ENZYMES, GROWTH FACTORS, PROTEINS, AND RECEPTORS

Hemoglobin

Protein of a red blood cell (RBC) that contains iron and is responsible for delivery of oxygen to the tissues

Spectrin

Protein attached to the lipid bilayer of the RBC membrane, commonly affected by pathogenic mutations in Hereditary Spherocytosis (HS)

Ankyrin

Protein attached to the lipid bilayer of the RBC membrane, commonly affected by pathogenic mutations in Hereditary Spherocytosis (HS)

Band 3

Protein attached to the lipid bilayer of the RBC membrane, commonly affected by pathogenic mutations in Hereditary Spherocytosis (HS)

Band 42

Protein attached to the lipid bilayer of the RBC membrane, commonly affected by pathogenic mutations in Hereditary Spherocytosis (HS)

alpha-globin chains and beta-globin chains

Globin chains that compose Normal hemoglobin (HbA)

Heme group

Ring-like group containing an iron atom in hemoglobin

HbA or Hemoglobin adult

The main form of hemoglobin found in an adult

HbS or Abnormal hemoglobin

Hemoglobin form that undergoes polymerization when deoxygenated, resulting in the sickling of red blood cells (RBCs)

HbA2

Hemoglobin form composed of 2 alpha and 2 delta chains

HbF or Fetal hemoglobin

A normal type of Hb composed of 2 alpha and 2 gamma-globin chains, expressed until around 6 months of age

HbF or Fetal hemoglobin

Hemoglobin form whose gamma globin chains allow oxygen to bind stronger so that the developing fetus can retrieve oxygen from the mother’s bloodstream

Hemoglobin degradation products

Accumulate in hemolytic anemias, created as part of the process of red cell hemolysis

Chemokines

Chemical mediators released in the proinflammatory environment of sickle cell anemia that change red cell morphology

Adhesion molecules

Released in the proinflammatory environment of sickle cell anemia that change red cell morphology

beta-globin gene

Gene where a missense mutation occurs, leading to the replacement of glutamate to valine, thus causing Sickle Cell Disease

beta-globin chains (unpaired)

Excess chains that aggregate and form precipitates that damage red cell membranes in beta-thalassemia

Erythroferrone

Hormone secreted by red cell precursors in beta-thalassemia that inhibits the production of hepcidin

Hepcidin

A negative regulator of iron uptake in the small intestine

Hepcidin

The master regulator of the systemic iron metabolism that controls the release of iron from duodenal enterocytes and macrophages into the circulation

HbH

Excess beta-globin chains that bind to each other when 3 alpha-globin genes are deleted in alpha-thalassemia

HbH

Protein that has an extremely high affinity for O2, leading to tissue hypoxia disproportionate to the level of hemoglobin

HbH

Protein prone to oxidation, causing it to precipitate and form intracellular inclusions that promote phagocytosis and splenic sequestration

beta and gamma chains

Hemoglobin chains that are more soluble than free alpha chains

Zeta chains

Chains produced in Hemoglobin Bart's Hydrops Fetalis that can bind to gamma chains, making a somewhat functional tetramer that enables the fetus to survive the early trimester

Phosphatidylinositol glycan complementation group A gene (PIGA)

The gene that, when genetically defective, causes Paroxysmal Nocturnal Hemoglobinuria (PNH)

Enzyme (encoded by PIGA)

Enzyme essential for synthesis of certain membrane-associated complement regulatory proteins

Membrane-associated complement regulatory proteins

Act as a shield around red cells that can fend off the C5B to C9 membrane attack complex

CD59 and CD55

Proteins whose absence is demonstrated by flow cytometry to confirm the diagnosis of PNH

Haptoglobin

Protein that comes from the liver and clears out free hemoglobin

IgG and IgA

Causative antibodies in Warm Antibody Type immunohemolytic anemia that bind stably to red cells at 37 degrees Celsius

