L-DOPA - Misplaced Pages

This is an old revision of this page, as edited by 202.92.35.71 (talk) at 00:57, 17 November 2011 (→Therapeutic use - hyperdopaminergia is a keyword that should have its own page). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Revision as of 00:57, 17 November 2011 by 202.92.35.71 (talk) (→Therapeutic use - hyperdopaminergia is a keyword that should have its own page)(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff) Pharmaceutical compound

L-DOPA
Clinical data


Pregnancy category	AU: B3
Routes of administration	oral
ATC code	N04BA01 (WHO)
Legal status
Legal status	In general: Over-the-counter (OTC)
Pharmacokinetic data
Bioavailability	30%
Metabolism	Aromatic-L-amino-acid decarboxylase
Elimination half-life	0.75–1.5 hours
Excretion	renal 70–80%
Identifiers
IUPAC name (S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid
CAS Number	59-92-7
PubChem CID	6047
DrugBank	APRD00309
ChemSpider	5824
UNII	46627O600J
KEGG	D00059
ChEBI	CHEBI:15765
ChEMBL	ChEMBL1009
CompTox Dashboard (EPA)	DTXSID9023209
ECHA InfoCard	100.000.405
Chemical and physical data
Formula	C₉H₁₁NO₄
Molar mass	197.19 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES O=C(O)(N)Cc1cc(O)c(O)cc1
InChI InChI=1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1 Key:WTDRDQBEARUVNC-LURJTMIESA-N
(what is this?) (verify)

L-DOPA (L-3,4-dihydroxyphenylalanine) is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline) collectively known as catecholamines. L-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc.). As a drug it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.

Therapeutic use

L-DOPA crosses the protective blood-brain barrier, whereas dopamine itself cannot. Thus, L-DOPA is used to increase dopamine concentrations in the treatment of Parkinson's disease and dopamine-responsive dystonia. This treatment was originally developed by George Cotzias and his coworkers. Once L-DOPA has entered the central nervous system, it is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase (DDC). Pyridoxal phosphate (vitamin B6) is a required cofactor in this reaction, and may occasionally be administered along with L-DOPA, usually in the form of pyridoxine.

Besides the CNS, L-DOPA is also converted into dopamine from within the peripheral nervous system. The resulting hyperdopaminergia causes many of the adverse side effects seen with sole L-DOPA administration. In order to bypass these effects, it is standard clinical practice to co-administer (with L-DOPA) a peripheral DOPA decarboxylase inhibitor (DDCI) such as carbidopa (medicines combining L-DOPA and carbidopa are branded as Lodosyn, Sinemet, Parcopa, Atamet, Stalevo) or with a benserazide (combination medicines are branded Madopar, Prolopa), to prevent the peripheral synthesis of dopamine from L-DOPA. Co-administration of pyridoxine without a DDCI accelerates the peripheral decarboxylation of L-DOPA to such an extent that it negates the effects of L-DOPA administration, a phenomenon that historically caused great confusion.

In addition, L-DOPA, co-administered with a peripheral DDCI, has been investigated as a potential treatment for restless leg syndrome. However, studies have demonstrated "no clear picture of reduced symptoms".

There are two types of response seen with administration of L-DOPA:

Short-duration response, which is related to the half-life of the drug
Longer-duration response, which depends on the accumulation of effects over at least two weeks. This response is evident only in early therapy, as the inability of the brain to store dopamine is not yet a concern.

Dietary supplements

Herbal extracts containing L-DOPA are available. The most common plant source of L-DOPA marketed in this manner is Mucuna pruriens (Velvet Bean).

Biological role

L-DOPA is produced from the amino acid L-tyrosine by the enzyme tyrosine hydroxylase (TH). It is also the precursor for the monoamine or catecholamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of L-DOPA.

L-DOPA can be directly metabolized by catechol-O-methyl transferase (COMT) to 3-O-methyldopa (3-OMD), and then further to vanillactic acid (VLA). This metabolic pathway is non-existent in the healthy body, but becomes important after peripheral L-DOPA administration in patients with PD or in the rare cases of patients with aromatic L-amino acid decarboxylase (AADC) enzyme deficiency.

The prefix L- references its property of levorotation (compared with dextrorotation or D-DOPA).

L-Phenylalanine, L-tyrosine, and L-DOPA, are all are precursors to the biological pigment melanin. The enzyme tyrosinase catalyzes the oxidation of L-DOPA to the reactive intermediate dopaquinone, which reacts further, eventually leading to melanin oligomers.

