Normal Hemoglobin Variants Normal Hemoglobin Variants are produced during different development stages depending on the genetic code of a human. If the person’s DNA fails to provide a proper code to produce the normal Hemoglobin Protein Chains, abnormal chains will be produced leading to constructing abnormal hemoglobin variants that may causes disease. We will speak here about the Normal Hemoglobin Variants. I have spoken previously about the benefits of having different Hemoglobin Variants and I mentioned that different Hemoglobin Variants normally have different functions during the different stages of development. I have also demonstrated how hemoglobin variant differ between each other based on their structure which depends on genetics at the first place. A hemoglobin molecule structure contains protein chains of amino acids. Different chains found in a hemoglobin molecule lead to giving the hemoglobin molecule its own unique biochemical and physical properties that differentiates it from molecules of other hemoglobin variants. If you are not familiar with how human genetics affect the structure of a hemoglobin molecule, I suggest you to read about “Genetics and structure of Hemoglobin Variants”.
Contents
Hemoglobin Levels
Normal Hemoglobin Levels
Normal Alternations to Hemoglobin Levels
Causes of Low Hemoglobin Levels
Causes of High Hemoglobin Levels
Hemoglobin Variants
Benefits of having different Hemoglobin Variants
Genetics and structure of Hemoglobin Variants
Normal Hemoglobin Variants
Embryonic Hemoglobin
Hemoglobin Gower 1
Hemoglobin Gower 2
Hemoglobin Portland 1
Hemoglobin Portland 2
Embryonic Hemoglobin is commonly known as Hemoglobin Epsilon or Hemoglobin ε. Embryonic Hemoglobin is the hemoglobin type found in a human embryo. When an ovum is finalized, the very first cell of a human is found, that cell is called a Zygote. After 30 hours of fertilization, the Zygote starts a long process of division to create larger number of cells known all together as Blastocyt. Even though the blastocyt has the same size of a zygote, its multiple cell help it to attache and implant into the Uterine Wall of the mother. The embryonic period of human begins when the blastocyte is completely implanted (approximately by the end of second week after fertilization) and ends approximately at the eighth week after fertilization.
Human body membranes are not found at the early stages of development. In other words, heart, brain, bone structure, liver, spleen and all other member are not found at the very first weeks after fertilization. Blood and blood vessels are not found at those early weeks, blood starts to appear as a group of unconnected spots known as Blood Islands. Blood is produced by the Yolk Sac at this early stage. The blood islands later expand and connect together to form an elementary network of blood vessels.
Studies suggest that Embryonic Hemoglobin can bind with Oxygen as well as Fetal and Adult Hemoglobin can do. However, unlike Fetal and Adult Hemoglobin, the properties and function of Embryonic Hemoglobin are still not highly defined. During the Embryonic Period, nutrition is provided in the form of yolk. In other words, blood is not what mainly transports nutrition to the body cells as it does later.
When a biological container is developed, it is not developed empty and filled later with its contents. Instead, a container in biology is usually developed with its contents. For this reason, I believe that blood vessels are created along with the embryonic blood as a foundation for functioning circulatory system at later stages.
Vitelline Circulation is a blood circulation that occurs between the Yolk Sac and the heart tubes of an embryo. It is believed that the blood carries nutrition from the yolk sac to rest of the embryo the same way blood does for fetus and adults. Also blood cells are produced in the yolk sac at this early stage and it is believed a supply of newly produced blood cells is taken from the yolk sac during this circulation.
Embryonic Hemoglobin is unstable and it breaks down easily. It also remains for a very short period of time and in a very low amounts that makes it difficult to study it as extensively as Fetal Hemoglobin and Adult Hemoglobin are studied. Like all types of hemoglobin variants, Embryonic Hemoglobin is also a tetramer ( a protein that its molecule is built up from four protein subunits). There are four types of Embryonic Hemoglobin or Hemoglobin Epsilon:
Hemoglobin Gower 1 (HbE Gower-1)
Hemoglobin Gower 1 is referred to as Fully Embryonic Hemoglobin because its molecule contains two Zeta (ζ) subunit chains and tow Epsilon (ε) subunit chains which are produced only during the embryonic period and not found normally in either Adult or Fetal Hemoglobin.