IgM

Antibody that binds to the red cells on low temperatures (around 0-4 degrees Celsius) in Cold Agglutinin Type immunohemolytic anemia

IgG autoantibodies

Antibody associated with Cold Hemolysin Type immunohemolytic anemia that binds to the P blood group antigen on the red cell surface

Glycoprotein IIb/IIIa or Ib-IX

Platelet transmembrane receptors against which autoantibodies are produced in chronic Immune Thrombocytopenic Purpura (ITP)

Erythropoietin (EPO)

Hormone produced by the kidney that stimulates the production of red blood cells

Erythropoietin (EPO)

Substance whose elevated level in hemolytic anemias causes a compensatory increase in erythropoiesis

Glucose-6-Phosphate Dehydrogenase (G6PD)

Enzyme that reduces NADP to NADPH while oxidizing glucose-6-phosphate

NADPH

Molecule generated by G6PD which oxidizes glutathione to its reduced form, neutralizing superoxides to water

Reduced glutathione

Molecule that neutralizes superoxides to water, oxidized by NADPH

Duodenal cytochrome b (d-cyt-b) protein

Ferrireductase enzyme localized on the brush border membrane of the enterocytes

Duodenal cytochrome b (d-cyt-b) protein

Enzyme responsible for the reduction of ferric ion (Fe3+) to ferrous ion (Fe2+)

Transferrin

Protein that iron circulates around the body bound to

Hemosiderin and ferritin

Proteins representing the storage pool of iron

Ferritin

Protein that measures total body iron storage

Methionine Synthase

Enzyme for which Vitamin B12 (Cobalamin) acts as a cofactor

Methionine Synthase

Enzyme that catalyzes the conversion of homocysteine to the essential amino acid methionine

L-methylmalonyl-CoA Mutase

Enzyme for which Vitamin B12 (Cobalamin) acts as a cofactor

L-methylmalonyl-CoA Mutase

Enzyme that converts L-methylmalonyl-CoA to succinyl-CoA in the Krebs cycle

Methylcobalamin

Serves as an essential cofactor in the conversion of homocysteine to methionine

N5-methyltetrahydrofolic acid (N5-methyl FH4)

The principal form of folic acid in plasma

N5-methyltetrahydrofolic acid (N5-methyl FH4)

Converted to tetrahydrofolic acid (FH4) during the methionine synthase reaction

Tetrahydrofolic acid (FH4)

Crucial building block for DNA

Haptocorrin (previously transcobalamin 1)

A cobalamin-binding protein found in the saliva

Intrinsic factor

A transport and delivery binding protein secreted by the stomach’s parietal cells, which B12 combines with in the duodenum

Intrinsic factor

Protein whose deficiency causes Pernicious Anemia

Transcobalamin II

The major carrier protein that Vitamin B12 associates with once in ileal cells, delivering B12 to the liver and other cells

Parietal cells

Cells in the stomach (oxyntic mucosa) that secrete intrinsic factor

Dihydrofolate reductase

Enzyme inhibited by methotrexate, causing a deficiency of tetrahydrofolic acid (FH4)

IL-6 (Interleukin-6)

Inflammatory mediator that causes increased hepcidin production by the liver (due to chronic conditions)

Ferroportin

Receptor that Hepcidin binds to, resulting in decreased intestinal iron absorption and decreased iron release from liver and macrophages

Cytokines

Inflammatory mediators that suppress erythroid precursor proliferation and inhibit kidney erythropoietin release in anemia of chronic inflammation

INF-gamma and TNF

Cytokines that suppress and kill the host’s hematopoietic progenitors in immune-mediated aplastic anemia

Globoside

Antigen found exclusively on RBCs that acts as a receptor for the Parvovirus B19

Telomerase

Protein required for cellular immortality and limitless replication, whose deficits result in premature hematopoietic stem cell exhaustion

Factor 1 (Fibrinogen)

Clotting factor whose deficiency is detected by Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT)

Factor 2 (Prothrombin)