Side effects

The side effects of L-DOPA may include, but not limited to:

Hypotension, especially if the dosage is too high
Arrhythmias, although these are uncommon
Nausea, which is often reduced by taking the drug with food, although protein interferes with drug absorption
Gastrointestinal bleeding
Disturbed respiration, which is not always harmful, and can actually benefit patients with upper airway obstruction
Hair loss
Disorientation and confusion
Extreme emotional states, particularly anxiety, but also excessive libido
Vivid dreams and/or insomnia
Auditory and/or visual hallucinations
Effects on learning; there is some evidence that it improves working memory, while impairing other complex functions
Somnolence and narcolepsy
A condition similar to stimulant psychosis

Although there are many adverse effects associated with L-DOPA, in particular psychiatric ones, it has fewer than other antiparkinsonian agents, such as anticholinergics and dopamine receptor agonists.

More serious are the effects of chronic levodopa administration in the treatment of Parkinson disease, which include:

End-of-dose deterioration of function
On/off oscillations
Freezing during movement
Dose failure (drug resistance)
Dyskinesia at peak dose
Possible serotonin depletion: Recent studies have demonstrated that use of L-DOPA without simultaneously giving proper levels of serotonin precursors depletes serotonin
Possible dopamine dysregulation: The long-term use of L-DOPA in PD has been linked to the so-called dopamine dysregulation syndrome.

Clinicians will try to avoid these side effects by limiting L-DOPA doses as much as possible until absolutely necessary.

Toxicity

Some scientific studies suggest a cytotoxic role in the promotion and occurrence of adverse effects associated with L-DOPA treatment. Though the drug is generally safe in humans, some researchers have reported an increase in cytotoxicity markers in rat pheochromocytoma PC12 cell lines treated with L-DOPA. Other authors have attributed the observed toxic effects of L-DOPA in neural dopamine cell lines to enhanced formation of quinones through increased auto-oxidation and subsequent cell death in mesencephalic cell cultures. Though L-DOPA is generally considered safe, some controversy surrounds its use in the treatment of PD, given some data indicating a deleterious effect on intracellular and neuronal tissue involved in the pathogenesis of the disease.

History

In work that earned him a Nobel Prize in 2000, Swedish scientist Arvid Carlsson first showed in the 1950s that administering L-DOPA to animals with Parkinsonian symptoms would cause a reduction in their intensity. This treatment was later extended to manganese poisoning and later Parkinsonism by George Cotzias and his coworkers, who greatly increased the dose. The neurologist Oliver Sacks describes this treatment in human patients with encephalitis lethargica in his book Awakenings, upon which the movie of the same name is based.

The 2001 Nobel Prize in Chemistry was also related to L-DOPA: the Nobel Committee awarded one-fourth of the prize to William S. Knowles for his work on chirally catalysed hydrogenation reactions, the most noted example of which was used for the synthesis of L-DOPA:

Marine adhesion

L-DOPA is a key compound in the formation of marine adhesive proteins, such as those found in mussels. It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. L-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible substrate.

References

"L-dopa for RLS". Bandolier. 1 April 2007. Retrieved 2008-10-16.
http://students.cis.uab.edu/porce/page4.html
Hyland K, Clayton PT (1992). "Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology" (PDF). Clinical chemistry. 38 (12): 2405–10. PMID 1281049. {{cite journal}}: Unknown parameter |month= ignored (help)
Merims D, Giladi N (2008). "Dopamine dysregulation syndrome, addiction and behavioral changes in Parkinson's disease". Parkinsonism Relat Disord. 14 (4): 273–280. doi:10.1016/j.parkreldis.2007.09.007. PMID 17988927.
Cheng N, Maeda T, Kume T; et al. (1996). "Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons". Brain research. 743 (1–2): 278–83. doi:10.1016/S0006-8993(96)01056-6. PMID 9017256. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Basma AN, Morris EJ, Nicklas WJ, Geller HM (1995). "L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation". Journal of neurochemistry. 64 (2): 825–32. doi:10.1046/j.1471-4159.1995.64020825.x. PMID 7830076. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Pardo B, Mena MA, Casarejos MJ, Paíno CL, De Yébenes JG (1995). "Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants". Brain research. 682 (1–2): 133–43. doi:10.1016/0006-8993(95)00341-M. PMID 7552304. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Mytilineou C, Han SK, Cohen G (1993). "Toxic and protective effects of L-dopa on mesencephalic cell cultures". Journal of neurochemistry. 61 (4): 1470–8. doi:10.1111/j.1471-4159.1993.tb13642.x. PMID 8376999. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Simuni T, Stern MB (1999). "Does levodopa accelerate Parkinson's disease?". Drugs & aging. 14 (6): 399–408. doi:10.2165/00002512-199914060-00001. PMID 10408739. {{cite journal}}: Unknown parameter |month= ignored (help)
Cotzias, GC; Papavasiliou, PS; Gellene, R (1969). "L-dopa in parkinson's syndrome". The New England journal of medicine. 281 (5): 272. doi:10.1056/NEJM196907312810518. PMID 5791298. {{cite journal}}: Cite has empty unknown parameter: |author-name-separator= (help); Unknown parameter |author-separator= ignored (help)

