Heme Biochemistry

Front 1

What form of heme molecule is found in hemoglobin and myoglobin?

Back 1

Heme b

Front 2

What molecule contains the iron that binds to the oxygen in oxygen transport storage proteins?

Back 2

heme b

Front 3

Where is heme C found?

Back 3

In cytochrome C

Front 4

Where is cytochrome C found?

Back 4

It is an important molecule in the ETC and in the mitochondria, as well as apoptosis.

Front 5

Where does the majority of heme synthesis take place?

Back 5

In erythroid cells

Front 6

What form of heme is found in the majority of your body?

Back 6

heme b

Front 7

Where does the majority of heme synthesis take place besides in the erythroid cells?

Back 7

In the liver

Front 8

Where does most of the heme synthesized by the liver end up?

Back 8

In the cytochrome p450 superfamily of monooxygenases.

Front 9

What does cytochrome p450 do?

Back 9

Degrades different classes of molecules and plays a role in the degradation of drugs/pharmacoagents

Front 10

What amino acid contributes all of its carbons and nitrogens to heme?

Back 10

Glycine

Front 11

What molecule only contributes carbons to the heme backbone?

Back 11

Acetate

Front 12

What molecule contributes all of its molecules to the functional component of heme?

Back 12

Glycine

Front 13

What is the difference b/e porphyrins and heme?

Back 13

The presence of iron, porphyrin do not have iron. SO if you took a porphyrin and added Fe then you created heme.

Front 14

What forms the coordination sites for the Fe atom in heme?

Back 14

The four pyrrole rings w/ their nitrogen. The four nitrogens point towards the middle to form the coordination sites for Fe.

Front 15

What determines the different versions of heme? (heme b, heme c, etcetera)

Back 15

The different substituents off of the pyrrole rings in the larger porphyrin ring.

Front 16

What class of diseases are caused by defects in heme synthesis?

Back 16

Porphyrias

Front 17

What molecule is the result of heme degradation?

Back 17

bilirubin.

Front 18

What disease is caused by the accumulation of bilirubin in peripheral tissues?

Back 18

jaundice

Front 19

What are the two starting substrates in heme synthesis?

Back 19

Acetate and Glycine

Front 20

What molecule can be used to make succinyl CoA?

Back 20

Acetyl CoA

Front 21

Where in the cell does the first reaction in heme synthesis take place?

Back 21

In the mitochondrial matrix

Front 22

Where in the cell does the majority of heme synthesis take place?

Back 22

In the cytosol.

Front 23

What reaction forms the pyrrole rings of porphyrin?

Back 23

The second reaction where 8 Aminolevulinate (ALA)goes to 4 porphobilinogen (BPG)

Front 24

Where in the cell does the final part of heme synthesis take place?

Back 24

In the mitochondrial intermembrane space

Front 25

What is another name for heme?

Back 25

protoporphyrin IX

Front 26

What is the last step in heme synthesis?

Back 26

Addition of Fe

Front 27

What regulates heme synthesis in hepatocytes?

Back 27

heme, it functions in a negative feedback loop.

Front 28

Where is the transporter for heme located?

Back 28

In the outer-mitochondrial membrane, even though this membrane is porous heme is just too big and too polar to go through.

Front 29

What cells in the body need to transport heme OUT of their cytosols?

Back 29

Hepatocytes

Front 30

What cells in the body need to transport heme INTO their cytosol?

Back 30

Cells that are not capable of heme synthesis, but that still require heme in their mitochondria.

Front 31

Where in the cell does heme really like to be? why do we care?

Back 31

It likes to sit in the membranes when it is not bound to a protein, this is important b/c it has an Fe bound to it and it can damage proteins and generate ROS. So free heme can really damage membranes.

Front 32

What cells is the ALAS1 gene expressed in?

Back 32

Constitutively expressed in all cells

Front 33

What cells constitutively express ALAS2?

Back 33

Erythroid cells

Front 34

What heme synthesis enzyme is embedded in the innermitochondrial membrane?

Back 34

ALA synthase so the catalytic portion is located in the mitochondrial matrix, but it has an outer portion in the intermembrane space that heme can bind to and inhibit.

Front 35

What effect do insulin or glucose have on heme synthesis?

Back 35

They inhibit peroxisome proliferator-activated receptor 1 (PGC-1) which is an activator of ALAS-1.

Front 36

What effect do glucagon or fasting have on heme synthesis?

Back 36

They activate PGC-1 alpha transcription factor which activates ALAS1

Front 37

What effect does lead have on heme synthesis?

Back 37

"Lead Poisoning" inhibits the last step of heme synthesis (where Fe is added)as well as the second step (where the pyrrole rings are formed)

Front 38

What is one of the consequences of Lead Poisoning?

