 + R O O- CC O R O O- University of ManitobaAdam Burgener C O CHNH3 + CH3 O- C C O CH2 O CH2 C O- O- O Glutamate Alanine Pyruvat
2、e -KG C C O CH2 O CH2 CH O- O- NH3 +C O CO CH3 O- Alanine transaminase Transamination and deaminations involved in removal of amino group from an amino acid PLP University of ManitobaAdam Burgener Attaches to a lysine residue on the transaminase enzyme University of ManitobaAdam Burgener Enzyme NH +
3、 CH PLPLys CHC NH3 + R O O- Amino acid Enzyme CHC NH+ R O O- CH PLP NH3 + Lys OH2 CC O R O O- Keto acid Enzyme NH3 + Lys NH3 + CH2 PLP CC O R O O- Keto acid Enzyme CC NH+ R O O- CH2 PLP NH3 + Lys OH2 Enzyme CHC NH+ R O O- CH PLP NH3 + Lys CHC NH3 + R O O- New Amino acid START University of ManitobaA
4、dam Burgener Amino acid Keto acid -KG Glutamate Build-up Glutamate C C O CH2 O CH2 CH O- O- NH3 + Glutamine synthetase NH3 ATP ADP + Pi C C O CH2 O CH2 CH O- NH2 NH3 + Glutamine Glutamate C C O CH2 O CH2 CH O- O- NH3 + Glutaminase NH4 + C C O CH2 O CH2 CH O- NH2 NH3 + Glutamine OH2 Glutamate dehydro
5、genase NAD(P)+ NAD(P)H + H+ C C O CH2 O CH2 C O- O- O -KG NH4 + Urea cycleUrea cycle (blood) Liver University of ManitobaAdam Burgener University of ManitobaAdam Burgener Amino acids keto acids -KG Glu Gln NH4 + transaminase Gln synthetase Blood Gln LIVER Glu -KG NH4 + NH4 + Glutaminase Glu Dehydrog
6、enase TCA University of ManitobaAdam Burgener CH CH2 NH3 + C O O- OH Serine C CH3 O C O O- Pyruvate OH2 OH2 Serine dehydratase NH4 + PLP CH CH C O O- CO O- Fumarate CH CH2 C O O- CO O- NH3 + NH4 + Aspartate deaminase Aspartate University of ManitobaAdam Burgener NH3 C NH3 + NH3 + O Urea University o
7、f ManitobaAdam Burgener Amino acids (excess) keto acids -KG Glu NH4 + Carbamoyl Phosphate CO2 2 ATP 2 ADP + 2 Pi Ornithine Citrulline Aspartate Arginosuccinate Arginine Fumarate OAA Malate Citrulline Ornithine UREA Amino acids (excess) keto acids Glu -KG Mitochondria Cytosol 2 ATP 2 ADP + 2 Pi Unive
8、rsity of ManitobaAdam Burgener NH4 + HCO3-(1) + 2 ATP C O NH2(P) + 2 ADP + 2 Pi + 2 H+ Carbamoyl-P synthetase (2) O- O- NH3 + O O CH C C CH2 CH C CH2 CH2 CH2 NH2 NH3 + O O- Ornithine + C O NH2(P) Carbamoyl Phosphate Carbamoyl Phosphate Ornithine transcarbamoylase CO NH2 CH C CH2 CH2 CH2 NH NH3 + O O
9、- Citrulline Pi (3) CO NH2 CH C CH2 CH2 CH2 NH NH3 + O O- Citrulline + Aspartate Arginosuccinate synthetase ATP AMP + PPi 2 Pi O- O-NH OO CHC C CH2C NH2 + CH C CH2 CH2 CH2 NH NH3 + O O- Arginosuccinate (4) O- O-NH OO CHC C CH2C NH2 + CH C CH2 CH2 CH2 NH NH3 + O O- Arginosuccinate Arginosuccinate lya
10、se NH2C NH2 + CH C CH2 CH2 CH2 NH NH3 + O O- O-O- O O CHCCCH Fumarate Arginine (5) NH2C NH2 + CH C CH2 CH2 CH2 NH NH3 + O O- Arginine + OH2Arginase CH C CH2 CH2 CH2 NH2 NH3 + O O- Ornithine + NH2 C NH2 O Urea from carbamoyl-P from aspartate University of ManitobaAdam Burgener University of ManitobaA
11、dam Burgener Citrate -KG Succ CoA Fumarate OAA glu gln his pro arg Ile thr met val phe tyr asp asn leu lys phe tyr trp ile leu trp cys trp gly ser ala thr Acetoacetyl CoA AcCoA Pyruvate A B B C University of ManitobaAdam Burgener CH C O CH NH3 + OH CH3 O- C O NH3 + CH2 O- Alanine Glycine Threonine C