Waite, J. Herbert; et al. (2005). "Mussel Adhesion: Finding the Tricks Worth Mimicking". J Adhesion. 81: 1–21. doi:10.1080/00218460590944602. {{cite journal}}: Explicit use of et al. in: |author= (help)
Messersmith, Phillip B.; et al. (2006). "Rapid Gel Formation and Adhesion in Photocurable and Biodegradable Block Copolymers with High DOPA Content". Macromolecules. 39: 1740–1748. doi:10.1021/ma0518959. {{cite journal}}: Explicit use of et al. in: |author= (help)

External links

Study Reveals Details Of Mussels' Tenacious Bonds

v t e Stimulants
Adamantanes	Adapromine Amantadine Bromantane Memantine Rimantadine
Adenosine antagonists	8-Chlorotheophylline 8-Cyclopentyltheophylline 8-Phenyltheophylline Aminophylline Caffeine CGS-15943 Dimethazan Istradefylline Paraxanthine SCH-58261 Theobromine Theophylline
Alkylamines	Cyclopentamine Cypenamine Cyprodenate Heptaminol Isometheptene Methylhexaneamine Octodrine Propylhexedrine Tuaminoheptane
Ampakines	CX-516 CX-546 CX-614 CX-691 CX-717 IDRA-21 LY-404,187 LY-503,430 Nooglutyl Org 26576 PEPA S-18986 Sunifiram Unifiram
Arylcyclohexylamines	Benocyclidine Dieticyclidine Esketamine Eticyclidine Gacyclidine Ketamine Phencyclamine Phencyclidine Rolicyclidine Tenocyclidine Tiletamine
Benzazepines	6-Br-APB SKF-77434 SKF-81297 SKF-82958
Cathinones	3-FMC 3-MMC 3,4-DMMC 4-BMC 4-CMC 4-Methylbuphedrone 4-Methylcathinone 4-MEAP 4-Methylpentedrone Amfepramone Benzedrone Buphedrone Bupropion Butylone Cathinone Dimethylcathinone Ethcathinone Ethylone Flephedrone Hexedrone Isoethcathinone Mephedrone Methcathinone Methedrone Methylenedioxycathinone Methylone Mexedrone N-Ethylbuphedrone N-Ethylhexedrone Pentedrone Pentylone Phthalimidopropiophenone
Cholinergics	A-84,543 A-366,833 ABT-202 ABT-418 AR-R17779 Altinicline Anabasine Arecoline Bradanicline Cotinine Cytisine Dianicline Epibatidine Epiboxidine GTS-21 Ispronicline Nicotine PHA-543,613 PNU-120,596 PNU-282,987 Pozanicline Rivanicline Sazetidine A SIB-1553A SSR-180,711 TC-1698 TC-1827 TC-2216 Tebanicline UB-165 Varenicline WAY-317,538
Convulsants	Anatoxin-a Bicuculline DMCM Flurothyl Gabazine Pentetrazol Picrotoxin Strychnine Thujone
Eugeroics	Adrafinil Armodafinil CRL-40,940 CRL-40,941 Fluorenol Modafinil
Oxazolines	4-Methylaminorex Aminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
Phenethylamines	1-(4-Methylphenyl)-2-aminobutane 1-Methylamino-1-(3,4-methylenedioxyphenyl)propane 2-Fluoroamphetamine 2-Fluoromethamphetamine 2-OH-PEA 2-Phenyl-3-aminobutane 2,3-MDA 3-Fluoroamphetamine 3-Fluoroethamphetamine 3-Methoxyamphetamine 3-Methylamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-MA 4-MMA 4-MTA 6-FNE AL-1095 Alfetamine a-Ethylphenethylamine Amfecloral Amfepentorex Amidephrine 2-Amino-1,2-dihydronaphthalene 2-Aminoindane 5-(2-Aminopropyl)indole 2-Aminotetralin Acridorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Arbutamine β-Methylphenethylamine β-Phenylmethamphetamine Benfluorex Benzphetamine BDB BOH 3-Benzhydrylmorpholine BPAP Camfetamine Cathine Chlorphentermine Cilobamine Cinnamedrine Clenbuterol Clobenzorex Cloforex Clortermine Cypenamine D-Deprenyl Denopamine Dimethoxyamphetamine Dimethylamphetamine Dobutamine DOPA (Dextrodopa, Levodopa) Dopamine Dopexamine Droxidopa EBDB Ephedrine Epinephrine Epinine Etafedrine Ethylnorepinephrine Etilamfetamine Etilefrine Famprofazone Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Feprosidnine Fludorex Formetorex Furfenorex Gepefrine Hexapradol HMMA