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Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info
|
Home, Search, Index, Links, Pathology, Molecules, Syndromes, Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info |
| Enzyme or Protein | Biochemistry | Syndromes |
|
Phenylalanine hydroxylase (PAH) 
|
L-phenylalanine to L-tyrosine | Phenylketonuria
|
|
Tyrosine hydroxylase (TH)
|
L-tyrosine to L-DOPA |
Segawa syndrome
|
|
DOPA decarboxylase (DDC)
|
L-DOPA to dopamine; 5OH-tryptophan to serotonin |
Neonatal seizures; Hypotonia; Infantile death AADC deficiency |
|
Dopamine β-hydroxylase (DBH)
|
Dopamine to Norepinephrine | Orthostatic
|
|
Monoamine
|
Norepinephrine to dihydroxyphenylglycol With aldehyde reductase
|
Brunner syndrome
Retardation: Mild Impulsive behavior |
|
Monoamine
|
Norepinephrine to dihydroxyphenylglycol With aldehyde reductase
|
? asymptomatic
Linkage: Norrie syndrome |
|
Catechol-O- Methyltransferase (COMT)
|
Degradation of dopamine, epinephrine and norepinephrine |
Variant
Linkage Velo-cardio-facial
&DeGeorge syndrome |
|
Copper-transporting ATPase 1
|
ATP
to ADP Reduced DβH activity |
Menkes
Occipital horn SMAX3 |
|
GTP-cyclohydrolase 1 (GCH1)
|
Biopterin H4 synthesis: Step 1 GTP to D-erythro-7,8- dihydroneopterin (PO4)3 |
L-DOPA responsive dystonia Hyperphenylalaninemia: Severe
|
|
Quinoid Dihydropteridine Reductase (QDPR)
|
Biopterin H2 to |
Phenyketonuria: Atypical
|
|
Carbinolamine dehydratase (PCBD1)
|
4a-OH-Biopterin H4 to Biopterin H2 |
Phenyketonuria: Mild
|
|
Tyrosinase
|
Tyrosine to Dopaquinone | Albinism
|
|
Phenolsulfotransferase
|
Catecholamine inactivator by sulfoconjugation |
? |
|
Norepinephrine transporter (SLC6A2)
|
Removes NE from synaptic cleft |
Orthostatic Intolerance
|
|
Dopamine receptor D2
|
Neuroleptic receptor |
Polymorphism: ↓ Risk of Dopamine dystonia |
|
Dopamine |
Iodosulpride |
Essential tremor 1
Schizophrenia Mouse k/o: Hyperactivity |
|
Dopamine |
Clozapine: High affinity | Autonomic hyperactivity |
|
Dopamine |
. | ? |
|
Vesicular amine transporter 1
(SLC18A1)
|
Adrenal chromaffin granules | ? |
|
Vesicular amine transporter 2 (SLC18A2)
|
Accumulates cytosolic monoamines into Brain synaptic vesicles |
Site of action of Reserpine & Tetrabenazine Parkinsonism-dystonia, infantile, 2
|
|
Aldehyde dehydrogenase A1 (ALDHA1)
|
Dopamine inactivation with MAO |
? |
|
Neurofibromin
|
Tumor suppressor | Pheochromocytoma
Neurofibromatosis
|
|
G7 protein
|
Tumor suppressor | Pheochromocytoma
Von Hippel-Lindau
|
|
RET tyrosine-protein kinase receptor
|
Oncogene
|
Pheochromocytoma
Multiple endocrine neoplasia 2
|
| Transmitter metabolism | |||
|---|---|---|---|
| Precursors: | Tyrosine ® (a) L-dihydroxyphenylalanine (L-DOPA) (b) dopamine | ||
| Synthesizing enzymes: |
(a) Tyrosine hydroxylase, (b) L-aromatic amino acid decarboxylase (DOPA decarboxylase) | ||
| Metabolizing enzymes: | MAO and COMT | ||
| Metabolites: | 3,4-Dihydroxyphenylacetic acid (DOPAC) Homovanillic acid (HVA) | ||
| Dopamine Receptors | ||||
|---|---|---|---|---|
| Receptor subtypes |
Agonists | Antagonists | Second messenger | Disorders |
| D1
|
SKF 38393 Dihydrexiedine |
Sch 23390 SKF83566 SCH39166 |
Positive: cAMP G-protein Stimulate adenylyl cyclase |
Mouse knockout Hyperactivity Diastolic hypertension |
| D2
|
(+)PHNO Bromocriptine |
(s)-Sulpiride Raclopride Domperidone Haloperidol |
Positive: gK+ G-protein Inhibit adenylyl cyclase |
Myoclonus-Dystonia
Anti-psychotic drugs |
| D3
|
7-OH-DPAT PD128907 BP897 |
Nafadotride | Positive: Ion channel | Mouse knockout Hyperactivity |
| D4
|
. | L745870 L741742 U101387 |
Positive: Ion channel | Autonomic dysfunction |
| D5
|
. | . | Positive: cAMP G-protein |
Focal dystonia Blepharospasm
|
| Transmitter Metabolism | |||
|---|---|---|---|
| Precursors: | L-Tyrosine (a) → L-DOPA (b) → Dopamine (c) → Noradrenaline (d) → Adrenaline | ||
| Synthesizing enzymes: | (a) Tyrosine hydroxylase, (b) L-aromatic amino acid decarboxylase, (c) Dopamine ß-hydroxylase, (d) Phenylethanolamine-N-methyl transferase | ||
| Metabolizing enzymes: | MAO and COMT | ||
| Metabolites: | Vanillylmandelic acid (VMA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) | ||
| Adrenoceptors | ||||
|---|---|---|---|---|
| Receptor subtypes | Transmitter | Agonists | Antagonists | Second messenger |
| α(1A)
α(1C) | NA > A | A61603 | KMD3213 (+)-niguldipine 5-methyluradipil |
Ca++: Influx into cell |
| α(1B)
|
NA = A | . | Spiroperone AH1111OA Chloroethylclonidine |
PI & Ca++; G-protein |
| α(1D)
|
NA = A | . | BMY7378 | PI & Ca++; G-protein |
| α(2A)
|
A > NA | Oxymetazoline | . | (-ve)cAMP, (down)gCa++, (down)gK+; G-protein |
| α(2B)
|
A > NA | . | Prazosin ARC 239 |
(-ve)cAMP, (down)gCa++; G-protein |
| α(2C)
|
A > NA | . | Prazosin ARC 239 |
(-ve)cAMP; G-protein |
| β(1)
|
NA > A | Xamoterol, RO363 |
Atenolol CGP20712A Betaxolol |
(+ve)cAMP; G-protein |
| β(2)
|
A > NA | Procaterol Zinterol |
ICI118551 | (+ve)cAMP; G-protein |
| β(3)
|
NA > A | BRL37344 | Bupranolol SR59230A |
(+ve)cAMP; G-protein |
NB: (+ve) indicates increase; (-ve) indicates decrease.
also has an absolute requirement for
tetrahydrobiopterin, for the oxidation of arginine to nitric oxide. Animals can synthesize tetrahydrobiopterin
in vivo from GTP through several enzymatic reactions. The conversion of GTP to
D-erythro-7,8-dihydroneopterin triphosphate is the first step in tetrahydrobiopterin biosynthesis,
and GTP cyclohydrolase I catalyzes this reaction. This step is thought to be
rate-limiting in the pathway.