5-14 GOUELI Heme Metabolism Flashcards

1
Q

What is the rate limiting step in the synthesis of heme?

A

Glycine + Succinyl-CoA –> δ-ALA (aminolevulinic acid)

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2
Q

How is δ-ALA synthase activity regulated?

A

Negative feedback from Heme

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3
Q

What is the significance of vitamin B6 in heme synthesis?

A

It’s a cofactor for δ-ALA synthase

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4
Q

What can a vitamin B6 deficiency cause?

A

↓B6 –>↓Hb synthesis –> microcytic, hypochromic (low color) anemia

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5
Q

What is one concern with Isoniazid?

A

Isoniazid, which is Tx for TB, can –> B6 deficiency

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6
Q

What’s the site of lead toxicity in the heme synthesis pathway?

A

δ-ALA dehydratase, and ferrochelatase

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7
Q

What can lead toxicity lead to?

A

Microcytic anemia

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8
Q

What does heme positively increase production of?

A

Globin, to make hemoglobin

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9
Q

What happens to heme after RBCs die?

A

It is degraded to bilirubin

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10
Q

Where does the breakdown of heme to bilirubin occur?

A

In the RES (Reticuloendothelial system, ie spleen, macrophages, etc)

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11
Q

What happens to bilirubin in the liver?

A

It is conjugated

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12
Q

What do we mean when we say bilirubin is conjugated?

A

You’re adding UDP-glucouronate to make it more water soluble

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13
Q

What is the difference btwn direct and indirect bilirubin?

A

Direct is conjugated. Indirect is unconjugated.

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14
Q

What is the significance of direct vs indirect bilirubin?

A

If patient has jaundice (which is due to build-up of bilirubin), type of bilirubin (direct vs indirect) can help us figure out where damage is occurring

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15
Q

If patient has intravascular hemolysis (like seen in G6PD deficiency), what form will the bilirubin in her system be in?

A

Unconjugated (indirect) form b/c it hasn’t passed through liver yet

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16
Q

If patient has obstruction of biliary system, what form will the bilirubin in his system be in?

A

Conjugated bilirubin (direct) b/c it HAS passed through liver

17
Q

Define porphyria

A

A genetic deficiency in one of the enzymatic steps of the heme synthesis pathway –> disease b/c toxic accumulation of enzyme precursor

18
Q

How can you detect a porphyria in a patient?

A

Urine measurements of enzyme intermediates, particularly ALA and PBG

19
Q

What is the inheritance pattern of the porphyrias?

A

Autosomal dominant (except ALA dehydratase deficiency which is AR)

20
Q

What symptoms would you see in an acute intermittent porphyria patient?

A

Polyneuropaty
Painful abdomen
Port-colored urine (darkens b/c light oxidizes enzyme precursors)
Precipitated by drugs

21
Q

What is there long-term increased risk of in AIP patient?

A

Hepatocellular carcinoma

22
Q

How do you treat AIP?

A

Glucose and heme (IV) to inhibit heme synthesis pathway!

23
Q

What is the #1 porphyria?

A

Porphyria cutanea tarda (PCT)

24
Q

Is Porphyria cutanea tarda life-threatening?

25
If you have a patient with PCT (Porphyria Cutanea Tarda), what do you need to test for?
Hepatitis C b/c >50% of patients are positive
26
What are symptoms of PCT?
Photosensitivity Hyperpigmentation Hypertrichosis (hair growth) Bullous dermatosis (blistering skin lesions)
27
What is the pathogenesis of PCT?
For some reason, too much iron | ↑iron --> symptoms
28
What is Tx for PCT?
Reduce iron! Use phlebotomy or chelation
29
Discuss the malleability of RBCs
RBCs must be very malleable to fit through tiny capillaries and handle changes in tonicity Must also have high SA for gas exchange Membrane composed of complex cytoskeletal system
30
What are the important proteins involved in the RBC membrane cytoskeleton?
Ankryin Spectrin Actin
31
What can genetic defects of the RBC membrane cytoskeletal proteins lead to?
Inherited hemolytic anemias
32
What is hereditary spherocytosis?
Genetic defect in Spectrin protein -> less malleable RBCs | Less malleability --> premature RBC destruction in spleen
33
Morphology of RBC in Hereditary Spherocytosis?
Spherocyte: RBC is more of a sphere and less concave disk
34
Sx of Hereditary Spherocytosis?
Hemolysis & anemia Jaundice Splenomegaly
35
Tx of Hereditary Spherocytosis?
Splenectomy
36
How are damaged RBCs that are no longer deformable eliminated?
They are trapped in spleen and destroyed by macrophages