Hordenine 4-Hydroxyamphetamine 5-Iodo-2-aminoindane Ibopamine Indanylamphetamine Iofetamine Isoetarine Isoprenaline L-Deprenyl (Selegiline) Lefetamine Lisdexamfetamine Lophophine MBDB MDA (tenamfetamine) MDBU MDEA MDMA (midomafetamine) MDMPEA MDOH MDPR MDPEA Mefenorex Mephentermine Metanephrine Metaraminol Mesocarb Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxamine Methoxyphenamine MMA Methoxyphenamine MMDA MMDMA MMMA Morforex N,alpha-Diethylphenylethylamine N,N-Dimethylphenethylamine Naphthylamphetamine Nisoxetine Norepinephrine Norfenefrine Norfenfluramine Normetanephrine L-Norpseudoephedrine Octopamine Orciprenaline Ortetamine Oxifentorex Oxilofrine PBA PCA PCMA PHA Pentorex Phenatine Phenpromethamine Phentermine Phenylalanine Phenylephrine Phenylpropanolamine Pholedrine PIA PMA PMEA PMMA PPAP Prenylamine Propylamphetamine Pseudoephedrine Ropinirole Salbutamol (Levosalbutamol) Sibutramine Solriamfetol Synephrine Theodrenaline Tiflorex Tranylcypromine Tyramine Tyrosine Xylopropamine Zylofuramine
Phenylmorpholines	3-Fluorophenmetrazine Fenbutrazate Fenmetramide G-130 Manifaxine Morazone Morforex Oxaflozane PD-128,907 Phendimetrazine Phenmetrazine 2-Phenyl-3,6-dimethylmorpholine Pseudophenmetrazine Radafaxine
Piperazines	2C-B-BZP 3C-PEP BZP CM156 DBL-583 GBR-12783 GBR-12935 GBR-13069 GBR-13098 GBR-13119 JJC8-088 MeOPP MBZP oMPP Vanoxerine
Piperidines	1-Benzyl-4-(2-(diphenylmethoxy)ethyl)piperidine 2-Benzylpiperidine 2-Methyl-3-phenylpiperidine 3,4-Dichloromethylphenidate 4-Benzylpiperidine 4-Fluoromethylphenidate 4-Methylmethylphenidate Desoxypipradrol Difemetorex Diphenylpyraline Ethylnaphthidate Ethylphenidate Methylnaphthidate Isopropylphenidate JZ-IV-10 Methylphenidate (Dexmethylphenidate) Nocaine Phacetoperane Pipradrol Propylphenidate Serdexmethylphenidate SCH-5472
Pyrrolidines	2-Diphenylmethylpyrrolidine 4-Cl-PVP 5-DBFPV α-PPP α-PBP α-PCYP α-PHiP α-PHP α-PHPP α-PVP α-PVT Diphenylprolinol DMPVP FPOP FPVP MDPPP MDPBP MPBP MPHP MPPP MOPVP MOPPP Indapyrophenidone MDPV Naphyrone PEP Picilorex Prolintane Pyrovalerone
Racetams	Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide
Tropanes	4-fluorotropacocaine 4'-Fluorococaine Altropane (IACFT) Brasofensine CFT (WIN 35,428) β-CIT (RTI-55) Cocaethylene Cocaine Dichloropane (RTI-111) Difluoropine FE-β-CPPIT FP-β-CPPIT Ioflupane (I) Norcocaine PIT PTT RTI-31 RTI-32 RTI-51 RTI-112 RTI-113 RTI-120 RTI-121 (IPCIT) RTI-126 RTI-150 RTI-177 RTI-229 RTI-336 RTI-354 RTI-371 RTI-386 Salicylmethylecgonine Tesofensine Troparil (β-CPT, WIN 35,065-2) Tropoxane WF-23 WF-33
Tryptamines	4-HO-αMT 4-Methyl-αET 4-Methyl-αMT 5-Chloro-αMT 5-Fluoro-αMT 5-MeO-αET 5-MeO-αMT 5-MeO-DIPT 6-Fluoro-αMT 7-Methyl-αET αET αMT
Others	2-MDP 3,3-Diphenylcyclobutanamine Amfonelic acid Amineptine Amiphenazole Atipamezole Atomoxetine Bemegride Benzydamine BTQ BTS 74,398 Centanafadine Ciclazindol Clofenciclan Cropropamide Crotetamide D-161 Desipramine Diclofensine Dimethocaine Efaroxan Etamivan Fenisorex Fenpentadiol Gamfexine Gilutensin GSK1360707F GYKI-52895 Hexacyclonate Idazoxan Indanorex Indatraline JNJ-7925476 Lazabemide Leptacline Lomevactone LR-5182 Mazindol Meclofenoxate Medifoxamine Mefexamide Methamnetamine Methastyridone Methiopropamine Naphthylaminopropane Nefopam Nikethamide Nomifensine O-2172 Oxaprotiline PNU-99,194 PRC200-SS Rasagiline Rauwolscine Rubidium chloride Setazindol Tametraline Tandamine Thiopropamine Thiothinone Trazium UH-232 Yohimbine
ATC code: N06B