Zeta (ζ) subunit is an α-like hemoglobin subunit, which means it normally binds with Beta-like hemoglobin subunits in order to make up a hemoglobin molecule. The genetic coding for Zeta subunit is found in Chromosome 16 which also contains the genetic code for all Alpha-like hemoglobin subunits. Zeta subunit and the other alpha-like subunits belong to the same gene cluster known as Alpha-globin.
Epsilon (ε) subunit on the other hand, is a β-like hemoglobin subunit and it normally binds with Alpha-like hemoglobin subunits to make up a hemoglobin molecule. The genetic code for Epsilon is found in Chromosome 11 which is the some chromosome where the genetic code for all Beta-Like subunits is found. The Zeta chain genetic code is found along with the genetic code for other beta-like subunits in the 45 kb genetic cluster.
Both of Zeta chains and Epsilon chains are produced in the Yolk Sac only during the embryonic period. They both may be found in fetus after the eighth week, but their levels decease dramatically until their level be less than %1 at the 16th to the 25th weeks in a chromosomally normal fetus. In an abnormal fetus, it my take additional three to six weeks for Zeta and Epsilon subunits to be less than %1.
Hemoglobin Gower 1 has the biochemical code ζ2 ε2 because its molecular structure contains two Zeta chains and two Epsilon chains. It is also known as HbE Gower-1. Hemoglobin Gower 1 is also the primary type of embryonic hemoglobin and it is found in very levels during the embryonic period. However, Hemoglobin Gower 1 is highly unstable and it breaks down very quickly and doesn’t normally found in fetus after the embryonic period.
Hemoglobin Gower 2 (HbE Gower-2)
Hemoglobin Gower 2 or HbE Gower-2 is a Semi-Embryonic Hemoglobin because its molecule is made up of two Alpha (α) hemoglobin subunits and two Epslon (ε) hemoglobin subunits. While Epslon protein chains are synthesized in the Yolk Sac during the Embryonic Period only, Alpha protein chains are produced after the embryonic period in both fetus and adult. For this reason, half of protein chins in Hemoglobin Gower 2 molecules are embryonic subunits and the other half are not embryonic subunits. And this is where the name Semi-Embryonic Hemoglobin comes from.
Hemoglobin Gower 2if found in levels in the embryonic blood compared to Hemoglobin Gower 1 which is the primary embryonic hemoglobin. Also, in comparison to Hemoglobin Gower 1, Hemoglobin Gower 2 is more stable and it can stay in blood for longer time. HbE Gower-2 normally found in low levels in fetal blood and it can stay for few weeks after the end of embryonic period.
Hemoglobin Gower 2molecular structure is α2 ε2 and it may be used to treat condition of abnormal hemoglobin molecular structure as suggested by promising results from studying its effect on mice. Later, we will learn more about using normal hemoglobin variants to treat hemoglobin related conditions.
Hemoglobin Portland 1
Hemoglobin Portland 1 (a.k.a.HbE Portland-1) is another Semi-Embryonic Hemoglobin variant. Hemoglobin Portland 1 molecule contains two Zeta (ζ) subunits and two Gamma (γ) subunits. While Zeta subunits are mainly found in embryonic hemoglobin, Gamma subunits are mainly found in fetal hemoglobin (Hemoglobin F). Hemoglobin Portland 1 is semi-embryonic because it has both embryonic and fetal subunits.
Hemoglobin Portland 1is also unstable and it is found in low levels in embryo blood. Hemoglobin Portland 1 has the molecular structure code ζ2 γ2.
Hemoglobin Portland 2
Hemoglobin Portland 2 is also known as HbE Portland-2is also a Semi-Embryonic Hemoglobin variant. Hemoglobin Portland 2 has a molecular structure that includes both of the embryonic Zeta (ζ) subunits and the adult Beta (β) and it has the molecular structure of ζ2 β2.
Hemoglobin Portland 2 is very unstable and it doesn’t stay in fetus body for long time after the embryonic period.
Studies on mice has suggested the possibility of reactivating Hemoglobin Portland 2 in adults to treat some hemoglobin related condition. We will learn about reactivating embryonic hemoglobin and fetal hemoglobin later on.
