Chapter 10 Haemoglobin And Porphyrins Flashcards
Haemoglobin is a tetrameric allosteric protein . What does it mean??
A tetrameric allosteric protein refers to a protein that consists of four subunits and exhibits allosteric regulation.
Allosteric regulation means that the binding of a molecule to one site on the protein can affect the activity or function of another site on the protein.
Normal conc. of heme in males and females?
Molecular weight of hemoglobin and myoglobin?
In males:
14-16g/fdl
In females:
13-15g/dl
Molecular weight:
Hemoglobin-64,450
Myoglobin-17,000
Haem contain globin, the ____ part and heme the ____ part?
Globin - apoprotein
Heme - non-protein (prosthetic group)
Globin consists of _____ polypeptide chains?
In adult hemoglobin HbA1?
Number of amino acids?
4;
•2- alpha chains —141 amino acids
•2- beta chains—-146 amino acids
Total Amino acids in HbA1;
574
The 4 subunits of hemoglobin ar held together by?
Non-covalent interactions:
Hydrophobic
Ionic
Hydrogen bonds
Each subunit has a heme group
Structure of heme?
protoporhyrin IX
A Porphyrin molecule with iron at centre.
Protoporphyrin consists of;
4 pyrrole rings
To which, are attached:
1. 4 methyl
2. 2 proponyl
3. 2 vinyl groups
Heme is a common prosthetiv group present in cytochromes in certain enzymes eg?
1.Catalase
2.Tryptophan pyrolase
3.Chlorophyll (Mg2+)
About 80% of heme syntheis occurs in?
And the remaining in?
- Erythroid precursor cells in bone marrow
- Liver
What are erythroid cells?
Erythroid cells are the precursor cells that develop into erythrocytes, which are mature red blood cells.
Why mature erythrocytes don’t synthesize heme?
Because they dont have mitochondria or nucleus
Heme synthesis occurs in mitochondria or cytosol?
Partly in both:
1st step: ALA synthesis in —mitochondria
And last 3 steps: involving oxidase enzymes—–mitochondria
Rest in: cytosol
What are the 4 major most important events in heme synthesis?
- Porphobilinogen synthesis (PBG)
- PBG —–to—- uroporphyrinogen
- Uroporphyrinogen —-to— protoporphyrinogen IX
- Incorporation of iron
Pnemonic for steps of heme synthesis?
Some. Great.
Doctors
Palpate
Heart
Under
Cover
Produce
Pure
Heme
Succinyl coA + Glycine
|. (ALA synthase)
D-ALA
|. (ALA dehydratase)
|
Porphobilinogen
| (U synthase-I)
|
Hydroxymethylbilin
| (U synthase-III)
|
Uroporphyrinogen-III
|. (U decarboxylase)
|
Coroporphyrinogen-III
| (Co-oxidase)
|
Protoporhyrinogen-IX (III)
| (Pro- oxidase)
|
Protoporphyrin
| (ferrochelatase)
|
Heme
1.The coenzyme for ALA synthase in the 1st step for heme synthesis is?
- ALA synthase is inhibited by?
1.Pyridoxal phosphate (PLP)
- Lead
Deficiency of enzymes ALA synthase and ALA dehydrogenase lead to?
Anemia
1.Deficiency of enzyme uroporphyrinogen-I synthase leads to?
- Treated by?
- Caution?
1.Acute intermittent porphyria
- Administration of hematin (inhibits enzyme ALA synthase and the accumulation of PBG)
- Avoid drugs (e.g, barbiturates) that induce synthesis of **cytochrome P450)—– due to increased activity of ALA synthase —— accumulation of PBG +ALA
Congenital eryhthropoeitic porphyria is caused due to deficiency of which enzyme?
Uroporphyrinogen-III synthase
Deficiency of enzyme Uroporphyrinogen decarboxylase leads to?
Porphyria Cutanea Tarda
Which is the most common porphyria?
Porphyria cutanea tarda
Deficiency of enzyme coproporphyrinogen oxidase leads to?
Heridity coproporphyria
Deficiency of protoporphyrinogen oxidase leads to?
Variegate porphyria
Deficiency of ferrochelatase leads to?
Protoporhyria also known as erythropoietic protoporphyria
What is porphyria?
Porphyrias are a group of rare genetic disorders that affect the production of heme, a component of hemoglobin.
-enzymes that code for heme synthesis are affected
- characterized by increased exctertion of porphyrins or porphyrin precusors
. It can cause a variety of symptoms, including ;
•abdominal pain,
•skin sensitivity to sunlight,
•neurological issues,
• psychiatric symptoms.
Porphyrias are either inherited or acquired, classified into?
2 categories;
1.Erythropoetic
Enzyme deficiency in eryhthrocytes
2.Hepatic
Enzyme defect in liver