Antiparkinson agents (N04)

Dopaminergics

DA precursors	Levodopa (+benserazide, +carbidopa, +carbidopa/entacapone) Foslevodopa (+foscarbodipa) Melevodopa (+carbidopa)
DA receptor agonists	Ergoline: Bromocriptine Cabergoline Dihydroergocryptine Lisuride Pergolide Non-ergoline: Apomorphine Piribedil Pramipexole Ropinirole Rotigotine Talipexole
MAO-B inhibitors	Rasagiline Safinamide Selegiline
COMT inhibitors	Entacapone Opicapone Tolcapone
AAAD inhibitors	Benserazide (+levodopa) Carbidopa (+carbidopa, +melevodopa, +carbidopa/entacapone) Foscarbidopa (+foslevodopa)

Anticholinergics

Others

Adamantanes (e.g., amantadine, memantine, rimantadine)
Adenosine receptor antagonists (e.g., caffeine, istradefylline)
Budipine

WHO-EM
Withdrawn from market
Clinical trials:
- Phase III
- Never to phase III

v t e Dietary supplements
Types	Bodybuilding supplement Energy drink Energy bar Fatty acids Herbal supplements Minerals Prebiotics Probiotics (Lactobacillus Bifidobacterium) Protein supplements Vitamins
Vitamins and chemical elements ("minerals")	Retinol (Vitamin A) B vitamins Thiamine (B₁) Riboflavin (B₂) Niacin (B₃) Pantothenic acid (B₅) Pyridoxine (B₆) Biotin (B₇) Folic acid (B₉) Cyanocobalamin (B₁₂) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc
Other common ingredients	AAKG β-hydroxy β-methylbutyrate Carnitine Chondroitin sulfate Cod liver oil Copper gluconate Creatine Dietary fiber Echinacea Ephedra Fish oil Folic acid Ginseng Glucosamine Glutamine Grape seed extract Guarana Iron supplements Japanese honeysuckle Krill oil Lingzhi Linseed oil Lipoic acid Milk thistle Melatonin Red yeast rice Royal jelly Saw palmetto Spirulina St John's wort Taurine Wheatgrass Wolfberry Yohimbine Zinc gluconate
Related articles	Codex Alimentarius Enzyte Hadacol Herbal tea Nutraceutical Multivitamin Nutrition

Encoded (proteinogenic) amino acids

General topics

By properties

Aliphatic	Branched-chain amino acids (Valine Isoleucine Leucine) Methionine Alanine Proline Glycine
Aromatic	Histidine Tyrosine Tryptophan Phenylalanine
Polar, uncharged	Asparagine Glutamine Serine Threonine
Positive charge (pK_a)	Lysine (≈10.8) Arginine (≈12.5) Histidine (≈6.1) Pyrrolysine
Negative charge (pK_a)	Aspartic acid (≈3.9) Glutamic acid (≈4.1) Selenocysteine (≈5.4) Cysteine (≈8.3) Tyrosine (≈10.1)

