liveonearth (liveonearth) wrote,

Biochemistry: Heme and Iron Metabolism

24. Place the following heme degradation products into the correct production sequence:
biliverdin --> bilirubin --> bilirubin diglucuronide -->urobilinogen --> stercobilin

25. Heme degradation sites: Old RBC's lysed in spleen (major) and liver (minor). What is the control point in heme degradation? The conjugation and excretion of bilirubin in bile.

26. Characterize the causes of jaundice (by location and metabolic action).
Prehepatic aka hemolytic, anything that destroys RBC's in high numbers, ex: sickle cell anemia
Hepatic aka hepatocellular, liver conditions that interfere w/ bilirubin uptake or conjugation ex: cirrhosis
Posthepatic aka obstructive, something stops the bile, duct problem

27. How does phototherapy work for jaundice in newborns? Glucuronic acid and bilirubin are conjugated in liver to make it water soluble, Newborns with jaundice lack enzyme: bilirubin glucuronyl transferase, give them blue flourescent light, the light changes the intermediates to more water soluble forms.

Why is glucuronic acid attached to bilirubin?
The liver "conjugates" bilirubin with glucaronic acid to make bilirubin diglucuronide which is water soluble, and is secreted in the bile.

Bilirubin is the yellow breakdown product of normal heme catabolism, formed by failing red blood cells. Bilirubin is excreted in bile, and its levels are elevated in certain diseases. It is responsible for the yellow colour of bruises and the brown colour of feces. Bilirubin reduction in the gut leads to a product called urobilinogen which is then oxidized to urobilin which is excreted in the urine.

28. What are the intracellular iron storage proteins? hemosiderins and ferritin
Circulating iron-transfer protein? transferrin

Discuss the general scheme of iron metabolism. Iron is taken in with diet, absorbed better with vit C. Synthesis of hemes is in bone and liver.

29. What are the starting materials for heme synthesis? Succinyl Co A and glycine.

What is the rate limiting enzyme and intermediate formed from that step? gamma-ALA synthase, aka gamma-aminolevulinic acid synthase, makes gamma-aminolevulinic acid

What vitamin is required for heme biosynthesis? pyridoxal phosphate = PLP = active B6

What are the regulators of heme synthesis?
Level of heme in cell controls enzyme activity and transcription of gamma-aminolevulinate gene

30. What prominent proteins contain heme as a cofactor? hemoglobin, cytochromes, peroxidases and catalase

31. Why does metabolism of some lipid-soluble drugs promote heme synthesis? The detoxification of lipid soluble drugs in the liver often happens via hydroxylation using CYP450's, which are inducible. Your liver uses up all the available heme making CYP's so it upregulates ALA-synthase activity to make more heme. So when you have these drugs in your system, your body ramps up production of certain enyzmes, some of which require heme to function, so heme production is also increased as a result of the production cascade.

--diverse biological functions including the transportation of diatomic gases, chemical catalysis, diatomic gas detection, and electron transfer
--source or sink of electrons during electron transfer or redox chemistry
--electron source in peroxidase reactions
--gas binds to the heme iron in transportation or detection of diatomic gases
--gas binding to heme iron induces conformational changes in the surrounding protein
--original evolutionary function of hemoproteins may have been electron transfer in primitive sulfur-based photosynthesis pathways in ancestral cyanobacteria (before the appearance of molecular oxygen)
--the ability of hemoglobin to effectively deliver oxygen to tissues is due to specific amino acid residues located near the heme molecule. Hemoglobin binds oxygen in the pulmonary vasculature, where the pH is high and the pCO2 is low, and releases it in the tissues, where the situations are reversed. This phenomenon is known as the Bohr effect. The molecular mechanism behind this effect is the steric organization of the globin chain; a histidine residue, located adjacent to the heme group, becomes positively charged under acid circumstances, sterically releasing oxygen from the heme group.

The pathway is initiated by the synthesis of D-Aminolevulinic acid (dALA or δALA) from the amino acid glycine and succinyl-CoA from the citric acid cycle (Krebs cycle). The rate-limiting enzyme responsible for this reaction, ALA synthase, is strictly regulated by intracellular iron levels and heme concentration. A low-iron level, e.g., in iron deficiency, leads to decreased porphyrin synthesis, which prevents accumulation of the toxic intermediates. This mechanism is of therapeutic importance: infusion of heme arginate of hematin can abort attacks of porphyria in patients with an inborn error of metabolism of this process, by reducing transcription of ALA synthase.
The organs mainly involved in heme synthesis are the liver and the bone marrow, although every cell requires heme to function properly. Heme is seen as an intermediate molecule in catabolism of haemoglobin in the process of bilirubin metabolism.
Tags: biochemistry, blood, detox, elimination, hemoglobin, iron, liver, protein

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