Biochem 48 Metabolism Of The Nervous System

Front 1

what cells form the support matrix for neurons in the CNS?

Back 1

oligodendrocytes, astrocytes

Front 2

what is the result of damage to oligodendrocytes?

Back 2

apoptosis without regeneration leading to demyelination

Front 3

which cells myelinate CNS neurons?

Back 3

oligodendrocytes

Front 4

ratio of oligodendrocytes to neurons compared to that of Schwann cells to neurons?

Back 4

1 oligodendrocyte to many neurons

1 Schwann cell to 1 neuron

Front 5

primary differences between oligodendrocytes and Schwann cells?

Back 5

oligodendrocytes = CNS, Schwann cells = PNS

Schwann cells help regenerate neuron if damaged, oligodendrocytes do not

Front 6

which cells in the CNS phagocytose debris left behind by cells, provide lactate (from glucose metabolism), control the brain extracellular ionic environment and regulate the content of the ECF?

Back 6

astrocytes

Front 7

types of glial cells?

Back 7

astrocytes, oligodendrocytes, Schwann cells

Front 8

immunologically responsive cells in the CNS?

Back 8

microglial cells

Front 9

from where are neural stem cells generated?

Back 9

ependymal layer

Front 10

in what ways do the endothelial cells of the BBB act as an active barrier?

Back 10

contain enzyme systems that can metabolize NTs and toxic chemicals, actively pump hydrophobic molecules (esp xenobiotics) that get into endothelial cells back into the blood, and actively transport needed molecules through

Front 11

how does glucose in the systemic blood get to neurons?

Back 11

transported through endothelial membranes by GLUT-1 transporter, then transported into neuron by GLUT-3

Front 12

seizures, developmental delay, complex motor disorder, CSF glucose-to-blood glucose < 0.4

Back 12

GLUT1 deficiency syndrome

Front 13

treatment for GLUT1 deficiency syndrome?

Back 13

ketogenic (high-fat, low-carb) diet

Front 14

which amino acids are transported into the CSF and how?

Back 14

large neutral amino acids (Phe, Leu, Tyr, Iso, Val, Trp, Met, His) enter via a single amino acid transporter

Front 15

what is the cause of the mental retardation from PKU and MSUD?

Back 15

the single LNAA transporter gets overwhelmed by the high levels of Phe or BCAAs in the blood

Front 16

what are the small nitrogen-containing NTs?

Back 16

Glutamate, GABA, glycine, ACh, DA, NE, 5HT, histamine, Epi, aspartate, nitric oxide

Front 17

drug that blocks catecholamine uptake into vesicles, used as antihypertensive and antiepileptic

Back 17

Reserpine

Front 18

NT's synthesized from L-tyrosine?

where does tyrosine come from?

Back 18

DA, NE, Epi

diet or made in liver from Phe by phenylalanine hydroxylase

Front 19

rate limiting step of catecholamine synthesis?

Back 19

hydroxylation of tyrosine to DOPA (dihydroxyphenylalanine) by tyrosine hydroxylase

Front 20

how is NE made?

Back 20

in NE-secreting neurons, DA is hydroxylated by dopamine beta hydroxylase to NE (requires copper and vitamin C)

Front 21

what cofactors are required to convert NE to Epi?

Back 21

vitamin B12 and folate

Front 22

acidic proteins that complex with the NT and ATP in the vesicle; elevated levels of them in the blood in neuroendocrine tumors?

Back 22

chromogranins

Front 23

two major enzymes responsible for the major processes of catecholamine degradation?

Back 23

COMT, MAO

Front 24

locations where MAOs are found and function of each?

Back 24

outer mitochondrial membrane of many cells; breaks down catecholamines

liver and other sites; protects against ingestion of dietary biogenic amines such as tyramine (wine, cheese)

Front 25

CSF indicator of DA degradation?

Back 25

HVMA (HVA, homovanillylmandelic acid)

Front 26

albinism is caused by what defective enzymes?

Back 26

copper-dependent tyrosine hydroxylase of melanocytes that convert tyrosine to melanin

Front 27

degradation product of tyrosine that, in large quantities, causes HA, palpitations, N/V, and HTN?

what inactivates it?

Back 27

tyramine
(NE receptor agonist)

MAO-A
(hence, avoid tyramines if on MAO-I)

Front 28

what inhibits tyrosine hydroxylase, the rate limiting enzyme of catecholamine synthesis?

Back 28

free cytosolic catecholamines
(tyr hydroxylase activated by depolarization of nerve terminal

Front 29

drug that blocks α1 and α2 adrenergic receptors?

Back 29

phenoxybenzamine

Front 30

what NTs are inactivated by MAO?