Amino acids types: Encoded (proteins)
Essential
Non-proteinogenic
Ketogenic
Glucogenic
Secondary amino
Imino acids
D-amino acids
Dehydroamino acids

Metabolism: Protein metabolism, synthesis and catabolism enzymes

Essential amino acids are in Capitals

K→acetyl-CoA

LYSINE→	Saccharopine dehydrogenase Glutaryl-CoA dehydrogenase
LEUCINE→	3-Hydroxybutyryl-CoA dehydrogenase Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase HMG-CoA lyase HMG-CoA reductase Isovaleryl coenzyme A dehydrogenase α-Ketoisocaproate dioxygenase Leucine 2,3-aminomutase Methylcrotonyl-CoA carboxylase Methylglutaconyl-CoA hydratase (See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase)
TRYPTOPHAN→	Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase Arylformamidase Kynureninase 3-hydroxyanthranilate oxidase Aminocarboxymuconate-semialdehyde decarboxylase Aminomuconate-semialdehyde dehydrogenase
PHENYLALANINE→tyrosine→	(see below)

G→pyruvate
→citrate

glycine→serine→	Serine hydroxymethyltransferase Serine dehydratase glycine→creatine: Guanidinoacetate N-methyltransferase Creatine kinase
alanine→	Alanine transaminase
cysteine→	D-cysteine desulfhydrase
threonine→	L-threonine dehydrogenase

G→glutamate→
α-ketoglutarate

HISTIDINE→	Histidine ammonia-lyase Urocanate hydratase Formiminotransferase cyclodeaminase
proline→	Proline oxidase Pyrroline-5-carboxylate reductase 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 PYCR1
arginine→	Ornithine aminotransferase Ornithine decarboxylase Agmatinase
→alpha-ketoglutarate→TCA	Glutamate dehydrogenase
Other	cysteine+glutamate→glutathione: Gamma-glutamylcysteine synthetase Glutathione synthetase Gamma-glutamyl transpeptidase glutamate→glutamine: Glutamine synthetase Glutaminase

G→propionyl-CoA→
succinyl-CoA

VALINE→	Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex Enoyl-CoA hydratase 3-hydroxyisobutyryl-CoA hydrolase 3-hydroxyisobutyrate dehydrogenase Methylmalonate semialdehyde dehydrogenase
ISOLEUCINE→	Branched-chain amino acid aminotransferase Branched-chain alpha-keto acid dehydrogenase complex 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
METHIONINE→	generation of homocysteine: Methionine adenosyltransferase Adenosylhomocysteinase regeneration of methionine: Methionine synthase/Homocysteine methyltransferase Betaine-homocysteine methyltransferase conversion to cysteine: Cystathionine beta synthase Cystathionine gamma-lyase
THREONINE→	Threonine aldolase
→succinyl-CoA→TCA	Propionyl-CoA carboxylase Methylmalonyl CoA epimerase Methylmalonyl-CoA mutase

G→fumarate

PHENYLALANINE→tyrosine→

tyrosine→melanin: Tyrosinase

G→oxaloacetate

asparagine→aspartate→	Asparaginase/Asparagine synthetase Aspartate transaminase

Neurotransmitter metabolic intermediates

Catecholamines

Anabolism

Phenylalanine → Tyrosine → DOPA (levodopa) → Dopamine → Norepinephrine → Epinephrine

Catabolism

Dopamine	3,4-Dihydroxyphenylacetaldehyde (DOPAL) 3,4-Dihydroxyphenylacetic acid (DOPAC) Homovanillyl alcohol Hydroxytyrosol (3,4-dihydroxyphenylethanol; DOPET) 3-Methoxytyramine (3-MT) Homovanillic acid (HVA)
Norepinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) 3,4-Dihydroxymandelic acid (DHMA) Normetanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL) Vanillylmandelic acid (VMA) 3,4-Dihydroxyphenylethylene glycol (DOPEG, DHPG) 3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG)
Epinephrine	3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL, DHMAL) Metanephrine 3-Methoxy-4-hydroxymandelaldehyde (MHMAL)

Tryptophan→Serotonin

Anabolism	Tryptophan 5-Hydroxytryptophan (5-HTP)
Catabolism	5-Hydroxyindoleacetaldehyde (5-HIAL) 5-Hydroxyindoleacetic acid (5-HIAA) 5-Hydroxytryptophol (5-HTOL)