Flashcards in Lecture 47 Deck (44)
What are three types of amino acids that can be catabolized for use of their carbon skeletons?
Amino acids can be classified as glucogenic, ketogenic, or both, based on which of the 7 intermediates are produced during their catabolism
What are the nonessential glucogenic amino acids?
Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline, & Serine
What are nonessential ketogenic amino acids?
What are nonessential ketogenic & glucogenic amino acids?
What are essential glucogenic amino acids?
Histidine, Methionine, Threonine, & Valine
What are essential ketogenic amino acids?
Leucine & Lysine
What are essential ketogenic & glucogenic amino acids?
Isoleucine, Phenyl-alanine, & tryptophan
Can some amino acids be conditionally essential?
Yes. For example, supplementation with glutamine & arginine has been shown to improve outcomes in patients with trauma, postoperative infections, & immunosuppression
How are asparagine and aspartate metabolized to form oxaloacetate?
1) Asparagine --> Aspartate (uses Asparaginase)
2) Aspartate + alpha-ketoglutarate --> Glutamate + Oxaloacetate (uses Aspartate aminotransferase)
What is lacking in leukemia cells and how can leukemic patients be treated?
1) Some leukemia cells are unable to synthesize sufficient asparagine to support their growth
2) Asparaginase can be administered systemically to treat leukemic patients
What are 7 intermediate products that are formed as byproducts of catabolism of carbon skeletons of amino acids?
2) Acetyl CoA
6) Succinyl CoA
What is the process by which histidine is degraded to form alpha-ketoglutarate via glutamate?
1) Histidine --> Urocanic acid (uses histidase)
2) Urocanic acid --> N-Formimino-glutamate (FlGlu)
3) N-Formimino-glutamate (FlGlue) + Tetrahydro-folate --> Glutamate + N5-Formimino-tetrahydrofolate
4) Glutamate --> alpha-ketoglutarate
How is alanine transaminated to form pyruvate?
L-Alanine + alpha-ketoglutarate --> Pyruvate + Glutamate (uses Alanine aminotransferase [Pyridoxal phosphate (PLP)])
What is Pyridoxal phosphate (PLP)?
1) Pyridoxal-phosphate (PLP) is a prosthetic group of certain enzymes
2) PLP is also the active form of vitamin B6
3) This co-factor acts as an electron sink to stabilize carbanionic intermediates in both substitution and elimination reactions involving aminated compounds
4) It is a co-factor of Alanine aminotransferase
How is phenylalanine degraded to form tyrosine, and then fumarate & acetoacetate
1) L-Phenylalanine + Tetrahydro-biopterin + O2 --> L-Tyrosine + Dihydro-biopterin + H2O (uses Phenylalanine hydroxylase)
2) L-tyrosine --> Fumarate
3) L-tyrosine --> Acetoacetate
How can Methionine be degraded or reformed?
1) Using methyltransferases, L-methionine can be demethylated to form L-homocysteine and release adenosine in the process
2) L-homocysteine can then be further degraded to form L-cysteine
3) L-homocysteine can also use methionine synthase to reform L-methionine (methylation)
What cofactors are required to form methionine and cysteine?
1) Conversion to methionine requires folate & vitamin B12-derived coenzymes (this is a remethylation process)
2) Formation of cysteine requires vitamin B6 (pyridoxine), and is a transsulfuration process - the sulfur of methionine becomes the sulfur of cysteine
Describe the degradation of leucine
1) Leucine is transaminated to form alpha-ketoiso-caproic acid
2) Alpha-ketoiso-caproic acid undergoes oxidative decarboxylation to form Isovaleryl CoA
3) Isovaleryl CoA undergoes FAD-linked Dehydrogenation to form Beta-methyl-crotonyl CoA
4) Beta-methyl-crotonyl CoA eventually forms HMG CoA and then acetoacetate + acetyl CoA
Describe the degradation of valine
1) Valine is transaminated to form alpha-ketoiso-valeric acid
2) alpha-ketoiso-valeric acid undergoes Oxidative decarboxylation to form isobutyryl CoA
3) Isobutyryl CoA undergoes FAD-linked dehydrogenation to form propionyl CoA
4) Propionyl CoA eventually forms Succinyl CoA
Describe the degradation of isoleucine
1) Isoleucine is transaminated to form alpha-keto-beta-methyl-valeric acid
2) alpha-keto-beta-methyl-valeric acid undergoes oxidative decarboxylation to form alpha-methyl-butyryl CoA
3) alpha-methyl-butyryl CoA undergoes FAD-linked dehydrogenation to form propionyl CoA
4) Propionyl CoA eventually forms succinyl CoA
What becomes deficient in maple syrup urine disease?
