HEMA 1_LEC 4_Hemoglobin PDF

LESSON 4: Hemoglobin COMPLEX STRUCTURE— TETRAMER LECTURER: Mary Theres M. Famador, RMT It is considered complex because it is made up of 4 units...

LESSON 4: Hemoglobin COMPLEX STRUCTURE— TETRAMER LECTURER: Mary Theres M. Famador, RMT It is considered complex because it is made up of 4 units of monomers. I. HEMOGLOBIN ○ Two (2) alphas One of the most studied proteins. ○ Two (2) betas ○ Mainly because it is very easy for us to isolate Each unit is made up of heme and globin. hemoglobin from your RBCs. Since it has 4 units, hemoglobin is usually referred to as MAIN FUNCTION being a tetramer. 1 To transport oxygen from the lungs to tissue. ○ Also having a quaternary structure. 2 To transport carbon dioxide from the tissues to the lungs. Contributes to the Acid-Base Balance by binding and by LECTURER’S NOTES: 3 releasing hydrogen ions to transport nitric oxide. Its function is very important and very necessary since our body requires oxygen for it to function properly / for us to survive. HEMOGLOBIN COMPROMISES: 1 Compromises 95% Cytoplasmic content of RBC. RBC contains mostly your Hemoglobin. RBCs don't have any organelles (ex: mitochondria, Endoplasmic Reticulum), just mostly hemoglobin. 1 RBC can contain approximately 270 Million (270,000,000) of biomolecules of Hemoglobin. 1 Hemoglobin can carry up to 4 oxygen molecules. One Globin is made up of one peptide chain. ○ If you calculate that, (270 Million x 4), it computes to ○ Consists of 4 globin chains and is usually grouped around 1 Billion; you can just imagine how into two identical pairs (two alphas and two betas) in efficiently can 1 RBC contain a significant amount a normal adult. of oxygen. Heme portion that is made up of iron located in the 2 RBC provides protection to HgB. middle of the ring of protoporphyrin. Protection in two ways: 1. Denaturation of hemoglobin. ○ Meaning the hemoglobin is outside the RBC. II. HEME ○ Its life span will decrease ↓ and it can protect A. HEME STRUCTURE when there is denaturation. 2. When it passes to the kidney. 3 Properties Concentration: 34 g/dl. Molecular weight: around 64,000 daltons. A. HEMOGLOBIN STRUCTURE Heme structure Hemoglobin Structure (Blue: Globin/ Peptide Chain; Green: Heme portion; Red: Oxygen) Protoporphyrin ring Refers to what makes up hemoglobin and how it looks like. The protoporphyrin ring in the heme structure is the one In the picture, it shows that it is usually depicted and that is surrounding the green area (Ferrous Iron atom). described as a globular protein with very complex Made up of different atoms structure. ○ Such as carbon atoms and nitrogen atoms. This transcript is strictly confidential and is intended for AVR 5TH FLOOR group members only; please don’t share or distribute! 1  HEMATOLOGY 1 | Lesson 4: Hemoglobin The ring has no amino acids, which is why the Product: Uroporphyrinogen III protoporphyrin ring is also known as your prosthetic group. 5 Uroporphyrinogen III In the center of this protoporphyrin ring is your ferrous iron. Catalyst: Uroporphyrinogen decarboxylase ○ Ferrous iron is 2+ Product: Coproporphyrinogen III Oxygen only combines in the FERROUS (2+) state BACK IN THE MITOCHONDRIA of iron. 6 Coproporphyrinogen III (in cytoplasm) ○ Ferric iron is 3+ Catalyst: Coproporphyrinogen oxidase B. HEME BIOSYNTHESIS Product: Protoporphyrinogen IX This refers to how heme is created or being produced. ○ This product will be back in the mitochondria It involves the mitochondria and the cytoplasm/cytosol. 7 Protoporphyrinogen IX Occurs in the mitochondria and cytoplasm of bone marrow Catalyst: Protoporphyrinogen Oxidase ○ Mitochondria - powerhouse of the cell. Product: Protoporphyrin IX ○ Cytoplasm - holds the internal components of the cell in 8 Protoporphyrin IX place. Then through the catalyzation of Ferrochelatase/Heme A mature RBC – NO organelles Synthase with the addition of Fe++ (Ferrous Iron), this ○ It does not have a mitochondria and a cytoplasm. will form: Heme biosynthesis does not happen in your mature 9 Heme RBCs. Final Product ○ RBCs in the circulation cannot make a heme, only PICTURE FROM RODAK’S: those erythrocyte precursors (pronormoblast up to erythrocyte), which can be found in the bone marrow Locations on when they take place: ○ Mitochondria - 1st (initial) and last 3 steps ○ Cytoplasm - intermediate/ middle steps Heme Biosynthesis Pathway LECTURER’S NOTES: Heme Biosynthesis Mnemonic: PorH UR Cop Proto a cup of Heme Heme Biosynthesis Pathway III. GLOBIN HEME BIOSYNTHESIS in the RBC Precursors INITIAL STEP: MITOCHONDRIA A. GLOBIN STRUCTURE 1 Succinyl-CoA + Glycine Catalyst: ALA Synthase Cofactor: Vitamin B6 (Pyridoxine) ○ It is a limiting step, hence the need for this cofactor. ○ Purpose: binds to the enzyme to help the reaction Product: ALA (condensation of succinyl-coenzyme A + glycine) CYTOPLASM 2 ALA (in mitochondria) Catalyst: ALA dehydrase 4 Globin Chains that make up 1 Hemoglobin Product: Porphobilinogen (PBG) ○ Product will be in cytoplasm. One hemoglobin is made up of 4 Globin chains. 3 Porphobilinogen (PBG) ○ There are different types of these chains. Catalyst: PBG deaminase ○ Each of them are polypeptide chains because they are Product: Hydroxylmethylbilane made of a sequence of amino acids. 4 Hydroxylmethylbilane Catalyst: Uroporphyrinogen III synthase This transcript is strictly confidential and is intended for AVR 5TH FLOOR group members only; please don’t share or distribute! 2  HEMATOLOGY 1 | Lesson 4: Hemoglobin Globin Chains ○ Around the first three months of embryonic development. HEMOGLOBIN PAIRING Portland 2 Zeta / ζ (GamZet) 2 Gamma / γ Gower 1 2 Zeta / ζ (ZetEps) 2 Epsilon / ε Gower 2 2 Alpha / α (AlEps) 2 Epsilon / ε Globin Chains The genetic code of globin gives different types of globin A. FETAL HEMOGLOBIN chains. Hemoglobin F ○ Chromosomes 11 and 16 provide a unique DNA code Can be seen in newborns and adults. for each globin type ○ Found in minimal amounts in adults. 2 identical pairs. ○ Mainly found in newborns. These different types of globin chains are designated by 7 Formed during the second to the third trimester of fetal Greek letters. life, going up to birth. ○ Alpha-globin (α) & Zeta (ζ) has 141 amino acids. Presents itself during early embryogenesis. ○ Beta (β), Gamma (γ), and Delta (δ) all have 146 amino ○ Usually, it peaks during the 3rd trimester and begins to acids. decline just before birth. ○ Epsilon (ε) and Theta (θ) are still unknown. PROPORTION OF HEMOGLOBIN F Gamma A and Gamma G are differentiated by their 136th NEWBORN ADULT position of the amino acid. 20