Mod.A. Bio Lec6: Hemoglobin

Question 1

basic structure of Hb

Answer 1

1- four globin polypeptide chains
(بس خلي بالك two pairs of dissimilar globins.) * أي أنه : * heterotetramer (α2β2)
Each polypeptide chain has a helical structure, each with heme group.

2- The iron ((Fe2+ to bind O2 reversibly ) of each heme group is bound by
coordination bonds to nitrogen atoms of imidazole rings of histidine amino acids

Question 2

where is Hb present ?
weight
count

Answer 2

only found in the cytoplasm of erythrocytes (RBCs)

comprise almost one third of the weight of a red cell

280 million Hb molecules are carried in one RBC

Question 3

main function

Answer 3

1- transport O2 from lungs to tissues and CO2 from the tissues to the lungs.
2- Hemoglobin Buffering system

Question 4

Haem & globin produced at two different sites in the cells:

Answer 4

haem in mitochondria

globin in ribosomes

Question 5

Steps of heme synthesis:

Answer 5

1- Synthesis of ALA
2- Synthesis of porphobilinogen
3-incorprating iron

Question 6

ALA synthesis (site ,substrate used enzyme, co enzymes)

Answer 6

in mitochondria ( لماذا ؟؟؟ )
السبب This reaction is energy dependent

* Two starting materials : succinyl-CoA (citric acid cycle) and Glycine

* الإنزيم المستخدم : ALA
synthase

need pyridoxal phosphate as activator of glycin

Question 7

What is the rate limiting step of heme synthesis ?

Answer 7

ALA synthase

Question 8

Porphobilinogen synthesis (site, how, used enzyme)

Answer 8

لمكان : ALA leaves the mitochondria → cytoplasm

* ما يتم في التفاعل : 2x ALA condense together to form porphobilinogen (PBG)

• الإنزيم المستخدم : porphobilinogen synthase (=ALA dehydratase)

Question 9

incorporating iron

Answer 9

By ferrochelatase

Question 10

Heme synthesis (location , substrate , mediated by, regulatory enzyme)

Answer 10

Organ location: in bone marrow (85% of Hb) and
liver (mainly for the synthesis of the cytochrome P450 class of enzymes that
are involved in detoxification )

*intracellular location: mitochondria/cytoplasm/mitochondria
مهم synthesis of heme starts in mitochondria

• substrates: succinyl-CoA + glycine + Fe2+
• Mediated by : erythropoietin ( EPO ) and vitamin B6
• key regulatory enzyme : ALA synthase

Question 11

regulation of ALA synthase

Answer 11

inhibited by
1- an end product-heme
(feedback inhibition) ,
2- glucose and steroids

activated by:
stimulated by certain drugs as phenobarbital and iron.

Question 12

ALA dehydratase (porphobilinogen synthase) is inhibited by

Answer 12

lead

Question 13

ferrochelatae is inhibited and activated by

Answer 13

inhibited by lead ions Pb2+.

• Its activity is influenced by availability of Fe2+ and ascorbic acid.

Question 14

Lead poisoning (type, result, symptoms)

Answer 14

Acquired

Inhibits enzyme involved in heme biosynthesis (PBG synthase & ferrochelatase).

Irritability , Poor appetite, Lethargy, Abdominal pain

Question 15

Porphyrias (type, cause, result. symptoms)

Answer 15

(hereditary

abnormality of the enzymes which synthesize heme
(e.g., PBG Synthase, Porphobilinogen Deaminase, etc…)

1- leads to accumulation of intermediates of the pathway (“porphyrins” or “porphyrin precursors” ) خاصة Elevated 𝛿-aminolevulinic acid (ALA)
2- a deficiency of heme → 3- excretion of heme precursors in feces or urine, giving them a dark 4- red color accumulation of porphyrinogens in the skin can lead to photosensitivity
5- affected primarily in liver or in developing erythrocytes. 6-the neurological symptoms
7- abdominal pain 8- nerve damage and even death 9- formation of superoxide radicals.

Photosensitivity, abdominal pain, neuropsychiatric symptoms

Question 16

The binding of the first O2
to Hb enhances the binding
futher O2 molecules

allosteric affect?

Answer 16

Hb binds O2 weakly at low oxygen pressures

Hb binds O2 tightly at high pressures

Question 17

Hb can exist in 2 different forms:

Answer 17

R-form and T-form.

Question 18

Oxyhemoglobin exists in

Answer 18

the R state

increased affinity for O2 = Oxygen causes rupture of some bonds.

Question 19

Deoxyhemoglobin exist in

Answer 19

T state

reduced affinity for O2 = 4subunits are packed by ionic and H-bond

Question 20

Carbaminohemoglobin is formed when

Answer 20

T-state Hb react with CO2

Question 21

15% of CO2 are transported to the lungs as

Answer 21

hemoglobin carbamate

Question 22

85% of CO2

Answer 22

transported as bicarbonate

Question 23

2,3diphosphoglycerate (formation, functon)

Answer 23

Formation of 2,3diphosphoglycerate in RBCs by the enzyme 2,3-BPG mutase

binds with greater affinity to deoxygenated hemoglobin

Question 24

fetal HB has high O2 affinity, why ?

Answer 24

Fetal Hb has less 2,3-diphosphoglycerate than adult HB

Question 25

What is HbA1C

Answer 25

Non-enzymatic glycated adult Hb-form constitutes has glucose residues attached to β-globin chains يعني is glycosylated (5-8%)

Question 26

increased amount of HbA1C is found in

Answer 26

patients with diabetes (reaches 12%)

Question 27

importance of HbA1C

Answer 27

could be used as a monitor for the control of the blood glucose level during the last 2 months for diabetic patients.

Question 28

Abnormal derivative of Hb:

Answer 28

1- Methemoglobin (Met-Hb) : It is an oxidized Hb ,where Fe is present in the ferric state. بمعنى contains Fe3+ instead of Fe2+ in heme groups. It Binds O2 irreversibly, is unable to act as an O2 carrier, oxidation (Fe2+Fe3+) caused by H2O2, free radical, drugs, and pollution 2-Carboxylhemoglobin (COHb): – CO binds to Fe2+ in heme in case of CO poisoning or smoking. - CO has 200x higher affinity to Fe2+ than O2left-shifted O2-Hb curve. - Conc of COHb above 40% unconsciousness fatal 3-Sulfhemoglobin (S-Hb) Hb: - combining with sulfur, results from exposure of Hb to the toxic effects of certain drugs as sulfonamides. - S-HB produces anoxia because it can not act as O2 carrier 4- Hematin: is Hb without iron (i.e. protoporphyrin combining with globin).