Normal Hemoglobin Variants and Subunits: Molecules of Normal Hemoglobin Variants contain 4 normal protein subunits 2 subunits from Alpha-globin geneitc cluster and 2 subunits from the Beta-globin cluster. Each normal alph-globin chain is combined with each normal beta-globin chain to have a normal hemoglobin variant except for the Zeta chain and the Delta chain, they don’t normally combine together to create a normal hemoglobin variant. At the end we have 7 normal mutations of hemoglobin.
Contents
Hemoglobin Levels
Normal Hemoglobin Levels
Normal Alternations to Hemoglobin Levels
Causes of Low Hemoglobin Levels
Causes of High Hemoglobin Levels
Hemoglobin Variants
Benefits of having different Hemoglobin Variants
Genetics and structure of Hemoglobin Variants
Normal Hemoglobin Variants
Embryonic Hemoglobin
Hemoglobin Gower 1
Hemoglobin Gower 2
Hemoglobin Portland 1
Hemoglobin Portland 2
Embryonic Hemoglobin (Hemoglobin ε)
Embryonic Hemoglobin is commonly known as Hemoglobin Epsilon or Hemoglobin ε. Embryonic Hemoglobin is the hemoglobin type found in a human embryo. When an ovum is finalized, the very first cell of a human is found, that cell is called a Zygote. After 30 hours of fertilization, the Zygote starts a long process of division to create larger number of cells known all together as Blastocyt. Even though the blastocyt has the same size of a zygote, its multiple cell help it to attache and implant into the Uterine Wall of the mother. The embryonic period of human begins when the blastocyte is completely implanted (approximately by the end of second week after fertilization) and ends approximately at the eighth week after fertilization.
Human body membranes are not found at the early stages of development. In other words, heart, brain, bone structure, liver, spleen and all other member are not found at the very first weeks after fertilization. Blood and blood vessels are not found at those early weeks, blood starts to appear as a group of unconnected spots known as Blood Islands. Blood is produced by the Yolk Sac at this early stage. The blood islands later expand and connect together to form an elementary network of blood vessels.
Studies suggest that Embryonic Hemoglobin can bind with Oxygen as well as Fetal and Adult Hemoglobin can do. However, unlike Fetal and Adult Hemoglobin, the properties and function of Embryonic Hemoglobin are still not highly defined. During the Embryonic Period, nutrition is provided in the form of yolk. In other words, blood is not what mainly transports nutrition to the body cells as it does later.
When a biological container is developed, it is not developed empty and filled later with its contents. Instead, a container in biology is usually developed with its contents. For this reason, I believe that blood vessels are created along with the embryonic blood as a foundation for functioning circulatory system at later stages.
Vitelline Circulation is a blood circulation that occurs between the Yolk Sac and the heart tubes of an embryo. It is believed that the blood carries nutrition from the yolk sac to rest of the embryo the same way blood does for fetus and adults. Also blood cells are produced in the yolk sac at this early stage and it is believed a supply of newly produced blood cells is taken from the yolk sac during this circulation.
Embryonic Hemoglobin is unstable and it breaks down easily. It also remains for a very short period of time and in a very low amounts that makes it difficult to study it as extensively as Fetal Hemoglobin and Adult Hemoglobin are studied. Like all types of hemoglobin variants, Embryonic Hemoglobin is also a tetramer ( a protein that its molecule is built up from four protein subunits). There are four types of Embryonic Hemoglobin or Hemoglobin Epsilon:
Hemoglobin Gower 1 (HbE Gower-1)
Hemoglobin Gower 1 is referred to as Fully Embryonic Hemoglobin because its molecule contains two Zeta (ζ) subunit chains and tow Epsilon (ε) subunit chains which are produced only during the embryonic period and not found normally in either Adult or Fetal Hemoglobin.
Zeta (ζ) subunit is an α-like hemoglobin subunit, which means it normally binds with Beta-like hemoglobin subunits in order to make up a hemoglobin molecule. The genetic coding for Zeta subunit is found in Chromosome 16 which also contains the genetic code for all Alpha-like hemoglobin subunits. Zeta subunit and the other alpha-like subunits belong to the same gene cluster known as Alpha-globin.
