Biochem 48 Metabolism Of The Nervous System

Front 1

ependymal cells

Back 1

line cavities of the brain and spinal cord

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catecholamine neurotransmitters and what are they derived from

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dopamine, norepi, and epi; derived from L-tyrosine

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what is serotonin synthesized from

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tryptophan

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what is acetylcholine derived from

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choline, supplied from diet or synthesized and stored as part of phosphatidylcholine

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what are glutamate and GABA derived from

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alpha-ketoglutarate in the TCA cycle

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what is glycine derived from

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serine in brain

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ischemia causes what in brain

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increased calcium, swelling, glutamate excitotoxicity, and NO generation

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disorder of peroxisomal fxn

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Refsum disease=interference in very long chain fatty acid oxidation and alpha-oxidation

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lysosomal disease

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mucopolysaccharidoses-inability to degrade complex lipids and glycolipids

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astrocyte fxns

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phagocytizing debris left behind by cells, providing lactate (from glucose metabolism) as carbon source for neurons, and controlling brain extracellular ionic environment (regulate ECF)

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glucose transport in brain

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GLUT-1 transporter across endothelial membranes and GLUT-3 on neurons

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at what level do ppl begin feeling hypoglycemic symptoms

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~60 mg/dL

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what other monocarboxylic acids are transported into the brain

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L-lactate, acetate, pyruvate, and ketone bodies (acetoacetate and B-hydroxybutyrate)

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treatment of ppl with GLUT1 deficiency syndrome

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high fat, low car diet to force ketone body formation

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what causes mental retardation (at least in part) in PKU and maple syrup urine diseaes

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high levels of either phenylalanine or branch-chained aas; results in competative inhibition of other large, neutral aas

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what are the large, neutral aas (LNAAs)

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phenylalanine, leucine, tyrosine, isoleucine, valine, tryptophan, methionine, and histidine

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how does insulin, transferrin, and ILGF cross blood-brain barrier

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receptor-mediated transcytosis

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major small N-containing molecule neurotransmitters

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glutamate, GABA, glycine, acetylcholine, dopamine, norepi, serotonin, and histamine (also aspartate, epi, and NO)

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neuropeptides

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endorphins, GH, TSH

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reserpine

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blocks catecholamine uptake into vesicles

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where does tyrosine come from

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diet of synthesized in liver from phenylalanine

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first and rate limiting steps of catecholamine synthesis from tyrosine

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hydroxylation of tyrosine ring by tyrosine hydroxylase

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where is the enzyme required to form norpei from dopamine located

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within storage vesicles

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epinephrine synthesis required adequate B12 and folate due to

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use of SAM

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what transports catecholamines into vesicles

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protein VMAT2 (vesicle monoamine transporter 2); driven by H+ gradient across membrane

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MAO-A

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preferentially deaminates norepi and serotonin

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MOA-B

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wide spectrum of phenylethylamines

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indicator of dopamine degradation

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cerebrospinal homovanillylmandelic acid (HVA); decreased in Parkinson's

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tyramine

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degradation product of tyrosine that can cause headaches, palpitations, nausea, and vomiting, and elevated BP in large quantities; mimics norepi; inactivated by MAO-A

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phenoxybenzamine

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a1 and a2 adrenergic receptor antagonist

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what foods contain tyramine

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cheese, wine; processed over long periods

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histaminergic neurons are found

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in tuberomammilary nucleus of posterior basal hypothalamus; project to nearly all areas of CNS

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histamine is derived from

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histidine in single enzymatic step

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histamine effects in allergic response

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vasodilation and increase permeability of blood vessel walls

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histamine in brain

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excitatory neurotransmitter; hence antihistamines have SE of drowsiness

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formation of SAM via recycling of homocysteine requires

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tetrahydrofolate and vit B12

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Tiagabine

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inhibits reuptake of GABA from the synapse; treat epilepsy and other convulsant disorders

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synthesis of glutamate in neurons

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generally synthesized de novo tather than taken up from blood; TCA cycle derived from a-ketoglutarate

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GABA synthesis

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decarboxylation of glutamate in single step

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GABA shunt

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uptake of GABA in glial cells which convert to glutamine and then transport to neurons which convert back to glutamate

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aspartate synthesis

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excitatory; TCA cycle from oxaloacetate via transamination; can't pass through blood-brain barrier

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glycine synthesis

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major inhibitory of spinal cord; de novo within nerve terminal from serine; requires folic acid

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NO is synthesized from

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arginine via NO synthase

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what does NO activate in target cells

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soluble guanylate cyclase increasing cGMP

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cGMP in smooth muscle

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activates one or more protein kinases causing relaxation and dilation

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possible retrograde messengers in CNS

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NO, arachidonic acid, CO

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symptoms of hypoglycemia from 45 to 36 mg/dL are mostly due to

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decrease neurotransmitter synthesis

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hypoglycemia below 1 mM (18 mg/dL)

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high energy P levels depleted, EEG become isoelectric, and neuronal cell death ensues

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what brain areas are particularly sensitive to hypoglycemia

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hippocampal and cortical structures

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glutamate excitotoxicity in hypoglycemia

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failure of energy-dependent reuptake pumps-leads to prolonged opening of receptor ion channel and influx of lethal amounts of Ca2+

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effect of oxaloacetate use to make glutamate

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must be replaced in order for oxidation of acetyl CoA to continue-2 pathways

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what esential fatty acids enter the brain

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linoleic and linolenic acid; all others synthesized

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oligodendrocyte myelin synthesis per day

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4 times its own weight

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Two proteins in CNS that constitute 60-80% of total

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proteolipid protein (PLP) and myelin basic proteins (MBPs)

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PLP

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hydrophobic and forms large aggregates in aqueous soln and relatively resistant to proteolysis; highly conserved; promote formation and stabilization of multilayered myelin structure

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MBPs

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extracted from membrane and soluble in aqueous soln; located on cytoplasmic face of myelin membranes