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41 Cards in this Set

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Structure of heme?
What is heme?
Component of hemoglobin, myoglobin, and some cytochromes.
Consists of porphyrin ring which is bound to single iron atom.
Heme Function
Iron atom in its ferrous (Fe2+) binds to Oxygen and transports it. In the Fe3+ form it WILL NOT bind Oxygen.
Affinity of CO to heme
Higher affinity to heme iron than oxygen
What molecule is responsible for protecting heme from oxidizing agents
Glutathione (a tripeptide) reduces oxidizing agents which neutralizes them.
How is glutathione regenerated?
When 2 glutathione-SH groups are oxidized to form glut-S S-glut.......... they are then re-reduced to two Glutathione molecules using NADPH e*
How is NADPH regenerated after being oxidized?
NADP+ is re-reduced to NADPH via the PENTOSE PHOSPHATE PATHWAY
What is the PPP?
Pentose phosphate pway. Glucose-6-Phosphate -> 5-carbon sugars (HMP shunt)
What enzyme return iron to 2+ state?
Methemoglobin reductase
MHb Reductase rxtn?
MHbheme Fe3 > Fe2...... NADH > NAD+....... Glycolysis re-reduces resulting NAD > NADH
Rxtn can only correct minor amount of heme iron oxidation.
MHb reductase
What portion of heme is not recylced?
Porphyrin ring breaksdown into bilirubin like products that must be removed from body
Heme synthesis?
Where does heme synthesis occur?
Reticulocytes, hepatocytes, other cells synth. heme Fe proteins
Materials for heme synth?
Succinyl CoA (fromTCA cycle)
Glycine
Fe2+
What enzymes regulates heme synth? Cofactors?
Aminolevulinic acid synthase(ALA) requires B6
Regulation of ALA synthase?
Feedback inhib. by heme
What genes does heme regulate?
Alpha and Beta chains of Hb
ALA synthase
What enzymes do lead inhibit in the heme syn pway?
Lead inhibits ALA dehydratase and ferrochelatase.
Affects of lead on the synth?
Anemia and problems with energy production due ot lack of heme-containing cyt for ox phos
What do genetic defects that effect enzymes in the pathway called?
Porphyrias (rare disorders)
Is excess dietary iron absorbed?
no
Where does iron storage occur?
Liver
Is blood loss major source of iron loss?
yes
What proteins are involved in iron transport?
Transferrin
Ferritin
Hemosiderin
Transferrin function?
Transports fe in bloodstream
What is the TIBC?
Would it rise during iron deficiency?
Total iron binding capacity (plasma) due mainly to free (non iron bound) transferrin
Ferritin function?
Assists in gut absorption and SHORT TERM storage Plasma ferritin level usually correlate directly with body iron supply
Hemosiderin function?
LONG TERM storage
What is fate of Porp ring of heme?
Catabolized to conjugated bilirubin ofr excretion via GI tract. Iron and globin AA are recylced
Where is unconjugated bilirubin first produced?
Produced from porp ring in RE cells including SPLEEN.
How is uncon-indirect bilirubin transported in the blood?
Bound to albumin.
What enzyme acts on bilirubin when it reaches the liver?
Glucuronyl transferase.
What is bilirubin diglucuronide? How is it formed?
Conjugated form of bilirubin. Hepatic conjugation occurs and Glucuronyl transfersase uses Activated UDP-glucoronate substrate.
How is bilirubin diglucoronide excreted?
Excreted via the gall bladder.

Bacterial action converts to urobilinogen and stercobilin in the intestine.
What is juandice?
Elevated serum bilirubin.
Can result from prehepatic, hepatic, or posthepatic abnormalities
Bilirubin can be in two forms:
Indirect-Uncon (albumin bound)
and
Direct-Conj
How is bilirubin measured?
Chromophore dye binds with conjugated bilirubin and is quantitaed spectrophotometrically
Total bilirubin Measured- direct bilirubin Measured=??
indirect bilirubin (unconjugated) It has to be calculated because it can't be measured because it's bound to albumin.
High amount of indirect bilirubin indicates what pathology?
Pre-hepatic or hepatic-pre conjugation pathology
High direct bilirubin pathology?
Post-hepatic or hepatic-post conjugation