12.09.08: Amino Acid Metabolism (Nitrogen Metabolism)

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12.09.08: Amino Acid Metabolism (Nitrogen Metabolism)

  1. 1. Author: Robert Lyons, Ph.D., 2008License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution – Share Alike 3.0 License:http://creativecommons.org/licenses/by-sa/3.0/We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use,share, and adapt it. The citation key on the following slide provides information about how you may share and adapt thismaterial.Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions,corrections, or clarification regarding the use of content.For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or areplacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to yourphysician if you have questions about your medical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  2. 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC §105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ{ Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  3. 3. M1 Renal: Nitrogen Metabolism (and Related Topics) • Amino Acid Metabolism (Nitrogen metabolism) • Folate Metabolism ( One-Carbon pathways ) • Nucleotide Metabolism Dr. Robert Lyons Assistant Professor, Biological Chemistry Director, DNA Sequencing Core Web: http://seqcore.brcf.med.umich.edu/mcb500 Fall 2008
  4. 4. R. Lyons Supplementary study material on the Web: http://seqcore.brcf.med.umich.edu/mcb500
  5. 5. Amino Acid metabolism Folate metabolism Amino acids Met Methylene Cycle Glu, Gln, THF Asp, NH 3 Urea oxaloacetate DNA P u rin e s P y rim id in e s RNA Uric Acid (energy) fumarate TCA Cycle Nucleic Acid metabolismR. Lyons
  6. 6. Protein Degradation: • Endogenous proteins degrade continuously - Damaged - Mis-folded - Un-needed • Dietary protein intake - mostly degraded Nitrogen Balance - expresses the patient s current status - are they gaining or losing net Nitrogen?
  7. 7. Transaminases Collect AminesGeneral reaction overview: H H (-) (-) (-) (-) R1 C COO +R2 C COO R1 C COO + R2 C COO O O NH2 NH2 !-keto amino acid !-keto amino acid (typically acid acid alpha-ketoglutarate) (typically glutamate)Details of reaction mechanism: amino !-keto acid acid H H+ (-) H R C COO (-) R C COO (-) (-) R C COO (-) O R C COO R C COO NH2 N + N N + NH2 O CH CH HCH HCH CH P OCH2 OH P OCH2 OH P OCH2 OH H2 O P OCH2 OH P OCH2 OH + CH3 CH3 + CH3 N N N + CH3 + H N N CH3 H H H H pyridoxamine pyridoxal phosphate phosphate R. Lyons
  8. 8. Transfer the amine back to an acceptor α-keto acid NH2 O CH H HCHP OCH2 OH (-) P OCH2 OH + R C COO + R C COO + + N CH3 O N CH3 NH2 H H pyridoxamine !-keto pyridoxal amino phosphate acid phosphate acid R. Lyons
  9. 9. In peripheral tissues, transaminases tend to form Glutamate when they catabolize amino acids In other words, alpha-ketoglutarate is the preferred acceptor, and Glutamate is the resulting amino acid: Some amino acid + α-ketoglutarate à some alpha keto acid + Glutamate
