Question

Can you please explain in detail heme degradation and explain in detail DNA repair mechanisms. It is really important to me. I will be forever grateful. And if I may ask you one thing if you copy from the internet please put the citations, or links. Thank you in advance!!!

Answer 1

Heme degradation- it occurs in following steps -

A) Generation of Bilirubin
------Heme is catalyzed and converted in to bilirubin. As Bilirubin has no function so it is excreted through bile. Catabolism of heme occurs in Reticulo endothelial system of liver spleen and in bone marrow. RBC after completion of their life cycle enters in to RE system and metabolized there. 300mg of bilirubin formed each day in our body, in this 80 % of total contributed by old RBC and 10% from heme containg proteins and 10% from ineffective erythropoiesis.

----From haemoglobin, heme and globin chains are seprated. Globin is reused and heme is catabloized.

-----Heme is degraded primarily by a microsomal enzyme heme oxygenase. oxygenase enzyme cleavage
the alpha methenyl bridge (present in between pyrol rings I and II) . And this lead to formation of linear tetrapyrrole ring billiverdin ( green colour) .later this billverdin is reduced by billiverdin reductase and converted in ti bilirubin. Which is excreted in to bile .
-----The Fe++ liberated during heme degradation is oxidized to Fe+++ and taken up by transferrin.

B) transport to liver-

bilirubin formed in RE system is transferred to liver. As this bilirubin in hydrophobic in nature . So protein albumin plays an important role in tranport of bilirubin to liver.

C) conjugation in liver -

Once albumin - bilirubin complex reached to liver , it is uptake by carrier mediated active process. In side liver bilirubin is conjugated by enzyme bilirubin glucronide transferase and convert insoluble bilirubin to
water-soluble.

D) excretion of bilirubin in bile-

This water soluble conjugated bilirubin enters in to bile duct along with bile by a active process . This is rate limiting step and MOAT carrier protein involve in transport of bilirubin.

E) fate of conjugated bilirubin in to intestine. -

-- conjugated bilirubin reaches the intestine
through the bile. In the intestine, intestinal bacteria are present which deconjugate the conjugated bilirubin.  

--This free bilirubin is later reduced to a colorless tetrapyrrole urobilinogen and later further reduction leads to generation of stercobilinogen. The SBG is mostly excreted through feces (250–300 mg/day)

F) final excretion in to faeces and urine.

During enterohepatic circulation, a small amount of free bilirubin enter in to blood which is excreted through urine.

Final excretion occur in form of urobilin-- in urine

Stercobillin-- in faeces.

For better understanding, I have attached image which explain all these .

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i have solved only one question because these two questions are too lengthy. Please post second question separately.