Heme Derivatives Flashcards
Is Heme a protein?
Heme is not a protein; it is a prosthetic group found in hemoglobin, myoglobin, chlorophyll, cytochromes, and several other enzymes
Where is Heme most concentrated in?
Most concentrated in RBCs and Liver cells
Porphyrins
Intermediates of the enzymatic pathway of heme synthesis
Elevated porphyrins (porphyria) are either _________ or ________
Erythropoietic or hepatic
Synthesis of heme is regulated by _______ feedback of heme (something happens to throw the body out of regulation, your body tries to counteract it to get it back to “balance”…….. Ex: Low on heme, sends biosignals to make more RBCs to make more heme)
Negative
Porphyrias
Are rare inherited metabolic disorders caused by loss/gain of function enzymes responsible for heme biosynthesis
Porphyrias may also be classified based on their associated symptoms as acute or cutaneous (non-acute).
Can also be caused by liver diseases or and heavy metal poisoning as well
Cutaneous (non-acute) Porphyrias:
- Chronic conditions
- Photosensitivity
- Blistering lesions
Testing used to monitor and diagnose Porphyrias
Genetic assays
Function/quantitative assays for enzymes responsible for heme synthesis
Identify/quantify porphyrins and other precursor compounds
(Must be protected from light to prevent degradation)
Urine Porphyrin Testing
Stable for 48 hours refrigerated and several weeks frozen
Dilute samples (creatinine <25 mg/dL) inadequate for testing
Porphyrin in urine causes it to have a Port wine color
Stool Porphyrin Testing
Must be stored frozen
Blood Porphyrin testing
EDTA whole blood samples
Stored in the dark refrigerated
What is Hemoglobin?
Is classified as a transport protein.
Its role is to transport oxygen from the lungs to the tissues, and transport carbon dioxide back to the lungs.
Heme synthesis occurs in plasma and mitochondria
The steps catalyzed by ALA dehydratase and ferrochelatase are inhibited by LEAD (how heavy metals inhibit the synthesis of heme)
Hemoglobin synthesis occurs in the immature RBCs located in the bone marrow
2 α-like chains and 2 β-like chains that surround a heme molecule
Synthesis of hemoglobin
Synthesized in RBCs located in bone marrow
Iron is inserted into heme to help bind Oxygen
After RBC lysis hemoglobin is transported to the liver to be recycled
- Iron is stored (ferritin)
- Globin chains broken down into amino acids
- Heme converted to bilirubin and urobilinogen
Testing of hemoglobin
Hemoglobin concentration is part of CBC
Sickle Cell Anemia
HbA mutated to HbS
Thalassemia
Mutation reduce the amounts of normal hemoglobin produced
Hemoglobinopathies
Mutations globin chain that produce structurally different hemoglobin decreasing RBC survival
How can Hemoglobinopathies be evaluated?
Evaluated via electrophoresis
What is myoglobin?
Myoglobin is the primary oxygen-carrying protein found in striated skeletal and cardiac muscle, accounting for approximately 2% of total muscle protein.
When striated/cardiac muscle is damaged myoglobin is released
Is a nephrotoxin, severe muscle damage (muscle torn or separated from tendon) can cause harm to the kidneys
Heart attack, muscle injury
Liver
Liver is an extremely vascular organ that receives its blood supply from two major sources: the hepatic artery and the portal vein.
Excretory and Secretory Functions (Liver)
Processing and excretion of endogenous and exogenous substances into the bile or urine such as the major heme waste product bilirubin
The liver is the only organ that has the capacity to rid the body of heme waste products.
Unconjugated bilirubin
(indirect and has not had glucuronic acid attached to bilirubin) is insoluble in water and cannot be removed from the body until it has been conjugated by the liver.
Conjugated bilirubin
(glucuronic acid attached to bilirubin) is water soluble and can be secreted from the hepatocyte into the bile canaliculi.
_______ mg of bilirubin is produced per day
200-300 mg
Key Points of Bilirubin Metabolism
After RBC destruction hemoglobin is broken down into heme and globin
Heme is further broken down into unconjugated bilirubin to be transferred to the liver by albumin
In the liver converts unconjugated bilirubin to conjugated bilirubin
In the intestines conjugated bilirubin is converted to urobilinogen
50-250 mg of urobilinogen is excreted in feces per day
1-4 mg of urobilinogen is excreted in the urine per day
Metabolism and how they can process carbs
Second major function of the liver is the metabolic processes.
Metabolism of carbohydrates is one of the most important functions of the liver.
Can process them in one of three ways:
(1) use the glucose for its own cellular energy requirements
(2) circulate the glucose for use at the peripheral tissues
(3) store glucose as glycogen (principal storage form of glucose) within the liver itself or within other tissues
Is responsible for metabolizing both lipids and the lipoproteins and is responsible for gathering free fatty acids from the diet, and those produced by the liver itself, and breaking them down to produce acetyl-CoA
Almost all proteins are synthesized by the liver except for the immunoglobulins (produced by WBCs) and adult hemoglobin (produced mainly in the bone marrow).
Detoxification and Drug Metabolism
Serves as a gatekeeper between substances absorbed by the gastrointestinal tract and those released into systemic circulation
System is responsible for the detoxification of many drugs through oxidation, reduction, hydrolysis, hydroxylation, carboxylation, and demethylation
To get rid of drugs, your body will have to get rid of it by using the liver. Abusing drugs impacts your liver.