  10. 10. Glutamate can donate its amines to form other amino acids as needed A specific example - production of Aspartate in liver (described a few slides from now): Glutamate + oxaloacetate à α-ketoglutarate + aspartate
  11. 11. G e tt in g A m in es In to the L iv e r NAD(P) H Glutamate O2C CH2CH2C CO(-) (-) O2C CH2CH2C CO(-) (-) 2 + NH3 2Dehydrogenase: (mito) O NH2 glutamat e NAD(P)H !-ketogluta rate ammonia H H (-) O (-) (-) Glutamine OOC C CH CH2 COO 2 OOC C CH2CH2C Synthetase: NH3 NH3 NH2 (+) (+) ATP+ NH3 ADP+ Pi glutamate glutamine R. Lyons
  12. 12. . In th e L iv er: Pre curs ers fo r U rea C ycle Glutamine is hydrolyzed to glutamate and ammonia: H H (-) O O (-) OOC C CH2CH2C OOC C CH2CH C 2 NH OH NH3 2 NH3 (+) (+) H2O glutamine NH3 glutamate Ammonia can also be formed by the glutamate dehydrogenase reaction and several other reactions as well. Glutamate donates its amino group to form aspartate: Glutamate-aspartate aminotransferase: H H H (- ) O 2C CH2 CH2 C CO(-) 2 + ( -) O 2CC H2 C CO(2-) (- ) O 2C CH2 CH2 C C O(-) 2 + (- ) O 2C CH 2 C CO(-) 2 N H2 O O NH2 Glutamate oxaloacetate !-keto aspartate glutarate .R. Lyons
  13. 13. 2ATP + HCO3 + NH3 Carbamoyl phosphate 1 O (-) NH2 C OPO Pi 3 2 2ADP + Pi H H O (-) (+) (-) OOC C CH2CH2CH2NH3 OOC C CH2CH CH NH C NH2 2 2 NH3 NH3 (+) (+) Ornithine Citrulline Liver mitochondrion Liver cytoplasm H H O (-) (-) (+) OOC C CH2CH2CH2NH C NH2 OOC C CH2CH CH2NH3 2 NH3 NH3 (+) Citrulline Ornithine (+) O H NH2 C NH2 ATP (-) O2CCH2 C CO(-) 2 Urea NH2 5 3 aspartate H2O AMP + PP i H H (-) (-) O2CCH2C CO(-) 2 OOC C CH2CH2CH2NH C NH2 H NH2 NH NH2 (-) (+) 3 (+) OOC C CH CH2CH2NH C NH(+) 2 2 Arginine NH3 Argininosuccinate (+) 4 (-) H (-) O2C C C CO2 H FumarateR. Lyons
  14. 14. C a rb a m o y l p h o s p h a t e sy n th e ta s e I ATP NH ATP 3 O O O O (- ) NH HO C O HO C O P HO C NH P O C 2 2 c ar bo ny l ca rb a mo ylb ic ar b on at e ca rb a ma te ADP ph os p ha te Pi ADP ph os p ha te R. Lyons
  15. 15. O r n it h in e T r a n s c a r b a m o y la s e C arb am o y l p ho s p hat e O Pi ( -) N H2 C O P O3 H H O ( -) (+ ) (- ) OO C C C H C H2 C H N H 3 OOC C C H 2C H2 C H2 N H C NH 2 2 2 NH NH 3 (+ ) 3 (+ ) O r n ith in e C it r u llin eR. Lyons
  16. 16. A r g in in o s u c c in a t e s y n t h e t a s e H (-) (-) O2CC 2C CO2 H NH2 H aspartate (-) O2CCH2C CO(-) 2 H O H NH2(-) OOC C CH2CH2CH NH C NH (-) (+) 2 2 OOC C CH2CH2CH2NH C NH2 NH3 (+) Citrulline NH3 (+) Argininosuccinate ATP AMP + PPi R. Lyons
  17. 17. A r g in in o s u c c in a t e ly a s e H (-) (-) O2CCH2C CO2 H NH2 H(-) (+) (-) OOC C CH CH2CH2NH C NH2 OOC C CH CH2CH2NH C NH2 2 2 NH NH NH2 3 (+) (+) 3 (+) Argininosuccinate (-) H (-) Arginine O2C C C CO2 H Fumarate R. Lyons
  18. 18. A r g in a s e H H(-) (-) (+) OOC C CH CH2CH2NH C NH2 2 OOC C CH2CH2CH2NH3 NH NH2 NH (+)3 (+) (+) 3 Ornithine H2O O Arginine NH2 C NH2 Urea R. Lyons