Oxidative decarboxylation of branched-chain amino acids is deficient in maple syrup urine disease
How are alanine, aspartate, & glutamate formed with their corresponding alpha-keto acids?
1) Pyruvate + Amino acid --> alpha-keto acid + alanine
2) Oxaloacetate + amino acid --> Aspartate + alpha-keto acid
3) alpha-ketoglutarate + amino acid --> Glutamate + alpha-keto acid
4) Each of the above reactions uses an aminotransferase with PLP
Describe the formation of dopamine from tyrosine
1) Tyrosine + Tetrahydro-biopterin + O2 --> 3,4-Dihydroxy-phenylalanine (DOPA) + Dihydro-biopterin + H2O (uses Tyrosine hydroxylase - rate limiting step)
2) 3,4-Dihydroxy-phenylalanine (DOPA) --> Dopamine (uses aromatic amino acid decarboxylase; releases CO2)
Describe the formation of Norepinephrine from Dopmaine
Dopamine + Ascorbate + O2 --> Norepinephrine + Dehydro-ascorbate + H2O (Uses Dopamine beta-hydroxylase with a Cu2+ as a cofactor)
Describe the formation of epinephrine from norepinephrine
Norepinephrine + S-Adenosyl-methionine --> S-Adenosyl-homocysteine + Epinephrine (uses phenylethanolamine-N-methyl-transferase)
What does cocaine do?
Cocaine inhibits dopamine and norepinephrine reuptake in the brain
What is Parkinson disease?
1) Common neurodegenerative movement disorder affecting 1 million people in the US
2) Symptoms: paucity of spontaneous movement, tremor at rest, muscle rigidity, shuffling gait, mask-like facial expression, autonomic disturbances, depression, & cognitive impairment
3) Results from degeneration of dopamine neurons in the substantia nigra pars compacta
4) Oral administration of L-DOPA was found beneficial but effects diminish after 5 years
Why is L-DOPA given to patients with parkinsons disease rather than direct dopamine?
L-DOPA can cross the blood-brain barrier, while dopamine cannot
Can parkinsons disease be inherited?
Yes. There are five nuclear genes that are known to carry mutations that cause rare inherited forms (<10%) of Parkinson disease
How are epinephrine and norepinephrine metabolized?
Metabolism of the catecholamines (epinephrine & norepinephrine) uses catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO) to form Vanillylmandelic acid (VMA)
How is dopamine metabolized?
Metabolism of the catecholamine (dopamine) uses catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO) to form Homovanillic acid (VMA)
What were antidepressants first made from?
Monoamine oxidase (MAO) inhibitors?
How is serotonin produced?
1) Tryptophan + Tetrahydro-biopterin --> 5-Hydroxy-tryptophan + Dihydro-biopterin + H2O (uses hydroxylase)
2) 5-hydroxy-tryptophan --> Serotonin + CO2 (uses Aromatic amino acid decarboxylase with PLP)
What is formed when serotonin is degraded by monoamine oxidase (MAO)?
Hydroxyindole acetic acid
What does the antidepressant Fluoxetine (Prozac) do?
It inhibits serotonin reuptake
How is GABA (gamma-aminobutyrate) formed?
Glutamate --> GABA + CO2 (uses glutamate decarboxylase with PLP)
How does glutamate work?
1) Glutamate acts via ionotropic (Na+, Ca2+) and metabotropic (GPCR) recepors
2) Glutamate is the major excitatory neurotransmitter in human brain
3) Chronic release can lead to excitotoxicity
How does GABA work?
1) GABA acts via ionotropic (Cl-) and metabotropic (GPCR) receptors
2) It is the major inhibitory neurotransmitter in the brain
How is histamine formed?
Histidine --> Histamine + CO2 (uses histidine decarboxylase with PLP)
What does histamine do?
Histamine is a chemical messenger that mediates allergic and inflammatory reactions and gastric acid secretion
How is melatonin formed?
1) Serotonin + AcCoa --> N-acetylserotonin + CoASH (uses AANAT)
2) N-acetylserotonin --> Melatonin (uses HIOMT)
What accounts for melatonin formation?
While levels of HIOMT activity remain fairly constant, the daily rhythm in melatonin synthesis is generated by a concurrent rhythm in AANAT activity
Describe the synthesis of creatine
1) Arginine + Glycine --> Guanidinoacetate + Ornithine (uses Amidino-transferase)
2) Guanidinoacetate + S-Adenosylmethionine --> S-Adenosylhomocysteine + Creatine (uses methyltransferase)