Heme Synthesis and Breakdown Flashcards Preview

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Flashcards in Heme Synthesis and Breakdown Deck (13):
1

Structure of Heme

Heterocyclic porphyrin ring with iron present in center

Have 4 5-membered rings containing Nitrogen connected by single carbon bridges
Iron present in ferrous state (Fe2+)
Oxidation to ferric state (Fe3+) inactivates hemoglobin (methemoglobin)

Present in Hb, myoglobin, cytochromes

2

Structure of Hemoglobin

Contains 4 globular protein subunits
Each bound to an iron containing heme

3

ALA Synthase

Heme synthesis
Glycine + Succinyl CoA --> Delta aminolevulinic acid

Needs Vit B6 (Pyridoxal phosphate)
2 Isoforms:
1) ALAS I (ubiquitous) inhibited by heme and hemin
2) ALAS II (only in erythroid cells of BM) has iron response element in mRNA
-Presence of iron increases its transcription and translation

4

Porphyrias

Inherited metabolic disorders
Greek for "Purple pigment"
Caused by defects in heme synthesis

Types depend on enzyme defect
1) Acute hepatic - neurological symptoms
2) Erythropoeitic - skin, photosensitivity

5

Acute intermittent porphyria

Defective enzyme: PBG deaminase (in liver)
Hepatic porphyria

Rxn: PBG --> Hydroxymethylbilane

6

Congenital erythropoietic porphyria

Defective enzyme: Uropophyrinogen III cosynthase (in erythrocytes)
Erythropoietic porphyria

Rxn: Hydroxymethylbilane --> Urophorphyrinogen III

Uroporphyrinogen III --> Uroporphyrinogen I accumulates
Red color in urine
Red flourescence in teeth
Destruction of RBCs
Skin photosensitivity

7

Porphyria cutanea tarda

Defective enzyme: Uroporphyrinogen decarboxylase
Hepatoerythropoietic prophyria
**Most common porphyria in US

Rxn: Uroporphyrinogen III --> Coproporphyrinogen III

8

Variegate porphyria

Defective enzyme: Protoporphyrinogen IX oxidase
Hepatic porphyria

Rxn: Protoporphyrinogen IX --> Protoporphyrin IX

King George III
Intermittent abdominal pain
Delirium
Hallucinations
Convulsions
Medicines contained arsenic

9

Crigler-Najjar Syndrome type I

Deficiency of UDP-GT enzyme
-Complete absence of gene

BR accumulates in brain of babies --> encephalopathy (kernicturus) & brain damage

Therapy:
Blood transfusions
Phototherapy
Heme Oxygenase inhibitors
Oral calcium phosphate and carbonate (form complexes with bilirubin in gut)
Liver transplant before brain damage occurs and before phototherapy becomes ineffective

10

Crigler-Najjar Syndrome Type II

Mutation in UDP-GT
Benign form
Enzyme has less activity (10%)

11

Gilbert Syndrome

Common benign disorder
Reduced activity of UDP-GT (25% activity)
Serum BR <6 mg/dL but may increase with fasting, stress, or alcohol consumption

12

Hepatitis

Inflammation of liver --> liver dysfunction
Causes- Viral infections (Hep A, B, C), alcoholic cirrhosis, liver cancer

Increased lvls of unconjugated and conjugated BR in blood
BR accumulates in skin and sclera of the eyes --> yellow discoloration
Dark tea colored urine

13

Color changes in bruises

Hemoglobin- reddish purple
Heme- red
Biliverdin - green
Bilirubin - reddish orange
Hemosiderin (iron) - reddish brown