Biochemistry Heme Metabolism

Front 1

Structure of heme?

Back 1

Front 2

What is heme?

Back 2

Component of hemoglobin, myoglobin, and some cytochromes.
Consists of porphyrin ring which is bound to single iron atom.

Front 3

Heme Function

Back 3

Iron atom in its ferrous (Fe2+) binds to Oxygen and transports it. In the Fe3+ form it WILL NOT bind Oxygen.

Front 4

Affinity of CO to heme

Back 4

Higher affinity to heme iron than oxygen

Front 5

What molecule is responsible for protecting heme from oxidizing agents

Back 5

Glutathione (a tripeptide) reduces oxidizing agents which neutralizes them.

Front 6

How is glutathione regenerated?

Back 6

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*

Front 7

How is NADPH regenerated after being oxidized?

Back 7

NADP+ is re-reduced to NADPH via the PENTOSE PHOSPHATE PATHWAY

Front 8

What is the PPP?

Back 8

Pentose phosphate pway. Glucose-6-Phosphate -> 5-carbon sugars (HMP shunt)

Front 9

What enzyme return iron to 2+ state?

Back 9

Methemoglobin reductase

Front 10

MHb Reductase rxtn?

Back 10

MHbheme Fe3 > Fe2...... NADH > NAD+....... Glycolysis re-reduces resulting NAD > NADH

Front 11

Rxtn can only correct minor amount of heme iron oxidation.

Back 11

MHb reductase

Front 12

What portion of heme is not recylced?

Back 12

Porphyrin ring breaksdown into bilirubin like products that must be removed from body

Front 13

Heme synthesis?

Back 13

Front 14

Where does heme synthesis occur?

Back 14

Reticulocytes, hepatocytes, other cells synth. heme Fe proteins

Front 15

Materials for heme synth?

Back 15

Succinyl CoA (fromTCA cycle)
Glycine
Fe2+

Front 16

What enzymes regulates heme synth? Cofactors?

Back 16

Aminolevulinic acid synthase(ALA) requires B6

Front 17

Regulation of ALA synthase?

Back 17

Feedback inhib. by heme

Front 18

What genes does heme regulate?

Back 18

Alpha and Beta chains of Hb
ALA synthase

Front 19

What enzymes do lead inhibit in the heme syn pway?

Back 19

Lead inhibits ALA dehydratase and ferrochelatase.

Front 20

Affects of lead on the synth?

Back 20

Anemia and problems with energy production due ot lack of heme-containing cyt for ox phos

Front 21

What do genetic defects that effect enzymes in the pathway called?

Back 21

Porphyrias (rare disorders)

Front 22

Is excess dietary iron absorbed?

Back 22

no

Front 23

Where does iron storage occur?

Back 23

Liver

Front 24

Is blood loss major source of iron loss?

Back 24

yes

Front 25

What proteins are involved in iron transport?

Back 25

Transferrin
Ferritin
Hemosiderin

Front 26

Transferrin function?

Back 26

Transports fe in bloodstream

Front 27

What is the TIBC?
Would it rise during iron deficiency?

Back 27

Total iron binding capacity (plasma) due mainly to free (non iron bound) transferrin

Front 28

Ferritin function?

Back 28

Assists in gut absorption and SHORT TERM storage Plasma ferritin level usually correlate directly with body iron supply

Front 29

Hemosiderin function?

Back 29

LONG TERM storage

Front 30

What is fate of Porp ring of heme?

Back 30

Catabolized to conjugated bilirubin ofr excretion via GI tract. Iron and globin AA are recylced

Front 31

Where is unconjugated bilirubin first produced?

Back 31

Produced from porp ring in RE cells including SPLEEN.

Front 32

How is uncon-indirect bilirubin transported in the blood?

Back 32

Bound to albumin.

Front 33

What enzyme acts on bilirubin when it reaches the liver?

Back 33

Glucuronyl transferase.

Front 34

What is bilirubin diglucuronide? How is it formed?

Back 34

Conjugated form of bilirubin. Hepatic conjugation occurs and Glucuronyl transfersase uses Activated UDP-glucoronate substrate.

Front 35

How is bilirubin diglucoronide excreted?

Back 35

Excreted via the gall bladder.

Bacterial action converts to urobilinogen and stercobilin in the intestine.

Front 36

What is juandice?

Back 36

Elevated serum bilirubin.
Can result from prehepatic, hepatic, or posthepatic abnormalities

Front 37

Bilirubin can be in two forms:

Back 37

Indirect-Uncon (albumin bound)
and
Direct-Conj

Front 38

How is bilirubin measured?

Back 38

Chromophore dye binds with conjugated bilirubin and is quantitaed spectrophotometrically

Front 39

Total bilirubin Measured- direct bilirubin Measured=??

Back 39

indirect bilirubin (unconjugated) It has to be calculated because it can't be measured because it's bound to albumin.

Front 40

High amount of indirect bilirubin indicates what pathology?

Back 40

Pre-hepatic or hepatic-pre conjugation pathology

Front 41

High direct bilirubin pathology?

Back 41

Post-hepatic or hepatic-post conjugation