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CPR Final Exam > Erythrocyte Biochemistry > Flashcards

Erythrocyte Biochemistry Flashcards

1
Q

What makes up fetal hemoglobin?

A
  • 2 alpha
  • 2 gamma
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2
Q

What makes up adult hemoglobin type A?

A
  • 2 alpha
  • 2 beta
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3
Q

What makes up adult hemoglobin type A2?

A
  • 2 alpha
  • 2 delta
  • only makes up 3%
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4
Q

Describe the structure of hemoglobin?

A
  • tetramer
  • one heme per subunit
  • Has ferrous iron
  • carries oxygen
  • hydrophobic
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5
Q

What happens to hemoglobin once oxygen binds?

A
  • Before o2 binds iron is outside the plane of porphyrin
  • Once it binds it moves into the plane of heme
  • The change pulls down the proximal histiidine of Hb and changes interaction assoc with globin chain
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6
Q

What will the ODC look like for myoglobin vs hemoglobin?

A
  • Myoglobin is hyperbolic
  • Hemoglobin is sigmoidal due to interactions between globin subunits (+ coorperativity, binding of one oxygen facilitates binding of next and so on)
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7
Q

Where is the steepest part of ODC and what is the significance?

A
  • It is between 40 torr which is pO2 at rest and 20 torr which is during exercise
  • It indicates that Hb is very efficient during exercise with providing oxygen to tissues
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8
Q

What does 2,3-BPG do to the ODC?

A
  • reduces oxygen’s affinity so hemoglobin will give up oxygen easier to tissues
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9
Q

How does the Bohr effect modify the ODC?

A
  • CO2 and H are by products of actively respiring tissues, this enhances the oxygen delivery/release from hemoglobin
  • pH of active tissue drops from 7.4 to 7.2
    • This drops the binding affinity of Hb for O2
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10
Q

Compare Fetal ODC and Mother ODC.

A
  • Oxygen flows from mom to baby
  • The gamma subunits have higher affinity than the beta for oxygen so the baby will not let it go as easy
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11
Q

What mutation causes SCA?

A
  • Glutamic acid changes to valine at position 6 in the beta chain
  • This causes polymerization of Hb and sickle shaped RBC’s which impede circulation and cause hemolytic anemia
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12
Q

How is iron regulated?

A

By modulating its absorption

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13
Q

What is ferritin?

A
  • Protien that will bind ferric iron to help store it
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14
Q

What happens to ferrous iron when it enters an enterocyte?

A
  • It gets oxidized to ferric iron by ferroxidase (Cerruloplasmin)
  • It gets stored as ferritin and degraded to homosiderin
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15
Q

How is non heme iron (Fe3) absorbed stored and transported?

A
  • Plant products are difficult to absorb
  • They get converted to Fe2 by ferric reductase (Dcytb) in the presence of vitamin C
  • Fe2 will enter the enterocyte via divalent transporter 1 (DMT1)
  • Gets converted to Fe3 by ferroxidase for storage or exported out via ferroportin
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16
Q

What does ferroportin require to function?

A
  • Needs hephaestin for function
  • Ferroportin levels are regulated by hepcidin
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17
Q

What protein binds Fe3 for transport to target tissues?

A

Transferrin

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18
Q

How does uptake of transferrin occur?

A
  • Via receptor mediated endocytosis with transferrin receptor
  • It gets internalized with clathrin coated pits into endosomes and the low pH of endosomes releases transferrin from the receptor
  • Iron gets taken up in mitochondria when the endosome docks and transfers it via DMT1 this is where heme is made
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19
Q

What happens when hepcidin binds ferroportin?

A
  • It causes internalization of ferroportin and its degradation in lysosomes
  • It will bind when iron content is too high
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20
Q

What regulates hepcidin?

A
  • complex signaling path involving transferrin, receptor and a protein called human homeostatic iron reguolator protein
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21
Q

When iron is high, hepcidin expression goes ___, ferroportin levels go ____, and iron absorption is now ____.

A

When iron is high, hepcidin expression goes up, ferroportin levels go down, and iron absorption is now decreased.

