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43 Cards in this Set
- Front
- Back
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Major adult form of Hemoglobin
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Two α and Two Beta chains called HbA or HbA1
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What hemoglobobin predominates in the fetus?
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HbF
Has higher affinty for O2 to take Maternal O2 |
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How many types of globin exist?
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6
2 Alpha 4 Beta |
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Sickle Cell Disease
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Mutation in Beta Globin Chain
Goal of therapy is to increase the number of F cells |
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What is Heme made of?
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Protoporphyrin IX and 1 ferrous iron (Fe2+) in the center
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Proximal Histadine
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The bond formed between the Fe2+ of heme and a histidine AA in the F helix
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Distal Histidine
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On the E helix is in close proximity and helps stabilize
Helps prevent oxidation of Fe2+ to Fe3+ (doesnt bind O2) And reduces Hb affintiy for CO |
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Where do the first step and last 3 steps of heme production take place?
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In the mitochondira
Other steps in the cytosol |
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Where is the organic portion of Heme derived from?
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Glycine and Succinyl CoA(which is probably why in mitochondria b/c this is where Succinyk CoA is)
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Ferrochetalase
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Binds the Fe2+ and Protoporphyen IX to Heme
Inhibited by Lead |
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ALA Synthase
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Catalyze first rxn
Inhibited by Heme Requires B6 as cofactor Rate-limiting |
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ALA Dehydratase
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Involved in rxn 2 forms first of chiral rings
Inhibited by lead |
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ALAS1
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Expressed in Liver
Constitutive Regulated by negative feedback of Heme Inhibits transcription Increases mRNA degradation Blocks post-translational translocation Induced by hormones Inhibited by glucose Similar to P450 does not involve O2 transport |
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ALAS2
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Erythroid cells in bone marrow
Makes heme for Hb so its response is much slower Regulated in response to iron Iron response 5' UTR Indirectely regulate acquistion of Fe from its transport Transcription is regulated by an erythoid specific promotor and same factors that regulate globin synthesis |
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Erythropoietin
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Induces transcription of ALAS2
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What is regulated in coordination of Heme synthesis
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The availability of apoproteins
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Lead poisoning
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Inhibits ALA dehydratase and ferrocheltalase
Symptoms are age and dose dependent Anemia Neurological problems |
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Porphyrias
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Rare, can be congenital
Most are dominitly inherited Except Erythropoietic Most Effect Liver Except Hereditary Coproporphyria & Erythropoietic (Marrow) |
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Congenital Erythropoitic Porphyria
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Extra hair growing on skin
Gum line recedes Red Urine Garlic Induced May give rise to werewolves and Vampires |
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T form
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Deoxy form
Two αβ dimers held together by ionic and hydrogen bonds that constrain the movement |
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R form
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Oxygenated
Binding of O2 ruptures some of the bonds between the two dimers Seen in the lungs |
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2,3 BPG
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Allosteric Inhibitor
Creates more ionic bonds in T Presence signigicantly reduces the affinity of Hb for O2 Shifts the O2 curve to the right Has weak ability to bind HbF |
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Bohr Effect
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Allosteric Inhibitor
When O2 binds it releases H+ In tissue the H+ conc. is higher then lungs as the conc. raises the affinty for O2 decreases Rxn goes to the Left and O2 saturation curve to the Right |
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Carbonic Anhydrase (CO2)
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Converts CO2 to bicarbonate
Helps buffer blood When CO2 come into the Tissues its aced on by this enyzme it breaks down to bicarb and H+ which helps release O2 |
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Carbamino-Hemoglobin
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Transports CO2 to the lungs on Hb which also produces H+ so binding of CO2 promotes the release of O2 form Hb
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Feedback mechanism of Bohr Effect
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Helps get rid of metabolic waste and deliver O2
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β Thalassemia
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Deficiency of β chains
Excess α chains precipitate causeing RBC to be destroyed resuling in Anemia |
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α Thalassemia
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Deficiency of α chains
Sevirity depends on how many of the 4 chains affected lack of them all will fatal before birth |
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Sickle Cell
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Point mutation in Beta globin
Hb S synthesized normal amt. O2 affinity normal Reduced solubility |
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Methemoglobinemia
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Chocolate blood
Treated with methylene blue except for pts. with G6PD deficiency |
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Degradation heme
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Begins in macrophages of the RES with removal of globin chains and conversion of heme to bilirubin
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What is bilirubin conjugated with in liver?
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After being transported by albumin to liver it is conjugated with glucuronic acid to make it more soluble and excreted in bile
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What de-conjugates bilirubine?
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After being excreted into the intestine with bile it is de-conjugated by bacteria and converted to Urobilinogens
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Urobilinogen
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Some go to kidney converted to Urobulin (yellow)
Most become Stercobilin (brown) |
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Prehepatic Jaundice
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Increase UB
Exceeds capacity of liver to conjugate it No BR in urine Caused by: HEMOLYSIS, Sickle cell in crisis and malaria |
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Intrahepatic Jaundice
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Problem is in hepatocytes
Any of the 3 steps Harder diagnosis b/c you see both UB and CB Conjugated BR in Urine |
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Post Hepatic Jaundice
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Problem is getting CB out to intestines
Dark Urine No CB excreted in gut so get PALE stool |
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Neonatal Jaundice
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Increased levels of UB in premature infants b/c enzyme is not fully active until about 4 weeks after birth
Treated with blue fluorescent light |
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Bilirubin Glucuronyl Transferase
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Conjugates Bilirubin
Expression developmentally regulated Reaches adult levels at 4 months |
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Crigler-Najjar Syndrome
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Genetic defficiency of Bilirubin Glucuronyl Transferase
Type 1: Severe Type 2: Less |
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Gilbert Syndrome
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Benign, quite common
Midly elevated indirect bilirubin Causes a decreased expression |
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Haptoglobin
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Prevents loss of iron
Binds to dimers producing a complex to large to be filtered Prevetns tissue damage due to build up of Fe Deliver Hb to liver Acute phase reactant levels may increase during inflammation/infection |
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Hemopexin
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?
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