| A | B |
|---|
| MAO | inactivates catecholamines that are not protected in a vesicle |
| catechol-O-methyl transferase (COMT) | indirectly dependent on vitamin B-12 and folate |
| COMT | transfers SAM -CH3 to catecholamine |
| tyrosine hydroxylase | rate limiting enzyme in catecholamine biosynthesis |
| catecholamines compete at binding site for pterin cofactor | inhibition of tyrosine hydroxylase |
| activates tyrosine hydroxylase | depolarization of the nerve terminal |
| phosphorylation of tyrosine kinase | result in tight enzyme-BH4 binding; less sensitivity to inhibition |
| result of prolonged sympathetic neuronal activity | incr. mRNA for tyrosine kinase and DBH in perikarya |
| CREB | cAMP response element binding protein |
| tyramine | stimulates NErcptrs; headaches, palpitations, nausea/vomiting |
| degradation pdt of tyrosine, inactivated by MAO | tyramine |
| chromogranins | elevated levels may appear in patients with neuroendocrine tumors |
| occurs in cytosol | converstion of tyrosine > L-dopa > dopamine |
| B-hydroxylation of dopamine > NE | occurs in vesicles |
| synthesis depnds on adequate levels of B12 and folate | epinephrine |
| major site of epinephrine synthesis | adrenal medulla |
| dopamine beta hydroxylase (DBH) | requires Vitamine C as electron donor |
| first step in catecholamine synthesis | hydroxylation of tyrosine rine |
| phenyl ring with two adjacent -OH groups | catechol |
| second step in catecholamine synthesis | decarboxylation of dopa to form dopamine |
| dopa decarboxylase, histidine decarboxylase | require pyridoxyl phosphate (PLP) |
| L-preferring amino acid transporter | allows large amino acids to rapidly enter the CSF |
| synthesized in the brain | GABA, alanine, glycine, proline |
| cross blood/brain/barrier via receptor mediated endocytosis | insulin, transferrin |
| synthesized from tryptophan | serotonin, melatonin |
| requires BH4 to hydroxylate tryptophan ring | tryptophan hydroxylase |
| can be inactivated by MAO | serotonin |
| synthesized in the pineal gland in response to the light-dark cycle | melatonin |
| histaminergic neuronal cells are found in | tuberomammillary nucleus of posterior basal hypothalamus |
| mast cells in nervous system | thalamus, hypothalamus, dura mater, leptomeninges, choriod plexus |
| produced by mast cells and neuronal fibers | histamine |
| have high affinity uptake system for histamine | astrocytes |
| first step in inactivation of histamine | methylation |
| second step of inactivation of histamine | oxidation by MAO-B |
| diamine oxidase deaminates then oxidized to carboxylic acid | inactivation of histamine in peripheral tissues |
| synthesized in presynaptic terminal by ChAT | acetyl CoA + choline = acetylcholine |
| Choline is taken up in terminal by blood via | low affinity transport sytem ( high Km) |
| Choline is taken up from the synaptic cleft via | high affinity transport mechanism ( low Km) |
| Hydrolysis of membrane lipids is highly regulated because | Choline can be stored in phosphatidylcholine |
| acetyl group for ACh synthesis is derived from | pyruvate dehydrogenase reaction |
| Glucose oxidation is the major source for acetyl groups in neurons because | neurons have limited capacity to oxidize fatty acids to acetyl CoA |
| acetylcholinesterase reactive serine group | forms a covalent bond with acetyl group to inactivate ACh |
| rate limiting in ACh synthesis | supply of choline |
| excitatory neurotransmitter | glutamate |
| synthesized de novo from glucose within nerve terminals | glutamate does not readily cross the bbb |
| precursor for glutamate synthesis | TCA cycle intermediate, alpha-keto-glutarate |
| removal of glutamate from synaptic cleft | high affinity uptake systems in nerve terminals and glial cells |
| major inhibitory neurotransmitter of CNS | GABA |
| GAD glutamic acid decarboxylase | single step enzyme forms GABA from glutamate |
| serves as a transporters of glutamate between cells in CNS | glutamine |
| lack GAD, cannot synthesize GABA | glial cells |
| GABA shunt | produces glutamate in glial cells |
| vitamin B12 requirement for choline synthesis | contributes to the neuropathy associated with deficiency |
| aspartate | excitatory neurotransmitter synthesized from TCA cycle intermediate oxaloacetate |
| glycine | major inhibitory neurotransmitter of the spinal cord |
| synthesizeglycine from serine requires folic acid | serine hydroxymethyltransferase |
| retrograde messenger | NO influences neurotransmitter releases |
| stimulates guanyl cyclase to produce cGMP | NO causes smooth muscle relaxation |
| inhibition of pyruvate dehydrogenase | diminishes acetylcholine synthesis |
| glutamate and GABA synthesis | depend on functioning TCA cycle |
| elevated NADH levels | inhibit TCA cycle enzymes |
| NADH levels increase ( cannot be converted back to NAD+) | when oxygen is unavailable to accept electrons |