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22
Q

When iron is low, hepcidin expression goes ___, ferroportin levels go ____, and iron absorption is now ____.

A

When iron is low, hepcidin expression goes up, ferroportin levels go up, and iron absorption is now high.

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23
Q

Iron deficiency slilde 195

A
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24
Q

what is hereditary hemochromatosis?

A
  • Increased absorption of iron which accumulates in the heart, liver, and pancreas
  • It causes liver cirrhosis, hepatocellulalr carinoma, diabetes, arthritis and heart failure
  • Auto recessive mutation in HFE
25
Q

What does a deficiency of folalte and B12 cause?

A
  • megaloblastic macrocytic anemia due to decreased syntheiss of DNA in developing RBC bone marrow
  • characterized by large erythrocytes
26
Q

Describe folate metabolism.

A
  • folate gets reduced to DHF by DHF reductase
  • DHF gets reduced to THF via DHF reductase
  • THF is the active form and important for synthesis of purines and pyrimidine thymine
  • Serves a vital role in DNA synthesis
27
Q

How long does the storage of folate last?

A

3-6 months in the liver

28
Q

What is the primary active form of THF in the blood?

A
  • Folic acid gets reduced to N5-methyl-THF once absorbed into the intestine
29
Q

What is methotraxate?

A
  • Binds to DHF reductase and inhibits it
  • It is an antineoplastic agen that will inhibit DNA synthesis
30
Q

What happens to THF if B12 isn’t available?

A
  • Folate trap occurs, as the B12 is a methyl acceptor and creastes Methyl-B12 and releases THF
31
Q

How is B12 absorbed?

A
  • Dietary B12 will bind to R-binder proteins
  • Intrinsic factor made by parietal cells degrade R binder proteins in duodenum releasing B12
  • IF carries B12 to ileium where it gets released in blood
  • IF-Cobalamin is carried by Transcobalamin II in the blood and getss taken up by cells throug hreceptor mediated endocytosis
32
Q

What is pernicious anemia?

A
  • B12 deficiency can occur due to lack of IF, leads to a megaloblastic macrocytic anemia
33
Q

What is the Schilling test?

A
  • Used to figure out cause of Pernicious anemia
  • Give radioactive Coalbamin and collect urine for 24 hrs looking for the radioactive B12
    • if present it means normal absorption of B12 and the deficiency is in the diet
    • If absent B12 isnt absorbed so pernicious anemia
  • From pernicious anemia you give another dose of radioactive B12 PLUS IF
  • Collect urine for 24 hours and if radioactive B12 is present its pernicious anemia due to lack of IF
34
Q

What are the two key features of porphyrin rings?

A
  • Four 5 membered rings with nitrogen
  • Iron in ferrous state
  • Oxidation to ferric state inactivates hemoglobin
35
Q

Where does biosynthesis of heme occur?

A
  • liver and erythroid cells of bone marrow
36
Q

Where do phases one two and three of heme synthesis occur?

A
  • Mitochondria
  • Cytosol
  • Mitochondria
  • Defects in any stage causes porphyrias
37
Q

What happens in phase one of heme synthesis?

A
  • Within the mitochondria delta aminolevulinic acid is synthesized from glycine and succinyl coenzyme A
  • It gets released from the Mitochondria
  • ALA Synthase
38
Q

What happens in phase two of heme synthesis?

A
  • In the cytosol condensation of two delta ALAs form porphobilinogen (PB)
  • Condensation of four PBs assemble the tetrapyrrole ring of coproporphyrinogen III
39
Q

What happens in phase three of heme synthesis?

A
  • Two oxidation reactions of coproporphyrinogen III to install side chain vinyll groups in protoporphyrinogen IX and make fully ocnjugated ring of protophorphyrin IX
  • insertion of Fe2 with ferrochelatase
40
Q

Succinyl CoA + GLycine=___? This also requires what vitamin?

A

ALA is made and it requires B6 (PLP)

41
Q

What does lead inhibit within the heme synthesis pathways?

A
  • ALA dehydratase and ferrochelatase
    • ALA is neurotoxic it contributes to the neuro sx of lead poisioning
    • Heme production lowered
    • Causes microcytic and hypochromic anemia
42
Q

What are porphyrias?