  19. 19. 2ATP + HCO3 + NH3 Carbamoyl phosphate 1 O (-) NH2 C OPO Pi 3 2 2ADP + Pi H H O (-) (+) (-) OOC C CH2CH2CH2NH3 OOC C CH2CH CH NH C NH2 2 2 NH3 NH3 (+) (+) Ornithine Citrulline Liver mitochondrion Liver cytoplasm H H O (-) (-) (+) OOC C CH2CH2CH2NH C NH2 OOC C CH2CH CH2NH3 2 NH3 NH3 (+) Citrulline Ornithine (+) O H NH2 C NH2 ATP (-) O2CCH2 C CO(-) 2 Urea NH2 5 3 aspartate H2O AMP + PP i H H (-) (-) O2CCH2C CO(-) 2 OOC C CH2CH2CH2NH C NH2 H NH2 NH NH2 (-) (+) 3 (+) OOC C CH CH2CH2NH C NH(+) 2 2 Arginine NH3 Argininosuccinate (+) 4 (-) H (-) O2C C C CO2 H FumarateR. Lyons
  20. 20. Urea Cycle Connects to TCA Cycle H (-) O2CCH2C CO(-) 2 Ornithine Citrulline NH2 AspartateUrea Urea Cycle Arginine Argininosuccinate Oxaloacetate Malate H (-) (-) O2C C C CO2 H TCA Cycle Citrate Fumarate !-Ketoglutarate R. Lyons
  21. 21. G e tt in g A m in es In to the L iv e r NAD(P) H Glutamate O2C CH2CH2C CO(-) (-) O2C CH2CH2C CO(-) (-) 2 + NH3 2Dehydrogenase: (mito) O NH2 glutamat e NAD(P)H !-ketogluta rate ammonia H H (-) O (-) (-) Glutamine OOC C CH CH2 COO 2 OOC C CH2CH2C Synthetase: NH3 NH3 NH2 (+) (+) ATP+ NH3 ADP+ Pi glutamate glutamine R. Lyons
  22. 22. 2ATP + HCO3 + NH3 Carbamoyl phosphate 1 O (-) NH2 C OPO Pi 3 2 2ADP + Pi H H O (-) (+) (-) OOC C CH2CH2CH2NH3 OOC C CH2CH CH NH C NH2 2 2 NH3 NH3 (+) (+) Ornithine Citrulline Liver mitochondrion Liver cytoplasm H H O (-) (-) (+) OOC C CH2CH2CH2NH C NH2 OOC C CH2CH CH2NH3 2 NH3 NH3 (+) Citrulline Ornithine (+) O H NH2 C NH2 ATP (-) O2CCH2 C CO(-) 2 Urea NH2 5 3 aspartate H2O AMP + PP i H H (-) (-) O2CCH2C CO(-) 2 OOC C CH2CH2CH2NH C NH2 H NH2 NH NH2 (-) (+) 3 (+) OOC C CH CH2CH2NH C NH(+) 2 2 Arginine NH3 Argininosuccinate (+) 4 (-) H (-) O2C C C CO2 H FumarateR. Lyons
  23. 23. C P S I is S t im u la t e d b y N A G H (-) O H N -a c e t y l OOC C CH CH C 2 2 OH (-) O g lu t a m a t e NH OOC C CH CH C 2 2 + Co A - C O s y n th e tas e OH C O N H3 C H3 ( +) C H3 N - a c e t y l g lu t a m a te g lu t a m a t e a cetyl Co A (N A G )( r e p e a t in g t h e f ig u r e f r o m p a g e 3 o f y o u r h a n d o u t ) ATP NH ATP 3 O O O O ( -) HO C O HO C O P HO C NH P O C NH 2 2 c a rb on y l c ar ba m oy l bi ca rb o na te c ar ba m at e ADP p ho s ph at e Pi ADP p ho sp h at e R. Lyons
  24. 24. -- Muscle (Amines) Glucose Pyruvate Glutamate Amino acids !-ketoglutarate Alanine blood transport Alanine !-ketoglutarate Urea Glutamate NH3 Glucose Pyruvate LiverR. Lyons
  25. 25. Complicating the picture: Other tissues may be involved Muscle: Amino acids: purine Transamination Deamination deamination: (+) Alanine Glutamate NH4 Glutamine Intestine: Glutamine (+) Alanine NH4 Citrulline Glutamine Kidney: Citrulline NH 3 (+) Arginine NH4 Liver: Glutamine Arginine (+) Alanine NH4 Urea Glu AspartateR. Lyons
  26. 26. Why is Ammonia Toxic?
