Wednesday, September 17, 2008

Normal Human Hemoglobins and their Variants

Hemoglobin A (also designated as A1) represents 98% of the normal adult hemoglobin. It consists of four subunits, two alpha (α) and two beta (β) chains to form a quaternary protein designated as a tetramer. This molecule is not an enzyme but can behave as one. Its major function is to combine with oxygen forming oxyhemoglobin. Each subunit binds with one oxygen molecule. When dissociated from oxygen, it is designated as reduced hemoglobin. Hemoglobin A2 and makes up to 3% of the normal adult hemoglobin. It is composed of two (α) and two delta (δ)chains. This hemoglobin is increased in β-thalassemia.

Hemoglobin F makes up to 80% of the hemoglobin in the newborn (at birth). It appears about the third month of fetal life and persists as the dominant hemoglobin until birth. It is composed of two (α) and two gamma (γ) chains. The gamma chains are beta-like. At six months to one year of age, the F type hemoglobin has essentially been replace by A1 hemoglobin. In the adult individual, it will make up <1%>

Hemoglobin Portland. This is the third embryonic hemoglobin that forms early in embryonic life and disappears in early fetal life. It is composed of two zeta (ζ) chains and two gamma (γ) chains. Hemoglobin Gower II. This is the second embryonic hemoglobin that forms prior to hemoglobin Portland and disappears in the third month of fetal life. It is the most important of the embryonic hemoglobins, making up as much as 60% of the three embryonic types. It is made up of two α-globulin chains and two ε (epsilon)-globulin chains. It is found in severe alpha thalassemia.

Hemoglobin Gower I is found during the first two months of embryonic life and only in small quantities. It is made up of two ζ-globulins and two ε-globulins.

Letters of the Greek Alphabet

* Α, α = alpha I, ι = iota Ρ, ρ = rho
* Β, β/ = beta Κ, κ = kappa Σ, σ/ς = sigma
* Γ, γ = gamma Λ, λ = lambda Τ,τ = tau
* Δ, δ = delta Μ, μ = mu Υ, υ = upsilon
* Ε, ε = epsilon Ν, v = nu Φ, φ = phi
* Ζ, ζ = zeta Ξ, ξ = xi Χ, χ = chi
* Η, η = eta Ο, o = omicron Ψ, ψ = psi
* Θ, θ = theta Π, π, = pi Ω, ω = omega

This alphabet is provided for your information.

Other hemoglobin variants found in the normal adult are:

*Hemoglobin AIc which may make as much as 3.5% of the total adult hemoglobin. It is found in concentrations up to 30% (range = 8 to 30%) in diabetics. This is hemoglobin A1 that has undergone non-enzymatic glycosylation (with glucose via the Schiff reaction).
*Hemoglobin AIa is a hemoglobin A1 that is glycosylated with either fructose-1,6 phosphate molecule (AIa1) or a glucose-6-phosphate molecule (AIa2 ).

More about the glycosylated hemoglobin variant

Hgb A1, when bound to glucose, is called glycosylated hemoglobin. This phenomenon is dependent upon containing valine as a N–terminal amino acid on the beta chain. Glucose, if it makes contact with this terminal amino acid, will spontaneously bond in a non-enzymatic reaction to valine and form an aldimine or Schiff’s base. In this stage, this new intermediate form of hemoglobin is designated as “pre- Hgb AIc” and is somewhat unstable. This Schiff base will undergo a slow transformation (called the Amadori rearrangement) to form a ketoamine, a stable form of Hgb AIc. This process will occur throughout the life of the RBC.

The rate of Schiff base formation in the blood is blood glucose concentration dependent. In the normal individual, up to 8% of the hemoglobin (N: 5% to 8%) will be in the different forms of glycosylated hemoglobin (Hgb AIa, Hgb AIb, and Hgb AIc). An individual whose diabetes is under control will have an expected range of 8% to 15% glycosylated hemoglobin where the out-of-control diabetic may have a range of 15% to 30%.

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