A
  • inherited metabolic disorders caused by defects in heme synthesis
  • Purple pigment
  • Can be acute hepatic or erythropoietic
    • hepatic-neuro sx
    • erythropoietic-photosensitivity
43
Q

A defect in PBG deaminase in the liver will lead to ____.

A
  • Acute intermittent porphyria
  • It is auto dominant
  • Deficiency leads to excessive production of ALA and PBG resulting in periodic attacks of ab pain and neuro dysfxn
  • Hepatic
44
Q

Uroporphyrinogen III synthase defect results in what condition?

A
  • Congenital Erythropoietic porphyria
  • Results in build up of Uroporphyrinogen I and its oxidation product of uroporphyrin I
  • Produces red color in urine, teeth, and destroys RBC and causes skin photosensitivity
45
Q

What is “Celebrity Porphyrias”?

A
  • Variegate porphyria
  • Includes intermittent episodes of abdomen pain, delirium, hallucinations, convulsions
46
Q

what does heme oxygenase do?

A
  • Clips heme and opens up the ring into a linear form to make biliverden
47
Q

What does biliverdin reductase do?

A
  • Adds two protons to biliverdin to make bilirubin
48
Q

How do we get conjugated bilirubin from unconjugated and what does this do?

A
  • add two glucuronate acid to bilirubin with Bilirubin UDP glucuronyltransferase
  • Makes bilirubin more soluble
49
Q

When bilirubin is released to blood what occurs after all the way to the end?

A
  • It complexes with albumin and travels to liver where it gets conjugated with UDP glucuronyltransferase
  • conjugated/direct bilirubin-diglucuronide goes to gall bladder
  • galll bladder releases it to SI and it gets converted into bilirubin and then microbiota makes urobillinogen
  • Urobillinogen either gets reabsorbed and converted in kidneys to urobilin OR not reabsorbed and converted into sterocobilin in LI and excreted as feces
50
Q

What is jaundice?

A
  • hyperbilirubinemia
  • Elevated levels of BR in blood stream
  • It is an imbalance btw production and excretion of bilirubin
51
Q

What is a pre-hepatic jaundice?

A
  • Increased production of unconjugated BR
  • Excess hemolysis
  • Internal hemorrhage can cause this as well as maternal fetal incompatibility
  • Problem occurs before liver
52
Q

What is intra hepatic jaundice?

A
  • Impaired hepatic uptake conjugation or secretion of ocnjugated BR
  • Can be causaed by general hepatic dysfxn
    • Criggler-Najjar syndrome
    • Gilbert syndrome
    • Liver cirrhosis
    • Viral hepatitis
53
Q

What is post hepatic jaundice?

A
  • AKA Cholestatic jaundice or cholestasis
  • Problems with BR excretion caused by:
    • cholangiocarcinoma
    • gall stones
    • Liver disease
    • drugs
    • obstruction to bile drainage
  • Conjugated BR in the urine so dark urine
  • Pale stool
54
Q

Complete UDP-GT deficiency?

A
  • Criggler Najjar syndrome
  • Type one is complete absent of the gene resulting in severe hyperbilirubinemia causeing kernicturus
  • Tx:
    • blood transfusion
    • phototherapy
    • heme oxygenase inhibitors
    • liver transplant
55
Q

Mutation in UDP GT gene?

A
  • Criggler Najar syndrome type II
  • enzyme has about 10% activity
56
Q

Gilbert syndrome?

A
  • Common benign disorder resuts from reduced UDP GT
    • 25% activity
    • fasting stress or alcohol can increase BR
57
Q

What is hepatitis?

A
  • Inflammation of liver leading to dysfunction
  • Caused by virus, alcoholic cirrhosis, or cancer
  • Increased levels of unconjugated and conjugated BR in the blood
58
Q

What is neonatal jaundice?

A
  • Called Physiological jaundice
  • Immature hepatic metabolic paths unable to conjugate and excrete bilirubin
  • Deficiency of UDP GT enzyme bc not mature yet
  • Breakdown of fetal hemoglobin as its replaced with adult

CPR Final Exam (16 decks)

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