Heme Synthesis

Question 1

4 pyrrole rings

Answer 1

Porphyrins

Question 2

Porphyrins + metal ions

Answer 2

Metalloporphyrins

Question 3

Reduced porphyrins

Answer 3

Phorphorynogen

Question 4

Heme + proteins

Answer 4

Hemoproteins

Question 5

Biosynthesis of heme ring occurs in the

Answer 5

mitochondria and cytosol

Question 6

Heme is synthesized from

Answer 6

Succinyl CoA

Glycine

Question 7

Examples of hemoproteins

Answer 7

Hemoglobin CYP450
Myoglobin catalase
Cytochrome c Tryptophan pyrrolase

Question 8

Needed to activate glycine

Answer 8

Pyridoxal phosphate

Question 9

Rate limiting step in Heme Synthesis

Answer 9

ALA Synthase

Question 10

Occurs in all cells due to the requirement for heme as a prosthetic

Group of enzymes and electron transport chain proteins

Answer 10

Heme Synthesis

Question 11

Major locations of heme synthesis

Answer 11

Liver (CYP450)

Erythroid progenitor cells (hemoglobin)

Question 12

Integral or Intrinsic Proteins

Answer 12

Band 3

Glycophorin

Question 13

Peripheral or Extrinsic Proteins

Answer 13

Spectrin
Actin
Protein 4.1

Question 14

Two forms of Quarternary Structure of Hemoglobin

Answer 14

R (relaxed) form

T (taut) form

Question 15

Binds oxygen several hundred times more readily than T form

Increase in this form shifts the curve to the left

Answer 15

R relaxed form

Question 16

Ends of b chains form salt bridges stabilizing it

Reduced affinity for oxygen

Inc in this form shifts the curve to the right

Ex

Answer 16

T (tense) form

Chlorophyll
Heme of hemoglobin

Question 17

Inc acidity

Dec pH

Answer 17

Shift to the right

Bohr effect

Question 18

Inc Partial pressure of CO2

HCO3 leaves the RBCs into plasma

Answer 18

Shift to the right

Bohr effect

Question 19

When HCO3 leaves the RBCs into the plasma and HCO3 is replaced by Cl

Answer 19

Chloride shift

Question 20

Inc in temperature

Answer 20

Shift to the right

Bohr effect

Question 21

Hypothermia

Answer 21

Shift to the left

Haldane

Question 22

Inc 2,3 DPG

Answer 22

Shift to the right
Bohr effect

One DPG molecule binds to each Hb and stabilizes T form promoting O2 release

Question 23

Has affinity for Hb 200x that of oxygen

Once bound, does not dissociate

Answer 23

Carbon monoxide

Question 24

Binds only to methemoglobin
Prevents reduction to active form
Impairs ability of blood to transport O2

Answer 24

Cyanide

Question 25

Genetic disorders of heme metabolism | Can also be acquired by intake of

Answer 25

Porphyrins Lead

Question 26

6 major types Classified on the basis of the organs or cells that are most affected Major sites are RBC and liver Photosensitivity and neurologic problems

Answer 26

Pophyria

Question 27

Photosensitivity (blistering of skin when exposed to sunlight) Hypertrichosis Oncholysis Most common subtype of porphyria Named because it is a porphyria that presents with skin manifestations later in life

Answer 27

Porphyria cutaneous tarda

Question 28

Porphyria cutaneous tarda is a problem with this enzyme

Answer 28

Uroporphyrinogen decarboxylase (UROD)

Question 29

Abdominal pain | Neuropsychiatric symptoms

Answer 29

Acute intermittent porphyria

Question 30

Acute intermittent porphyria is caused by deficiency of this enzyme

Answer 30

Uroporphyrinogen I synthase

Question 31

During fasting, lactate from RBC and exercising muscle is converted in the liver to glucose that is returned to RBC and muscle

Answer 31

Cori Cycle

Question 32

Muscle releases alanine delivering both gluconeogenic subtrate and an amino group for urea synthesis

Answer 32

Alanine cycle

Question 33

Porphyria tx

Answer 33

Avoid drugs that cause induction of CYP450 Photosensitivity administer beta carotene Sunscreen

Question 34

How many erythrocytes are destroyed in 1 day

Answer 34

200B

Question 35

70kg human daily turnover of heme

Answer 35

6g hemoglobin

Question 36

Globin is degraded into

Answer 36

Amino acids and reused

Question 37

Iron during heme catabolism

Answer 37

Goes back to iron pool

Question 38

Porphyrin goes to the

Answer 38

Reticuloendothelial cells (liver, spleen, bone marrow)

Question 39

Enzyme that catalyzes breakdown of heme

Answer 39

Heme oxygenase

Question 40

End product of heme metabolism

Answer 40

Bilirubin

Question 41

1g hemoglobin yields

Answer 41

35 mg bilirubin

Question 42

Daily bilirubin formation

Answer 42

250-350 mg

Question 43

Early product of catabolism and on reduction yields bilirubin

Answer 43

Biliverdin

Question 44

Formed in peripheral tissues | Transported to liver by plasma albumin

Answer 44

Bilirubin

Question 45

How is bilirubin metabolized

Answer 45

Uptake of bilirubin by liver parenchymal cells Conjugation of bilirubin with glucoronate in the ER Secretion of conjugated bilirubin