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59 Cards in this Set
- Front
- Back
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Draw catechol
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Benzene ring with adjacent hydroxyl groups
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What type of neurotransmitter are dopamine, norepinephrine, and epinephrine? Where are they produced?
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Catecholamines:
Dopamine - dopaminergic neurons Norepinephrine - norepe neurons Epinephrine - adrenal medulla |
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What essential amino acid is required for synthesis of catecholamine?
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Phenylalanine
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What cofactor is required for hydroxylation of rings?
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Tetrahydrobiopterin (BH4)
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What cofactor is required for decarboxylase?
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Pyridoxal phosphate (PLP)
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What are the steps in producing the catecholamines?
What cofactor is needed for hydroxylation of a ring? What cofactor is required for decarboxylation? |
-Phenylalanine
-(ring hydroxylation) Tyrosine -(ring hydroxylation) Dopa -(decarboxylation) Dopamine -(hydroxylation) norepinephrine -(methyltransferase) Epinephrine -Tetrahydrabiopterin (BH4) -Pyridoxal phosphate (PLP) |
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What cofactor is required for the methylation of norepinephrine to epinephrine?
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SAM (S-adenosylmethionine)
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What step of the synthesis of catecholamines used a mixed function oxidase reaction to to hydroxylate the beta-carbon?
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From dopamine to norepinephrine. Cofactors are Cu2+ and Vit C
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What are the two key enzymes of deactivation of catecholamines?
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COMP (Catechol-O-methyltransferase) and MAO (Monoamine oxidase)
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What is the net reaction for COMT (catechol-O-methyltransferase)?
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SAM + ROH --> ROCH3 + SAH
(methyl group is transferred from S-adenosylmethionine to enzyme) |
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What is the net reaction for MAO (monoamine oxidase)?
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amine + O2 + H2O --> aldehyde + H2O2 + NH3
(The amine is converted to an aldohyde and will be reduced to alcohol or acid) |
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What is the cheese effect?
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If a person is taking an MAOi and consumes foods containing tyramine, they can have an acute attack of hypertension. This happens because tyramine mimics norepinephrine and stimulates their receptors.
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What step of seretonin synthesis includes a mixed function oxidase?
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The hydroxylation of the ring.
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What neurotransmitters are synthesized from phenylalanine?
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Dopamine, norepinephrine, epinephrine
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What neurotransmitter(s) are synthesized from tryptophan?
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Seretonin
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What inactivates norepinephrine?
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Both MAO and COMT
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What inactivates seretonin?
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MAO
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What neurotransmitter(s) are synthesized from histidine?
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Histamine
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How does histidine become histamine?
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Decarboxylation, requires pyridoxal phosphate.
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How is histamine inactivated?
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In peripheral tissues, diamine oxidase oxidizes histamine to an acetaldehyde.
In the brain, histamine is methylated (requires S-adenosylmethionine) and then MAO creates the aldehyde. |
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How is acetylcholine made?
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Acetyl CoA from glycolysis is the acctivated intermediate and combines with choline, either from the diet or from phosphotidylcholine.
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How is acetylcholine inactivated?
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Acetylcholinesterase breaks it down to acetic acid and choline.
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How is glutamate synthesized? (2 ways)
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Glutamate is formed from:
-glutamine -alpha-ketoglutarate (2 pathways) |
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How is GABA synthesizes?
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Glutamine is synthesized from glutarate. Glutamine is decarboxylated which requires pyridoxal phosphate (PLP) and this creates gamma aminobutyric acid.
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What is a normal carrier of nitrogen through the body?
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Glutamine
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How (and where) is GABA deactivated?
What is the normal carrier of N in the blood? |
gamma-Aminobutyric acid is deactived in the glial (supporting) cell by transamination. This creates:
GABA-->Succinate semi-aldehyde & alpha-ketoglutarate-->Glutamate -Glutamine |
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What are three functions of nitric oxide?
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-Signal macrophages to destroy a damaged cell
-Smooth muscle dilation -Neurotransmission |
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Where does nitric oxide come from?
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It is a sideproduct of arginine being converted to citrulline.
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How does nitric oxide act as a vasodilator?
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Nitric acid activates guanylate cyclase.
cGMP causes smooth muscle relaxation. |
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How does Viagra work?
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Viagra blocks the effect of phosphodiesterase. Phosphodiesterase inactivates cGMP but cGMP is a second messenger for smooth muscle relaxation. This increases blood flow to the penis and aids in erection.
