HEMOGLOBIN

Formation:
- Takes place in the developing red cells located in the bone marrow
- Requires 1 week after which It occupies 1/3 of the red cell. The other 2/3 of
the R.C. is mostly water.
Components of Hemoglobin:
• 4 molecules of the
nitrogenous substance
Protoporphyrin IX
• 4 iron atoms in the ferrous
state
• Protein component →
Globin → composed of 2
sets of 2 different
polypeptide chains.
• One 2,3 Diphosphoglycerate
(2,3 – DPG) molecule as a
sometime resident in the
center of the Hb unit.

2,3 – DPG
- A substance produced in the
Anaerobic Glycolytic (EMBDEN – MEYERHOF) pathway. This pathway
generates energy for the erythrocyte
- When Hb binds 2,3 – DPG, O2 affinity decreases. When plasma level of 2,3 –
DPG decreases, Hb 2,3 – DPG is released and the Hb affinity for O2 increases.
- Adequate tissue oxygenation requires among other factors, adequate supplies Globin Production like all protein synthesis entails
of 2,3 – DPG to encourage Hb to release O2 to the tissues. 4 Basic Phases:
• Transcription – production of pre-mRNA
HEME PRODUCTION and STRUCTURE:
• Processing – formation of the final mRNA
- Heme production requires the formation of Protoporphyrin IX and the
• Translation – mRNA leaves the nucleus for a ribosome in the
availability of Iron.
cytoplasm.
Heme Synthesis:
• Transfer - tRNA is required to collect the amino acids from the
- Requires a sequence of steps all of which are enzymatically directed.
cytoplasm and carry them to the appropriate site on the ribosome.
- Occurs most abundantly in the erythroid precursors
Main Function of Hb
GLOBIN CHAIN PRODUCTION
- Transport oxygen from the lungs
- Globin chains are simple (nonconjugated) proteins consisting of amino acids
- Oxygen tension in pulmonary capillaries = 100 mm Hg
only
- 95-98% of Hb combined with oxygen
- The chains are designated by the Greek letter α,β,γ,δ,ε & ζ
- Oxygen Tension in Tissues = 20 mm Hg
- Less than 30% combined with oxygen
Normal Hb variants:
- Embryonic hemoglobins (during the first three months after conception) 1. HEMIGLOBIN or METHEMOGLOBIN (Hi)
a. Portland (ζ2γ2) - Ferrous iron is oxidized to the ferric state resulting in the inability of Hi to
b. Gower I (ζ2ε2) combine reversibly with oxygen
c. Gower II (α2ε2) - Up to 1.5% of the Hb is Hi in the normal individual
- Fetal hemoglobin (4th month of embryonic development till birth) (α2γ2) - Increase of Hi will cause cyanosis & functional anemia
- Adult hemoglobin (one year & older) - Can be reduced back to Hb by the erythrocyte enzyme system
HbA1, or HbA (α2β2) – 97% of Hb, HbA2 (α2δ2) - 2. SULFHEMOGLOBIN (Shb)
approx. 2% of Hb - Mixture of oxidized, partially denatured forms of Hb that form during
- Hb variants, normal & abnormal may be identified by electrophoresis. oxidative hemolysis
- During oxidation of Hb, sulfur is incorporated into the heme rings of Hb
LOCATIONS OF HEMOGLOBIN during FUNCTION and resulting in a green hemochrome
DEGRADATION: - Further oxidation results in the denaturation and precipitation of Hb as HEINZ
- Except during fetal life, Hb is formed in the bone marrow bodies.
- It is synthesized inside the developing erythrocytes from the stage of - Can’t transport O2 but it can combine with CO2 to form
basophilic erythroblast (prorubricyte) until shortly after erythrocyte release into CARBOXYSULFHEMOGLOBIN
the circulation. - Can’t be reduced back to Hb and it remains in the cells until they break down.
- On erythrocyte destruction the cell remnants are captured by phagocytic cells - Has been reported in patients receiving treatment with sulfonamides or
of the RES, mostly spleen and liver but also the bone marrow. aromatic amine drugs (phenacetin, acetanilid)
- Hb degradation in the RES causes the release of iron, globin and biliverdin 3. CARBOXYHEMOGLOBIN (HbCO)
- Iron and globin chain amino acids are recycled for use in Hb synthesis, where - Endogenous carbon monoxide (CO) produced in the degradation of heme to
as biliverdin is degraded and excreted. bilirubin accounts for 0.5% (CO) in the blood and is ↑ in hemolytic anemia.
- Hb has the capacity to combine w/ CO 210X greater than the affinity for O2
REMNANTS OF HEME PRODUCTION: (CO will bind with Hb even if its concentration in the air is extremely low (0.02
- Normally, at the completion of heme synthesis, there is a small amount of to 0.04%)
excess porphyrin in the mitochondrion that is complexed to zinc. This is called - HbCO will build up until typical symptoms of poisoning appear
“Free Erythrocyte Protoporphyrin” (FEP) - Death will result if blood becomes more than 40% saturated (acute CO
• FEP in the erythrocytes is elevated when the iron is diminished poisoning)
• FEP can be measured in the laboratory for diagnosis of certain - Cant bind oxygen
disorders. - Chief sources of CO:
• ↑FEP → lead poisoning & iron deficiency > Gasoline motors, gas heaters, defective stoves, illuminating
- FERRITIN aggregates are also found normally in the cytoplasm; and these are gas,
visible microscopically after staining with PRUSSIAN BLUE. They represent tobacco smoking
storage iron that was not used in heme synthesis. - Chronic poisoning – a result of prolonged exposure to small amounts of CO
4. CARBAMINOHEMOGLOBIN (HbCO2)
HEMOGLOBIN DERIVATIVES - Hemoglobin + carbon dioxide
Physiologic Hemoglobins - Occurs in the lungs
a.) –Oxyhemoglobin - 10-23% of CO2 is carried in the blood
b.) –Reduced hemoglobin - 70% is converted as bicarbonate
Are readily converted into a series of compounds through the action of acids, - 7-10% of CO2 is free state in plasma
alkalies, oxidizing and reducing substance, heat and other agents.