  27. 27. Why is Ammonia Toxic? • Possible neurotoxic effects on glutamate levels (and also GABA) (due to shifting equilibria of reactions involving these compounds)
  28. 28. Why is Ammonia Toxic? • Possible neurotoxic effects on glutamate levels (and also GABA) (due to shifting equilibria of reactions involving these compounds) • Possible metabolic/energetics effects: - alpha-ketoglutarate levels - glutamate levels - glutamine
  29. 29. 2ATP + HCO3 + NH3 Carbamoyl phosphate 1 O (-) NH2 C OPO Pi 3 2 2ADP + Pi H H O (-) (+) (-) OOC C CH2CH2CH2NH3 OOC C CH2CH CH NH C NH2 2 2 NH3 NH3 (+) (+) Ornithine Citrulline Liver mitochondrion Liver cytoplasm H H O (-) (-) (+) OOC C CH2CH2CH2NH C NH2 OOC C CH2CH CH2NH3 2 NH3 NH3 (+) Citrulline Ornithine (+) O H NH2 C NH2 ATP (-) O2CCH2 C CO(-) 2 Urea NH2 5 3 aspartate H2O AMP + PP i H H (-) (-) O2CCH2C CO(-) 2 OOC C CH2CH2CH2NH C NH2 H NH2 NH NH2 (-) (+) 3 (+) OOC C CH CH2CH2NH C NH(+) 2 2 Arginine NH3 Argininosuccinate (+) 4 (-) H (-) O2C C C CO2 H FumarateR. Lyons
  30. 30. Inherited Defects of Urea Cycle Enzymes: Diagnosis Defects are diagnosed based on the metabolites seen in the blood and/or urine. CPSD No elevation except ammonia; diagnosed by elimination. OTCD Elevated CP causes synthesis of Orotate ASD Elevated citrulline ALD Elevated argininosuccinate AD Elevated arginine
  31. 31. 2ATP + HCO3 + NH3 Carbamoyl phosphate 1 O (-) NH2 C OPO Pi 3 2 2ADP + Pi H H O (-) (+) (-) OOC C CH2CH2CH2NH3 OOC C CH2CH CH NH C NH2 2 2 NH3 NH3 (+) (+) Ornithine Citrulline Liver mitochondrion Liver cytoplasm H H O (-) (-) (+) OOC C CH2CH2CH2NH C NH2 OOC C CH2CH CH2NH3 2 NH3 NH3 (+) Citrulline Ornithine (+) O H NH2 C NH2 ATP (-) O2CCH2 C CO(-) 2 Urea NH2 5 3 aspartate H2O AMP + PP i H H (-) (-) O2CCH2C CO(-) 2 OOC C CH2CH2CH2NH C NH2 H NH2 NH NH2 (-) (+) 3 (+) OOC C CH CH2CH2NH C NH(+) 2 2 Arginine NH3 Argininosuccinate (+) 4 (-) H (-) O2C C C CO2 H FumarateR. Lyons
  32. 32. C P S I is S t im u la t e d b y N A G H (-) O H N -a c e t y l OOC C CH CH C 2 2 OH (-) O g lu t a m a t e NH OOC C CH CH C 2 2 + Co A - C O s y n th e tas e OH C O N H3 C H3 ( +) C H3 N - a c e t y l g lu t a m a te g lu t a m a t e a cetyl Co A (N A G )( r e p e a t in g t h e f ig u r e f r o m p a g e 3 o f y o u r h a n d o u t ) ATP NH ATP 3 O O O O ( -) HO C O HO C O P HO C NH P O C NH 2 2 c a rb on y l c ar ba m oy l bi ca rb o na te c ar ba m at e ADP p ho s ph at e Pi ADP p ho sp h at e R. Lyons
  33. 33. 2ATP + HCO3 + NH3 Carbamoyl phosphate 1 O (-) NH2 C OPO Pi 3 2 2ADP + Pi H H O (-) (+) (-) OOC C CH2CH2CH2NH3 OOC C CH2CH CH NH C NH2 2 2 NH3 NH3 (+) (+) Ornithine Citrulline Liver mitochondrion Liver cytoplasm H H O (-) (-) (+) OOC C CH2CH2CH2NH C NH2 OOC C CH2CH CH2NH3 2 NH3 NH3 (+) Citrulline Ornithine (+) O H NH2 C NH2 ATP (-) O2CCH2 C CO(-) 2 Urea NH2 5 3 aspartate H2O AMP + PP i H H (-) (-) O2CCH2C CO(-) 2 OOC C CH2CH2CH2NH C NH2 H NH2 NH NH2 (-) (+) 3 (+) OOC C CH CH2CH2NH C NH(+) 2 2 Arginine NH3 Argininosuccinate (+) 4 (-) H (-) O2C C C CO2 H FumarateR. Lyons