Epsilon (ε) subunit on the other hand, is a β-like hemoglobin subunit and it normally binds with Alpha-like hemoglobin subunits to make up a hemoglobin molecule. The genetic code for Epsilon is found in Chromosome 11 which is the some chromosome where the genetic code for all Beta-Like subunits is found. The Zeta chain genetic code is found along with the genetic code for other beta-like subunits in the 45 kb genetic cluster.
Both of Zeta chains and Epsilon chains are produced in the Yolk Sac only during the embryonic period. They both may be found in fetus after the eighth week, but their levels decease dramatically until their level be less than %1 at the 16th to the 25th weeks in a chromosomally normal fetus. In an abnormal fetus, it my take additional three to six weeks for Zeta and Epsilon subunits to be less than %1.
Hemoglobin Gower 1 has the biochemical code ζ2 ε2 because its molecular structure contains two Zeta chains and two Epsilon chains. It is also known as HbE Gower-1. Hemoglobin Gower 1 is also the primary type of embryonic hemoglobin and it is found in very levels during the embryonic period. However, Hemoglobin Gower 1 is highly unstable and it breaks down very quickly and doesn’t normally found in fetus after the embryonic period.
Hemoglobin Gower 2 (HbE Gower-2)
Hemoglobin Gower 2 or HbE Gower-2 is a Semi-Embryonic Hemoglobin because its molecule is made up of two Alpha (α) hemoglobin subunits and two Epslon (ε) hemoglobin subunits. While Epslon protein chains are synthesized in the Yolk Sac during the Embryonic Period only, Alpha protein chains are produced after the embryonic period in both fetus and adult. For this reason, half of protein chins in Hemoglobin Gower 2 molecules are embryonic subunits and the other half are not embryonic subunits. And this is where the name Semi-Embryonic Hemoglobin comes from.
Hemoglobin Gower 2if found in levels in the embryonic blood compared to Hemoglobin Gower 1 which is the primary embryonic hemoglobin. Also, in comparison to Hemoglobin Gower 1, Hemoglobin Gower 2 is more stable and it can stay in blood for longer time. HbE Gower-2 normally found in low levels in fetal blood and it can stay for few weeks after the end of embryonic period.
Hemoglobin Gower 2molecular structure is α2 ε2 and it may be used to treat condition of abnormal hemoglobin molecular structure as suggested by promising results from studying its effect on mice. Later, we will learn more about using normal hemoglobin variants to treat hemoglobin related conditions.
Hemoglobin Portland 1
Hemoglobin Portland 1 (a.k.a.HbE Portland-1) is another Semi-Embryonic Hemoglobin variant. Hemoglobin Portland 1 molecule contains two Zeta (ζ) subunits and two Gamma (γ) subunits. While Zeta subunits are mainly found in embryonic hemoglobin, Gamma subunits are mainly found in fetal hemoglobin (Hemoglobin F). Hemoglobin Portland 1 is semi-embryonic because it has both embryonic and fetal subunits.
Hemoglobin Portland 1is also unstable and it is found in low levels in embryo blood. Hemoglobin Portland 1 has the molecular structure code ζ2 γ2.
Hemoglobin Portland 2
Hemoglobin Portland 2 is also known as HbE Portland-2is also a Semi-Embryonic Hemoglobin variant. Hemoglobin Portland 2 has a molecular structure that includes both of the embryonic Zeta (ζ) subunits and the adult Beta (β) and it has the molecular structure of ζ2 β2.
Hemoglobin Portland 2 is very unstable and it doesn’t stay in fetus body for long time after the embryonic period.
Studies on mice has suggested the possibility of reactivating Hemoglobin Portland 2 in adults to treat some hemoglobin related condition. We will learn about reactivating embryonic hemoglobin and fetal hemoglobin later on.
Normal Hemoglobin Variants and Subunits: Molecules of Normal Hemoglobin Variants contain 4 normal protein subunits 2 subunits from Alpha-globin geneitc cluster and 2 subunits from the Beta-globin cluster. Each normal alph-globin chain is combined with each normal beta-globin chain to have a normal hemoglobin variant except for the Zeta chain and the Delta chain, they don’t normally combine together to create a normal hemoglobin variant. At the end we have 7 normal mutations of hemoglobin.
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