Back 30

catecholamines and serotonin

Front 31

selective irreversible inhibitor of MAO-B used to treat Parkinson's dz, but has no antidepressant effects?

Back 31

Deprenyl

Front 32

selective irreversible inhibitor of MAO-A used as an antidepressant but suffers from the "cheese" effect?

Back 32

clorgyline

Front 33

3rd gen, specific, reversible MAO-A inhibitor that does not suffer from the "cheese" effect?

Back 33

Moclobemide

Front 34

NTs synthesized from tryptophan?

Back 34

serotonin, melatonin

Front 35

what enzymes in NT synthesis pathways require tetrahydrobiopterin (BH4)?

Back 35

Phe hydroxylase (Phe --> Tyr)
Tyr hydroxylase (Tyr --> dopa)
Trp hydroxylase (Trp --> 5HT)

Front 36

how is histamine synthesized?

Back 36

Histidine + His decarboxylase + pyridoxal phosphate = histamine

Front 37

low levels of this NT cause increased appetite, or depression, or both

Back 37

serotonin

Front 38

drug developed as an appetite suppressant and paired with an epinephrine agonist to counteract sleepiness d/t presence of optical isomer?

Back 38

fenfluramine + phentermine

Front 39

why do antihistamines make you sleepy?

Back 39

in peripheral tissues, blocks histamine vasodilation and capillary permeability effects, but in brain, blocks stimulatory effect of histamine as a NT

Front 40

the halting of what biochemical process is the primary cause for the neurologic sxs of vitamin B12 deficiency?

Back 40

choline synthesis

(methyl groups for choline synth donated by SAM, which is chgd to S-adenosyl-Hcy. Recycling of Hcy to regenerate SAM requires tetrahydrofolate and B12)

Front 41

where do the building blocks for ACh synthesis come from?

Back 41

Acetyl CoA - from pyruvate decarboxylation in TCA cycle

Choline - from diet and from hydrolysis of phosphatidylcholine and sphingomyelin in membrane lipids

Front 42

tx used in patients suffering from tardive dyskinesia?

Back 42

supplementation of diet with lecithin (phophatidylcholine) to increase brain ACh

Front 43

why is extra folate and B12 needed during gestation?

Back 43

choline synthesis is dependent on them - fetus has high demand for choline in brain development and myelination

Front 44

_______deficiency , ______ deficiency, or _____ deprives the brain of Acetyl CoA for ACh synthesis and for ATP generation from TCA cycle?

Back 44

inherited pyruvate dehydrogenase deficiency, thiamine deficiency, or hypoxia

Front 45

NT synthesized from TCA cycle intermediate α-ketoglutarate?

what other way can it be formed?

Back 45

Glutamate

can also be synthesized from glutamine using glutaminase

Front 46

NT synthesized by the decarboxylation of glutamate?

Back 46

GABA

Front 47

drug that inhibits reuptake of GABA from the synapse, used in treating epilepsy and other convulsant disorders?

Back 47

Tiagabine

Front 48

excitatory NT synthesized from TCA intermediate oxaloacetate, only found in PNS?

Back 48

Aspartate

Front 49

how is the major inhibitory NT in the spinal cord synthesized?

Back 49

(glycine) made from serine + serine hydroxymethyltransferase + folic acid in the nerve terminal

Front 50

how is NO synthesized?

Back 50

arginine + NO synthase

Front 51

how many ATP/glucose are generated in anaerobic glycolysis vs. complete aerobic oxidation to CO2?

Back 51

2 ATP/glucose vs. 32 ATP/glucose

Front 52

what is the main cause of the cognitive dysfxn seen in mild hypoglycemia or mild hypoxia?

Back 52

decreased NT synthesis

Front 53

why does hypoxia decrease amounts of ACh, glutamate, GABA, and catecholamines?

Back 53

ACh: pyruvate dehydrogenase requires O2

Glu: precursor comes from TCA cycle, and GABA comes from Glu

Catecholamines: hydroxylases require O2

Front 54

disorder of peroxisome biogenesis leading to deficient peroxisome breakdown of BCFAs and VLCFAs leading to neurologic damage, cerebellar degeneration, and peripheral neuropathy?

Back 54

Refsum disease

Front 55

what is the main myelin lipid and what advantage does it have over the lipid of other cell membranes?

Back 55

galactosylcerebroside

pack more tightly than phosphatidylcholine

Front 56

what proteins maintain myelin structure in CNS and PNS?

Back 56

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

PNS: Po

Front 57

pharmacologic tx for inoperable pheochromocytoma?

Back 57

long-acting α1 and α2-adrenergic blocker (phenoxybenzamine)
+
β1 and β2-adrenergic blocker (propanolol)