12、 O NH3 + CH O- CH2OH Serine hydroxymethyl transferase CH3CH O Acetaldehyde PLP Serine FH4-CH2 Methylene-tetrahydrofolate FH4 Tetrahydrofolate OH2 Serine dehydratase Serine hydroxy-methyl transferase PLP C O NH3 + CH O- CH3 C O OC O- CH3 Pyruvate OH2 OH2 NH4 + C O OC O- SCoA Acetyl CoA Pyruvate dehyd
13、rogenase CO2NAD+ NADH + H+ CoASH -KG Glu Alanine aminotransferase University of ManitobaAdam Burgener University of ManitobaAdam Burgener N N H N N NH glutamate O O NH2 NHCH2 H 5 10 N N H N N NH glutamate O O NH2 NHCH2 H H H N N H N N NH glutamate O O NH2 NHCH2 H H H H H NADPH + H+ NADP+ NADPH + H+
14、NADP+ Folate = F Dihydrofolate = FH2 Tetrahydrofolate = FH4 5 5 10 10 Dihydrofolate reductase Dihydrofolate reductase University of ManitobaAdam Burgener N N H N N NH glutamate O O NH2 NH CH2 H H H H H Serine Glycine Serine hydroxymethyl transferase FH4 5 10 5 10 CH2 N N H N N NH glutamate O O NH2 N
15、 CH2 H H H H N5, N10 - methylene FH4 OH2 NADP+ NADPH + H+ 5 10 CH N N H N+ N NH glutamate O O NH2 N CH2 H H H H N5, N10 - methenyl FH4 Donates formyl groups in purine biosynthesis pathway Methenyl FH4 reductase 5 10 OH2 CH N N H N H N NH glutamate O O NH2 N CH2 H H H H O N10 - Formyl FH4 Cycohydrola
16、se Involved in pyrimidine biosynthesis pathway, amino acid synthesis University of ManitobaAdam Burgener Phenylalanine NAD+ NADH + H+ Tetrahydrobiopterin Dihidrobiopterin OH2 O2 Phenylalanine hydroxylase Tyrosine O NH3 + O- O NH3 + OH O- C O CCH2 O OH O- p-Hydroxyphenyl pyruvate Tyrosine aminotransf
17、erase PLP -KG Glu O2 CO2 P-hydroxyphenylpyruvate dioxygenase CCH2 O OH OH O- Homogentisate Homogentisate 1,2-dioxygenase O2 H+ C CH2C C CCH2 O O- O CC O O- O H H Maleyl acetoacetate C CH2C C CCH2 O O- O C C O O- O H H Maleyl acetoacetate isomerase Fumaryl acetoacetate Fumaryl acetoacetase OH2 C CH3
18、C CH2 O O- O C C C C O O- O H H O-Fumarate Acetoacetate Succ Succ CoA Ketoacyl CoA transferase C CH3 C CH2 O SCoA O Acetoacetyl CoA a C4 fatty acid -keto acyl CoA thiolase (-oxidation pathway) C CH3 O SCoA 2 x Acetyl CoA TCA CYCLE University of ManitobaAdam Burgener C CH O NH3 + CH CH3CH3 O- Valine
19、Branched chain AA-transaminase -KG Glu C C O O CH CH3CH3 OH -keto isovalerate -ketoacyl dehydrogenase TPP, FAD CoASH NAD+ NADH + H+ CO2 SCoA CO CH CH3CH3 Isobutyryl CoA Acyl CoA dehydrogenase FAD FADH2 SCoA CO C CH3CH2 Methyl acrylyl CoA SCoA CO CH CH3CH2 OH OH2 Enoyl CoA hydratase -hydroxy isobutyr
20、yl CoA hydroxy isobutyryl CoA hydrolase CoASH O- CO CH CH3CH2 OH -hydroxyl -isobutyrate -hydroxy isobutyryl dehydrogenase NAD+ NADH + H+ O- CO CH CH3 CH O Methyl malonyl semi-aldehyde Methyl malonyl semi-aldehyde dehydrogenase NAD+ NADH + H+ CO2 SCoA C O CH2 CH3 CoASH Propionyl CoA (1) Propionyl CoA
21、 carboxylase (2) Methyl malonyl CoA epimerase (3) Methyl Malonyl CoA mutase SCoA C O CH2 CH2 C O- O Succinyl CoA OH2 PLP University of ManitobaAdam Burgener University of ManitobaAdam Burgener C O CHNH3 + CH3 O- C C O CH2 O CH2 C O- O- O Glutamate Alanine Pyruvate -KG C C O CH2 O CH2 CH O- O- NH3 +C
22、 O CO CH3 O- Alanine transaminase Transamination and deaminations involved in removal of amino group from an amino acid PLP University of ManitobaAdam Burgener Attaches to a lysine residue on the transaminase enzyme University of ManitobaAdam Burgener Amino acid Keto acid -KG Glutamate Build-up Glutamate C C O CH2 O CH2 CH O- O- NH3 + Glutamine synthetase NH3 ATP AD
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