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MCP Unit 3 > Heme Degradation > Flashcards

Heme Degradation Flashcards

1
Q

Heme catabolism

A
  • lifetime of RBC-120 days
  • 9 billion destroyed daily
  • tracked radioactive glycine to figure out
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2
Q

removal of RBCs

A
  • in spleen
  • liver and bone marrow can
  • reticular endothelial cells engulf through phagocytosis
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3
Q

hemoglobin break down

A
  • globin is broken down to amino acids

- heme is broken down into iron which is recycled, and the rest of the ring is broken down and digeted

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4
Q

three steps to heme breakdown

A
  • break the ring
  • reduce the broken ring (both in reticular endothelial cells)
  • conjugate to sugars to make it water soluble-in liver
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5
Q

haptoglobin

A

binds methemoglobin dimers (iron in ferric state)

in case of destruction away from spleen and liver

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6
Q

hemepexin

A
  • binds free heme

- incase breakdown other than spleen and liver

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7
Q

transferrin

A
  • binds free iron

- in case of destruction away from spleen or liver

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8
Q

hemolytic anemias

A

-10% of red cell destruction in plasma

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9
Q

heme degradation

A
  • heme to biliverden (breaks ring and uses 02 and NADPH)
  • biliverden to bilirubin
  • conjugation of bilirubin
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10
Q

heme oxygenase

A
  • heme to biliverden
  • catalyzes the rupture of the methylidyne group of heme between the pyrrole rings carrying vinyl groups
  • bridging carbon removed as CO
  • 1% of hemoglobins binding sites have CO
  • spleen, ER
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11
Q

bilirubin

A
  • easily passes through PM b/c it is lipid soluble
  • diffuses into bloodstream and binds with serum albumin and transported to liver
  • major antioxidant
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12
Q

biliverden reductase

A
  • uses NADPH
  • biliverdento bilirubin
  • in spleen
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13
Q

conjugation of bilirubin

A
  • bilirubin-albumin into liver, transferred to bilirubin ligandin
  • made water soluble by adding two UDP-glucaronic acids (from glycogen) to P side chains (one each)
  • forms bilirubin diglucaronide (conjugated bilirubin) which is secreted in the bile
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14
Q

glucuronyl bilirubin transferase

A

-transfers two gluronic acids from UDP gluronic acid to the P side chains

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15
Q

Crigler-Najjir syndrome

A

-deficiency in UDP glucuronyl transferase-severe jaundice because bilirubin around

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16
Q

neonatal jaundice

A
  • production of insufficient UDP glucuronyl transferase by the infant
  • temporary
  • phototherapy
  • irradiated bilirubin breakdown products are more soluble than bilirubin and can be excreted by the liver into the bile without conjugation
17
Q

conjugated bilirubin

A
  • passes from liver into bile canaliculi, to gall bladder,to the GI tract
  • bacteria convert it to urobilinogens and related products
  • some urobilinogen reabsorbed into portal system, then re excreted into bile, some leaves via the kidney
  • oxidation of urobilinogen leads to urobilin, which gives color to urine and feces
18
Q

prehepatic jaundice

A
  • massive breakdown of red blood cells resulting in overproduction of free bilirubin
  • liver cells can’t conjugate bilirubin at the rate it enters the liver, get build up of unconjugated in blood
  • sickle cell, MVA
  • no conj bili, normal AST and ALT, normal ALP, no uring bilirubin, but there is urine urobilinogen
19
Q

hepatic jaundice

A
  • can’t conjugate or deposit
  • diseased condition of the liver (hepatitis, cirrhosis), that prevents the uptake or conjugation of bilirubin
  • both conj and unconj in blood
  • high conj, high AST, ALT, normal ALP, has both urine bilirubin and urobilinogen
20
Q

post-hepatic jaundice

A
  • blockage of bile flow out of the liver and into the intestinal tract, build up of conj
  • gal stones, pancreatic cancer
  • high conj, normal AST/ALT, high ALP, urine bilirubin, no urine urobilinogen
21
Q

iron storage

A
  • ferritin and hemosiderin
  • ferritin can contain 4500 atoms in a reversible manner
  • hemosiderin is degraded form of ferritin
  • increased in iron=increase in ferritin
  • most reserve in liver, bone marrow, skeletal muscles, spleen
  • can get iron tox in transfusion patients
22
Q

transferrin

A
  • takes Fe from spleen to marrow (RBCs take it the other way)
  • glycoprotein synthesized in liver that it plasma localized
  • protein and receptor recycled
  • keeps serum levels low and is antimicrobial
23
Q

absorption of iron by receptor mediated endocytosis

A
  1. ferro-transferrin binds receptor on cell membrane at pH 7
  2. receptor and ligand are taken up in clathrin coated pits
  3. pH in the vesicle is lowered to 5 which makes iron dissociate
  4. receptor and apotransferrin are returned to PM where pH is 7 and transferrin no longer binds

Fe3+ binds to transferrin well at pH 7
apotransferrin releases receptor at pH 7

MCP Unit 3 (8 decks)

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