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What type of blood cell:
Thrombycyte |
Platelet
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What type of blood cell:
Neutrophil |
WBC, granulocyte (PMN)
Major phagocytic cell in blood. Migrates to site of inflammmation |
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What type of blood cell:
Eosinophil |
WBC, granulocytes (PMN)
Phagocytic, parasite defense |
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What type of blood cell:
Basophil |
WBC, granulocyte (PMN)
Allergic reaction; releases histamine, heparin, leukotrienes. |
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What type of blood cell:
Lymphocyte |
WBC, mononuclear
B and T cells; acquired immunity. NK cells innate immunity. |
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What type of blood cell:
Monocyte |
WBC, mononuclear
Circulating precursors of tissue macrophages |
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What three things can a pluripotent stem cell become?
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-CFU-GEMM (all blood cells except lymphocytes and NK cells)
-Lymphoid stem cell (T and B lymphcytes) -NK precursor (NK cells) |
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Trace the differentiation of a RBC.
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-Pluripotent cell
-CFU-GEMM -BFU-EMeg -BFU-E -CFU-E -Normoblast -Reticuloyte -RBC |
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What is a normoblast?
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A premature RBC with nuclei and organelles.
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What is a reticulcyte?
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A premature RBC without a nuclei but with degrading organelles.
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What medication stimulates RBC production at multiple points on the pathway? What should be given in conjunction with it?
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Erythropoitin. Give with Iron.
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What are the three phases of RBC development? Describe each.
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1) Differentiation (from pluripotent stem cell to CFU-E)
2) Proliferation (from CFU-E to ejection of nuclei; multiple divisions occur) 3) Maturation (consists of reticulotyes and ends with mature RBC's) |
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What is the importance of glutathione?
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Absorbs the oxidative blow from oxidizing agents.
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How is glutathione regenerated?
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NADPH (from pentose shunt primarily but also from malate-pyruvate cycle) re-reduces glutathione and makes it ready to absorb another oxidizing blow.
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What is the important enzyme without which we would have very little NADPH to regenerate methionine to absorb oxidative stress?
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G6PDH, still would get some from malate-pyruvate shuttle but majority comes from pentose shunt.
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Met-Hb reduction is one unique reaction in RBC glycolysis. What is the other one?
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1,3 bisphosphoglycerate is mutated to 2,3 bisphosphoglycerate. 2,3 BPG helps to adjust the O2 sat curve for better performance at higher altitudes. 2,3 BPG is shunted back to glycolysis (Rapoport-Luebering shunt) as 3-phosphoglycerate in the next step.
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The Rapoport-Leubering shunt is one unique feature of RBC glycolysis. What is the other one?
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The reduction of cytochrome b5. Reduced cytochrome b5 goes on to reduce ferric methemoglobin (MetHb) to the normal ferrous state. MetHb is bad because it can't carry oxygen. MetHb builds up especially when methionine isn't reduced and able to take oxidative blows.
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What are the components of the RBC's cytoskeleton?
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-Spectrin
-Ankyrin -Band 3 protein -Actin -Provides for a flexible structure |
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What happens when there's a defect in a RBC's cytoskeleton?
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Decreases flexiblity and increases chance that RBC will be singled out for destruction by macrophages in the spleen.
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What are the four possible decorations that can be present on various porphyrins?
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-Methyls (M)
-Propionates (P) -Acetates (A) -Vinyls (V) |
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What groups do uroporphyrinogens contain?
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Acetates and Propionates
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What groups do coproporphyrinogens contain?
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Methyls and Vinyls
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What groups do protoporphyrinogens contain?
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Methyls, Vinyls, and Propionates
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What is the difference between a porphyrin and a porphyrinogen?
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Porphyrinogens don't have conjugated (alternating) double bonds and porphyrins do.
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How can you identify porphyrins in the blood or the urine?
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Porphyrins fluoresce in the Soret band. Have a red color.
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Where is heme synthesized?
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85% in the bone marrow and 15% in the liver.
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In the absence of globin, heme oxidizes to the Fe3+ ferric state. What effect does this have on heme synthesis?
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When heme is oxidized, it is called hemin or hematin. Hemin is an inhibitor of aminovulinic acid synthase (ALAS) because ALAS is the enzyme involved in the committed step of heme synthesis.
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How is ALAS (aminolevulinic acid synthase) inhibited by hemin?
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-Transcription inhibited (short half life of ALAS)
-Translation inhibited -Transport of ALAS into mitochondria inhibited |
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What causes ALAS (aminolevulinic acid synthase) to be increased in activity?
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-Cyt P450 enzymes being used, eg drug detox, steroid biosynthesis, etc.
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