  34. 34. Clinical Management of Urea Cycle Defects • Dialysis to remove ammonia • Provide the patient with alternative ways to excrete nitrogenous compounds: * Intravenous sodium benzoate or phenylacetate * Supplemental arginine c am yl p o h arb o h sp ate Excreted by kidney O ith e rn in C llin itru e O NH C NH2 AP T A rta spa te Urea 2 ASD X +PP i AP M HO 2 A in rgin e A in o cc ate rg in su in Excreted by kidney D ry ieta A in e rg in ALD X R. Lyons• Levulose - acidifies the gut • Low protein diet
  35. 35. Degrading the Amino Acid Carbon Backbone
  36. 36. Easily-degraded products after transamination: H (-) (-) (-) (-) O2C CH2C CO2 O2CCH2C CO2 NH3 transamination O (+) aspartate oxaloacetate H (-) (-) (-) (-) O2C CH2CH2C CO2 O2C CH2 2C CO2 CH NH3 transamination O (+) glutamate !-ketoglutarate H (-) CH3 C CO2 CH3 C CO(-) 2 NH3 transamination O (+) alanine pyruvate R. LyonsWe also already know how to degrade Glutamine: glutaminase Glutamine ----------------> glutamate + ammonia …and by analogy, how to degrade Asparagine: asparaginase Asparagine ---------------> aspartate + ammonia
  37. 37. Amino Acids are categorized as Glucogenic or ketogenic or both. Many amino acids are purely glucogenic: Glutamate, aspartate, alanine, glutamine, asparagine,… Some amino acids are both gluco- and ketogenic: Threonine, isoleucine, phenylalanine, tyrosine, tryptophan The only PURELY ketogenic Amino Acids: leucine, lysine
  38. 38. H (-) OOC C CH2CH2CH2NH C NH2 NH3 NH2 (+) (+) Arginine Urea (via the urea cycle) H (-) (+) OOC C CH2CH2CH2NH3 NH3Amino acids with 5-carbon (+) Ornithine !-ketoglutaratebackbones tend to form α ketoglutarate glutamate H (-) (-) O OOC (+) OOC C CH2CH2C N H H NH3 Proline (+) glutamate - 5 - semialdehyde (+) NAD(P) NAD(P)H H H O O (-) (-) OOC C CH2CH2C OOC C CH2CH2C OH NH2 NH3 NH3 (+) (+) glutamate NH3 H2O glutamine ! - ketoglutarate R. Lyons
  39. 39. Degradation and Biosynthesis of Serine and Glycine (+) NAD NADH H (-) (+) Glycine OOC C NH3 (+) CO2 + NH4 Synthase: H Glycine THF N5 -N10- methylene THF (-) Serine (-) OOC CH NH3 OOC C 2 NH3 (+)Hydroxymethyl- (+) H CH2OH transferase: Serine Glycine 10 THF N5 -N - methylene THF H 2O (+) NH4 Serine (-) (-) OOC C NH3 (+) (-) OOC C NH2 (+) (-) OOC CH NH3 OOC C O Dehydratase: (+) CH2OH CH2 CH3 CH3 H 2O Serine R. Lyons
  40. 40. H H (+) (-) CH3 S CH2 CH C COO (-) 2 CH3 S CH2 CH C 2 COO CH2 NH (+) 3 NH3 (+) ATP + PPi + O H2O Adenine Pi H H Methionine H OH OH H S-Adenosyl Methionine Methyl a cceptor tetrahydrofolate Bios ynthetic * Methylation see examples reaction N5 methyl Methylated acceptor tetrahydrofolateMethionine Cycle H (+) HS CH2 CH C 2 H COO (-) And Biological HS CH2 CH2 C NH3 COO (-) CH2 NH (+) 3 O Methyl Groups (+) Homocysteine H H OH OH H H Adenine H S-Adenosyl Homocysteine (-) HO CH C 2 COO NH (+) 3 Serine H (-) HS CH2 C COO NH (+) 3 Cysteine (remainder of homocysteine degraded for energy) R. Lyons