Back 38

Porphyrias b/c it inhibits lead synthesis.

Front 39

What are the major clinical manifestations of acute porphyrias?

Back 39

Neurologic effects

Front 40

What are the major clinical manifestations of cutaneous porphyrias?

Back 40

Photosensitivity

Front 41

What tissues are the major sources where porphyria intermediate overproduction occurs?

Back 41

1. Hepatic
2. Erythropoietic

Front 42

What clinical symptoms do the majority of the erythroid porphryias have?

Back 42

Cutaneous symptoms

Front 43

What is the major clinical feature of porphyria cutanea tarda (PCT)?

Back 43

Skin photosensitivity to sunlight exposure resulting in sores/blisters and their urine is discolored to look like wine or tea

Front 44

What enzyme deficiency causes acute intermittent porphyria?

Back 44

A defect in hydroxymethylbilane synthase

Front 45

What accumulates in acute intermittent porphryia?

Back 45

Porphobilinogen (PBG) and delta-amino-levulinic acid (ALA)

Front 46

What is the characteristic sequence of symptomatic events that is seen in acute intermittent porphyria?

Back 46

1. abdominal pain
2. psychiatric symptoms, i.e. hysteria
3. peripheral neuropathy, mainly motor neuropathy.

Front 47

What enzyme deficiency causes erythropoietic protophyria (EPP)?

Back 47

Ferrochelatase deficiency in erythropoietic cells

Front 48

What accumulates in erythropoietic protophyria?

Back 48

Protoporphyrin leading to cutaneous photosensitivity and hepatobiliary disease

Front 49

What porphyria can have both cutaneous and hepatic manifestations?

Back 49

Erythropoietic protophyria

Front 50

Elevated levels of what enzyme signal liver disease?

Back 50

ALT/AST

Front 51

Where does breakdown of heme to bilirubin take place?

Back 51

In macrophages

Front 52

Where is heme oxygenase located?

Back 52

Inside macrophages

Front 53

What does heme oxygenase do?

Back 53

Breaks heme apart into biliverdin using NADPH.

Front 54

Where in heme degradation is CO produced?

Back 54

In the first step where heme is broken down to biliverdin by heme oxygenase

Front 55

Where is bilirubin produced?

Back 55

In macrophages

Front 56

What protein does bilirubin bind to in circulation?

Back 56

Albumin

Front 57

What happens to bilirubin in the liver?

Back 57

It is conjugated to UDP-glucuronic acid to form bilirubin diglucuronide

Front 58

What happens to bilirubin diglucuronide?

Back 58

It is secreted into the bile

Front 59

What is bilirubin diglucuronide turned into if it is secreted in stool?

Back 59

Urobilinogen (which has a brownish color and is largely responsible for the color of stool)

Front 60

What will Sy will pts have if they have a inability to conjugate bilirubin to UDP-glucuronic acid?

Back 60

They will have stool that is whitish and not brown.

Front 61

What is ultimately responsible for the color of human waste (both feces and urine)?

Back 61

Heme

Front 62

What is the direct bilirubin measurement?

Back 62

- The reaction w/o accelerator (alcohol)
- Considered the measure of conjugated bilirubin

Front 63

What is the total bilirubin measurement?

Back 63

Measures the reaction w/ accelerator (alcohol) since bilirubin is hydrophobic and not soluble this solubilizes unconjugated bilirubin so it can measure all bilirubin in the body. Then you subtract the conjugated bilirubin number and you get the amount of unconjugated bilirubin.

Front 64

What can cause normal, healthy, people to look like they have jaundice?

Back 64

Carrots

Front 65

What causes hemolytic jaundice?

Back 65

An acute situation causing RBCs to lyse, which causes more bilirubin to be synthesized than the Liver can handle, so the excess bilirubin accumulates in peripheral tissue.

Front 66

How can Liver dz cause jaundice?

Back 66

They are making normal amounts of bilirubin but the pt simply cannot conjugate it to UDP-glucuronic acid. So again, bilirubin accumulates in peripheral tissues and the pt gets jaundiced.

Front 67

How can you distinguish b/e Liver jaundice and hemolytic jaundice and mechanical jaundice (caused by Gallstones)?

Back 67

Hemolytic: There will be elevated levels of indirect/unconjugated bilirubin

Liver: There will be elevated levels of direct/conjugated bilirubin and normal levels of indirect/unconjugated bilirubin

Gallstone: normal level of unconjugated and high levels of conjugated

Front 68

What enzyme is low in newborns and can cause neonatal jaundice?

Back 68

UDP-glucuronyl transferase

Front 69

What is newborn phototherapy?

Back 69

The photons can modify bilirubin to form structural isomers that are more soluble or favor the oxidation of bilirubin.