Clotting factor whose deficiency is detected by Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT)

Factor 2a (Thrombin)

Protein that catalyzes the conversion of fibrinogen into fibrin

Factor 5

Clotting factor whose deficiency is detected by Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT)

Factor 7

Clotting factor whose deficiency is detected by Prothrombin Time (PT)

Factor 8

Clotting factor whose deficiency is detected by activated Partial Thromboplastin Time (aPTT)

Factor 8

Essential cofactor of Factor 9, which converts Factor 10 to Factor 10a

Factor 9

Clotting factor whose deficiency is detected by activated Partial Thromboplastin Time (aPTT)

Factor 10

Clotting factor whose deficiency is detected by Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT)

Factor 11

Clotting factor whose deficiency is detected by activated Partial Thromboplastin Time (aPTT)

Factor 12

Clotting factor whose deficiency is detected by activated Partial Thromboplastin Time (aPTT)

Factor 13

Clotting factor that helps form a stable mesh of fibrin in secondary hemostasis

von Willebrand Factor (vWF)

Protein synthesized in endothelial cells and megakaryocytes that binds to and stabilizes Factor 8 in the circulation

von Willebrand Factor (vWF)

Protein that promotes the adhesion of platelets to the subendothelial matrix, primarily via the glycoprotein 1b (Gp1b) platelet receptor

Glycoprotein 2b-3a (alpha 2b beta 3)

Platelet integrin whose deficiency or dysfunction causes Glanzmann Thrombasthenia

Glycoprotein 2b-3a (alpha 2b beta 3)

Integrin that participates in "bridge formation" between platelets by binding fibrinogen

Glycoprotein 1b-9

Glycoprotein complex whose deficiency leads to Bernard-Soulier Syndrome

Glycoprotein 1b-9

A receptor for vWF that is essential for normal platelet adhesion to the subendothelial extracellular matrix

ADAMTS13

Plasma enzyme that degrades very high-molecular-weight multimers of von Willebrand factor (vWF)

ADAMTS13

Enzyme whose deficiency causes Thrombotic Thrombocytopenic Purpura (TTP)

Shiga-like toxin

Toxin elaborated by E coli strain O157:H7 that incites platelet activation and aggregation in typical Hemolytic Uremic Syndrome (HUS)

Complement Factor H, Membrane Cofactor Protein (CD46), and Factor 1 (Complement)

Proteins whose defects are associated with Atypical HUS and that prevent excessive activation of the alternative complement pathway

Cyclooxygenase

Enzyme required for the synthesis of thromboxane A2 and prostaglandins

Aspirin

A potent, irreversible inhibitor of cyclooxygenase

Thromboxane A2 and Prostaglandins

Mediators that play important roles in platelet aggregation and subsequent release reactions

ADP (Adenosine diphosphate) and Serotonin

Factors released by activated platelets to recruit other platelets for aggregation

Protein C and Protein S Systems

Natural anticoagulants that inhibit Factor 5 and Factor 8

Antithrombin 3

Natural anticoagulant that inhibits Thrombin and Factor 10

Tissue Factor Pathway Inhibitor (TFPI)

Natural anticoagulant that inhibits Tissue Factor and Factor 7

Plasmin

Enzyme that breaks down stable fibrin

CD4 and CXCR4

The receptor and co-receptor for the retrovirus, HIV, found on megakaryocytes

JAK2 mutation

Mutation that results in dysregulated production of erythrocytes, platelets, and myelocytes, causing Primary Absolute Polycythemia

JAK2 mutations

Activating point mutations associated with Polycythemia Vera (>95% of cases)

JAK2 mutations

Activating point mutations seen in 50-60% of Essential Thrombocytosis cases

JAK2 mutations

Activating point mutations seen in 50-60% of Primary Myelofibrosis cases

BCR-ABL fusion gene

Gene that distinguishes Chronic Myeloid Leukemia (CML) and causes constitutive ABL kinase activation