Heme Synthesis and Breakdown Flashcards

(35 cards)

1
Q

What is Hb made of and what is at the center of each subunit?

A

It is made up of 2 alpha globins and 2 beta globins, each subunit is made up of 4 pyrrole rings (tetra pyyrole), called porphyrin ring. Iron Fe2+ (ferrous) is bound in the middle of each porphyrin ring

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2
Q

Where do the different stages of the biosynthesis of heme occur?

A

Phase one: Mito
Phase two: cytosol
Phase three: Mito

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3
Q

What is the first step in phase one of heme biosynthesis?

A

Glycine + Succinyl CoA forms Aminolevulinic acid (ALA) using ALA synthase and B6 (PLP)

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4
Q

What is the difference between ALASynthase 1 and ALASyntahse II?

A

1 is ubiquitous and 2 is only in BM and has an iron response element in mRNA

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5
Q

What happens once ALA is transported into the cytosol?

A

ALA dehydratase is used to form porphobilinogen (one pyyrole ring)

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6
Q

How is porphobilinogen made into hydroxymethylbilane?

A

4 of the porphobilinogens are by porpholinogen deaminase to form hydroxymehtylbilane (4pyyrole rings= to porphyrin ring)

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7
Q

How is hydroxymethylbilane made into Copro-porphyrinogenIII (2 steps)?

A

Using urophyrinogen synthase III to form Uro-porphyrinogen III and then uroporphyrinogen decarboxylase to form Copro-porphyrinogenIII

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8
Q

Once copro-porphyrinogen III is transported back into the mitochondria, how does it become Heme?

A

By using copro-oxidase which forms proto-porphyrinogen IX, combined with proto-porphyrinogen IX oxidase to form proto-porphyrin IX WHICH USES FERROCHELATASE TO FORM HEME

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9
Q

What does lead (from lead poisoning) inactivate, what is there a buildup of, and what disease does it cause?

A

Inactivates: ALA dehydratase and ferrochelatase
BuildUp: ALA & protoporphyrin IX
Anemia/ decrease energy production

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10
Q

What is porphyrias and what are the types?

A

Inherited metabolic disorders in heme synthesis . Two types: acute hepatic (liver), erythropoietic (bone marrow)

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11
Q

What is the defective enzyme and type of porphyria associated with acute intermittent porphyria?

A

E: porphoblinogen deaminase (PBG)
T: Hepatic porphyria

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12
Q

What is the defective enzyme and type of porphyria associated with Congenital erythropoietic porphyria?

A

E: uroporphyrinogen III synthase
T: Erythropoietic (BM)

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13
Q

What is the defective enzyme and type of porphyria associated with Porphyria cutanea tarda (PCT)?

A

E: Urophyrinogen decarboxylase
T: Hepatoerythropoietic (both liver / BM)

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14
Q

What is the defective enzyme and type of porphyria associated with Variegate porphyria (celebrity deaths)?

A

E: protoporphyrinogen IX oxidase
T: hepatic

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15
Q

What does congential erythropoietic porphyria cause a build up of and what is the product/side affect?

A

Causes a build up of uroporphyrinogen I and its oxidation product uroporphyrin I which is fluoroescent

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16
Q

What is the first step of heme degredation? What is used and produced?

A

Heme produces Biliverdin by heme oxidase. This reaction uses O2 and produces CO and Fe3+ (ferric)

17
Q

How is biliverdin made into Bilirubin?

A

Using biliverdin reductase and NADPH (removes double bond)

18
Q

What happens to billirubin once it is released into the bloodstream as free/indirect/unconjugated BR (insoluble)?

A

Binds to albumin and transported to liver where BR is conjugated with glucuronic acid (Bilirubin Diglucuronide), now called conjugated/direct BR.

19
Q

How is UDP glucuronate made and what catalyzes the reaction between UDP glucuronate and bilirubin?

A

Made by UPD Glucose (2NAD) and UDP glucose dehydrogenase, 2 UDP glucuronate are combined with bilirubin by Bilirubin UDP glucuronyltransferase, forming Bilirubin Diglucuronide

20
Q

When newly synthesized bilirubin diglucuronide is released, where does it go and when is it released?

A

conjugated bilirubin is sent to the gull pladder which is eventually released into the small intestine in response to food

21
Q

What happens to conjugated bilirubin in the intestine?

A

The diglucuronides are removed and bilirubin is reduced to urobilinogen

22
Q

What happens when the kidneys absorb urobilinogen?

A

it is made into urobilin (yellow) and excreted in urine

23
Q

What happens when urobilinogen undergoes further reduction in the intestine?

A

it is made into stercobilin (red-brown) and found in poop :)

24
Q

What causes jaundice and what are the different causes?

A

Hyperbilirubinemia, elevated levels of BR in blood

  1. pre-hepatic
  2. intra-hepatic
  3. post-hepatic
25
What causes pre-hepatic jaundice?
increased production of unconjugated BR which causes elevated blood levels of unconjugated/indirect/free BR
26
What causes intra-hepatic jaundice and some examples?
Impaired hepatic uptake (transporter), conjugation (transferase), or secretion of conjugated BR EX: Criggler-Najjar Syndrome (no enzyme transferase) Gilbert Syndrome
27
What are some findings indicative of intra-hepatic issues?
High serum ALT/AST, Conjugated BR in urine
28
What causes post-hepatic jaundice?
Cannot excrete billirubin, caused by decreased bile flow due to bile/gull stones
29
What are some findings indicative of post-hepatic issues?
elevated blood levels of conjugated BR, BR in urine (dark), pale stool, not yellow urine
30
What are neonatals deficient of and why (causes neonatal jaundice known as physiological jaundice)?
Deficient in UDP-GT (adds glucuronal to bilirubin) enzyme at birth-> fetal hemoglobin changes to HbA, cannot keep up with amount of bilirubin (NORMAL)
31
What is a treatment for neonatal jaundice (2)?
Blue fluorescent light (converts BR to more soluble isomers) | Tinmesoporphyrin (strong inihibtor of heme oxygenase) stops formation of BR
32
What is Crigler-Najjar Syndrome and what are the different types?
Syndrome resulting from deficiency of UDP-GT Type I: complete absence of gene : Severe Hyperbilirubinemia, ultimately need liver transplant Type II: Benign form, enzyme has 10% activity
33
What is Gilbert Syndrome?
Common/Benign, Results in 25% activity of UDP-GT enzyme | Serum BR increases when fasting, stressed, or with alcohol
34
What is hepatitis and what can it cause (regaurding BR as well)?
It is inflammation of the liver, leading to dysfunction. Caused by Hep A,B,C, alcoholism Increases levels of unconjugated and conjugated BR in blood, causing (intra-hepatic jaundice) yellow discoloration and dark urine
35
BRUISING breaks down from heme to iron
Hg--> Heme-Red Biliverdin-Green Bilirubin-Orange Hemosiderin (iron)- reddish brown