  41. 41. Phenylalanine and Tyrosine (Normal path shown in black, pathological reaction shown in red) Tetrahydrobiopterin + O2 (+) (+) Dihydrobiopterin + H2O NH 3 NH 3 (-) (-) CH2 CH COO HO CH2 CH COO Enzyme: Phenylalanine Phenylalanine Tyrosine hydroxylase Phenylketonuria (no phenylalanine hydroxylase) Homogentisate Deficiency: Enzyme: O Alkaptonuria homogentisate (-) Ochronosis dioxygenase CH2 C COO (you don’t need to Phenylpyruvate know the rest)R. Lyons
  42. 42. Branched Chain Amino Acids Isoleucine Leucine Valine (-) (-) (-) CH3 CH2 CH CH COO CH3CH CH 2 CH COO CH3 CH CH COO CH3 NH3 CH3 NH3 CH3 NH3 (+) (+) (+ ) !"KG !"KG !"KG ---------------- Transamination ---------------- Glu Glu Glu (-) (-) (-) CH3 CH2 CH C COO CH3CHCH 2 C COO CH3CH C COO CH3 O CH3 O CH3 O + + + NAD, CoASH NAD, CoASH NAD, CoASH --- Branched-chain !-keto acid dehydrogenase --- NADH + 2 NADH + CO2 NADH + CO2 CO CH3 CH2 CH C S-CoA CH3CHCH 2 C S-CoA CH3CH C S-CoA CH3 O CH3 O CH3 O (continues on to degradation path similar to #-oxidation of fatty acids)R. Lyons
  43. 43. Synthesis of Bioactive Amines (+) (+) NH 3 HO NH 3 (-) (-)HO CH 2 CH COO HO CH 2 CH COO Tyrosine Tyrosine hydroxylase Dihydroxyphenylalanine (L-DOPA) HO HO HO (+) OH (+) OHHO CH 2CH 2NH 3 HO CH CH 2NH 3 HO CHCH 2 N CH 3 H H H Dopamine Norepinephrine Epinephrine R. Lyons
  44. 44. Synthesis of Bioactive Amines (-) HO (-) CH 2 CH COO CH2 CH COO N NH3 Tryptophan N NH (+) hydroxylase (+) 3 Tryptophan 5-hydroxytryptophan PLP-dependent decvarboxylation CO2 HO NAD+ CH 2 CH2 NH3 (+) N SerotoninR. Lyons
  45. 45. Synthesis of Bioactive Amines (-) (-) (-) COO CH 2 CH2 CH COO NH COO CH 2 CH 2 CH2 (+) 3 Glutamate NH3 decarboxylase (+) Glutamate (PLP-dependent ) !-aminobutyric acid (GABA) N (- N CH2 CH COO ) CH2 CH2 NH3 (+) N Histidine N H NH decarboxylase H (+) 3 (PLP-dependent ) Histidine HistamineR. Lyons
  46. 46. NON-Essential Amino Acids: Glutamate, aspartate, alanine, glutamine, asparagine, (proline), glycine, serine (cysteine, tyrosine) Essential Amino Acids: Arginine (!), phenylalanine, methionine, histidine, Isoleucine, leucine, valine, threonine, tryptophan, lysine
  47. 47. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicySlide 4: Robert LyonsSlide 5: Robert LyonsSlide 7: Robert LyonsSlide 8: Robert LyonsSlide 11: Robert LyonsSlide 12: Robert LyonsSlide 13: Robert LyonsSlide 14: Robert LyonsSlide 15: Robert LyonsSlide 16: Robert LyonsSlide 17: Robert LyonsSlide 18: Robert LyonsSlide 19: Robert LyonsSlide 20: Robert LyonsSlide 21: Robert LyonsSlide 22: Robert LyonsSlide 23: Robert LyonsSlide 24: Robert LyonsSlide 25: Robert LyonsSlide 29: Robert LyonsSlide 31: Robert LyonsSlide 32: Robert LyonsSlide 33: Robert LyonsSlide 34: Robert LyonsSlide 36: Robert LyonsSlide 38: Robert LyonsSlide 39: Robert LyonsSlide 40: Robert LyonsSlide 41: Robert LyonsSlide 44: Robert LyonsSlide 45: Robert Lyons

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