Hemes

Question 1

What is the Heme structure?

Answer 1

A porphyrin ring (4 linked pyrrole rings) with a central Fe

Question 2

What cell types have the ability to make Heme?

Answer 2

Mostly bone/liver but all cells have some capacity

Question 3

What are some enzymes/functions of Heme?

Answer 3

hemoglobin, cytochromes, COX, NOS, NADPH oxidase, catalase, peroxidases

Question 4

What is the first reaction in Heme synthesis?

Answer 4

glycine + succinyl CoA –> d-aminolevulinate

Question 5

What enzyme completes the first step of heme synthesis? What are its cofactors, what regulates it?

Answer 5

d-aminolevulinate synthase. Coenzyme: pyridoxal phosphate. Regulation: Heme production

Question 6

What is the second step of heme synthesis? What enzyme does this step and what inhibits this enzyme?

Answer 6

two d-ALA mocules combine to form phorphobilinogen. d-ALA dehydrogenase. inhibited by lead.

Question 7

How many molecules of glycine and succinyl CoA are required to make one Heme molecule?

Answer 7

8

Question 8

What enzyme completes Heme synthesis? What does it do? What inhibits this enzyme?

Answer 8

ferrochetalase inserts Fe into the protoporphyrin IX. Lead inhibits this enzyme.

Question 9

What are porphyrias?

Answer 9

defects in enzymes involved in heme synthesis

Question 10

What two enzymes does lead inhibit?

Answer 10

d-ALA dehydrogenase and ferrochetalase

Question 11

What are the major and minor sites of RBC degradation?

Answer 11

spleen (major), liver (minor)

Question 12

What do hemopaxin and haptoglobulin do?

Answer 12

bind and carry free heme in the circulation, thereby preventing the fenton reaction

Question 13

What is the first step of heme degradation? what enzyme does this reaction?

Answer 13

Heme is oxidized to biliverdin by heme oxygenase

Question 14

What is the second step of heme degradation?

Answer 14

Biliverdin is reduced to bilirubin

Question 15

What is the third step of heme degradation?

Answer 15

bilirubin is transported to the liver by serum albumin

Question 16

What is the fourth step of heme degradation? where does it occur?

Answer 16

occurs in the liver- bilirubin is conjugated to glucoronate and secreted into the bile (a Phase 2 reaction!)

Question 17

What happens to bilirubin diglucoronide in the intestines?

Answer 17

hydrolyzed to free bilirubin

Question 18

What happens to the free bilirubin in the intestines?

Answer 18

converted by bacteria to urobiligens and stercobilins that are then excreted in the feces

Question 19

What amount of heme is normaly degraded per day? What is the maximum?

Answer 19

300 mg/day. max is 3,000 mg/day

Question 20

What is a source of CO in the blood and where does it go?

Answer 20

from heme oxygenase in the heme degradation first step. The CO is blown off or used as a vasodilator

Question 21

What can bilirubin function as?

Answer 21

an endogenous antioxidant

Question 22

What is prehepatic jaundice?

Answer 22

excess RBC destruction, overwhelming the heme degradation capacity –> bilirubin accumulation. (can occur in infants with a high RBC turnover rate)

Question 23

What is hepatic jaundice?

Answer 23

from liver conditions that interfere with bilirubin uptake or conjugation (also in infants that have low-levels of this enzyme)

Question 24

What enzyme does bilirubin conjugation in the liver?

Answer 24

bilirubin gluconuronyl transferase

Question 25

What is posthepatic jaundice?

Answer 25

physical bile obstruction that prevents bile from reaching the intestines (cholecystitis, eg.)

Question 26

What protein carries two Fe in circulation? where is it made?

Answer 26

transferrin, made in the liver

Question 27

is transferring often fully saturated?

Answer 27

No, usually only 20-45% saturated

Question 28

What protein binds 2000-4500 Fe and stores it in the liver?

Answer 28

ferritin

Question 29

What is hemosiderin?

Answer 29

a protein aggregate formed with high iron intake, consists of protein granules, polysaccharide and Fe3+

Question 30

what is the average daily Fe intake? daily Cu intake?

Answer 30

Fe: 15 mg/day; Cu: 1.3 mg/day

Question 31

How is Fe generally lost?

Answer 31

passively

Question 32

How does Vitamin C affect Fe absorption in the intestines?

Answer 32

increased iron absorption by 10-15%

Question 33

What is ceruloplasmin?

Answer 33

carries Cu in the blood

Question 34

What vitamins/minerals are needed for catecholamine synthesis?

Answer 34

Cu, Vitamin C, B6

Question 35

What amino acid is a major catecholamine precursor?

Answer 35

Tyrosine

Question 36

What are some examples of catecholamines?

Answer 36

melanin, dopamine, L-Dopa, thyroxine (thyroid hormones), Epi/Norepi

Question 37

What is the first step of catecholamine synthesis? What enzyme is involved, what does it require?

Answer 37

hydroxylation of tyrosine to L-Dopa. enzyme: tyrosine hydroxylase. requires: NADPH and tetrahydrobiopterin

Question 38

What is the rate-limiting step in catecholamine synthesis?

Answer 38

The first step, formation of L-Dopa from tyrosine

Question 39

What is the second step of catecholamine synthesis? What enzyme completes this step and what is required?

Answer 39

L-Dopa –> dopamine.
Enzyme: aromatic hydrocarbon decarboxylase
Requires: pyridoxal phosphate (B6)

Question 40

What is the third step of catecholamine synthesis? What enzyme completes this step and what is required?

Answer 40

dopamine –> norepinephrine
Enzyme: dopamine b-hydroxylase
Requires: Cu2, Vit C, O2

Question 41

What is the fourth step of catecholamine synthesis? What is the enzyme that completes this step? What induces this step? What inhibits this step?

Answer 41

norepinephrine –> epinephrine
Enzyme: phenylethanolamine N-methyltransferase
Induced by glucocorticoids
Inhibited by epinephrine

Question 42

Where does the synthesis of catecholamines occur?

Answer 42

neurons in the adrenal medulla

Question 43

What two steps form melanins from tyrosine in melanocytes?

Answer 43

tyrosine –> dopa (via tyrosine hydroxylase) –>melanins (albinism inhibits these two steps)