Iron is neat!

Question 1

What are hemes used in?

Answer 1

Cyt p450 and hemo/myoglobin

Question 2

Hemoglobin is made of ______ globular subunits, the iron in the ring is in the ____________ state.

Answer 2

4, ferrous

Question 3

Where does heme synthesis take place?

Answer 3

Phase I in mitochondria, II in cytosol, III in mitochondria

Question 4

What is the rate limiting step in heme synthesis? What is it catalyzed by?

Answer 4

The rate limiting step is the conversion of glycine and succinyl-CoA to delta-aminolevulinic acid (ALA) by ALA synthase

Question 5

What does ALA synthase require? What is it inhibited by?

Answer 5

PLP (B6), inhibited by heme and hemin

Question 6

Acute intermittent porphyria is a problem in the _____________ enzyme and this process is related to __________ synthesis

Answer 6

Porphobilinogen deaminase (porphobilinogen -> hydroxymethylbilane) , hepatic

It is autosomal dominant

Question 7

Congenital erythropoietic porphyria is an issue with the ___________________ enzyme and it is involved in what system?

Answer 7

Uroporphyrinogen III synthase (hydroxymethylbilane -> uroporphyrinogen III), erythocyte defect

It is autosomal recessive

Question 8

What is the most common porphyria?

Answer 8

Porphyria cutanea tarda, problems with uroporphyrinogen decarboxylase (uroporphyrinogen III -> coproporhyrinogen III) and it is an issue in both hepatocytes and erythrocytes

It is autosomal dominant

Question 9

Describe variegate porphyria

Answer 9

It is hepatic, defect in protoporphyrinogen oxidase (protoporphyrinogen IX -> protoporphyrin IX), the penultimate step in heme synth.

It is autosomal dominant

Question 10

Lead affects what steps in heme synthesis?

Answer 10

1. The last step, ferrochelatase (protoporphyrin IX-> heme)

2. First cytosolic step, ALA dehydratase (2 ALA -> porphobilinogen)

Question 11

Drug related porphyria affects what step?

Answer 11

The last step, ferrochelatase (protoporphyrin IX -> heme)

Question 12

What tint are urine and feces in most porphyria?

Answer 12

Dark

Question 13

How often are RBC recycled?

Answer 13

Every 120 days

Question 14

What does hemoglobin breakdown yield?

Answer 14

Globin -> AA, heme->degraded

Question 15

Conjugated bilirubin contains bilirubin and what?

Answer 15

UDP glucuronic acid

Question 16

Jaundice is caused by an abundance of _____________ bound to _________________ in the blood

Answer 16

Bilirubin and albumin

Question 17

What are the final breakdown products of hemes? Where are they excreted?

Answer 17

Urobilin (yellow color of urine), stercobilin (red-brown color of feces)

Question 18

During heme breakdown, iron is taken from the ____________ (__+) state to the _______________ (__+) state.

Answer 18

Ferrous, 2, ferric, 3

Question 19

Heme oxygenase 1 is inducible by Nrf2, which is ubiquitinated and destroyed when not active much like what protein in epithelial architecture?

Answer 19

Beta-care in

Question 20

In the small intestine, microbes concert bilirubin to colorless _____________

Answer 20

Urobilinogen

Question 21

What are the three types of jaundice?

Answer 21

Pre-hepatic, intra-hepatic, post-hepatic

Question 22

CC: Direct and indirect Bilirubin

Answer 22

Unconjugated bilirubin is insoluble in the blood

Conjugated (to glucuronate) bilirubin is soluble

Question 23

Congenital Erythropoietic porphyria

Answer 23

Results from a deficiency of uroporphyrinogen III cosynthase
Key intermediates are diverted to the nonfunctional uroporphyrinogen I isomer that produces red color in ruin, teeth, premature destruction of erythrocytes and skin sensitivity

Question 24

Color changes in bruises

Answer 24

Cleanup of the pooling of blood typical of a bruise by macrophages leads to degradation of hemoglobin to heme (red), biliverdin (green), and bilirubin (reddish yellow)
Formation of these degradation products manifests as visible color change of bruise

Question 25

Neonatal jaundice

Answer 25

Due to low level of conjugating enzyme at birth
Exacerbated by premature birth
Pathological jaundice can result from blood group incompatibility or liver dysfunction

Excess unconjugated bilirubin (>15mg/dL) can diffuse into the basal ganglia and cause toxic encephalopathy (kernicterus)

Treat with blue fluorescent lights

Question 26

UDP-glucuronyl transferase-related disorders

Answer 26

Criggler-Najjar results from deficiency of UDP-glucuronyl transferase
Type 1 - complete absence of gene > sever hyperbilirubinemia that accumulates in the brain and causes kernicterus
Type II - mutation causes partial deficiency (<25% activity) serum bilirubin is <6mg/dL unless fasting, stressed, or boozing

Question 27

Hepatitis

Answer 27

Inflammation of the liver that leads to hepatic dysfunction
Causes increased levels of conjugated and unconjugated bilirubin
Conjugated bilirubin accumulation in the skin and sclera of eyes manifests as yellow coloration

Question 28

What is the key feature of pre-hepatic jaundice?

Answer 28

Increased production of unconjugated BR but have normal ALT and AST

Question 29

What are the key findings of intra-hepatic jaundice?

Answer 29

Variable increased in both conj. and unconj. BR, increase in serum ALT AST, conjugated BR in urine

Question 30

What are the key clinical findings in post hepatic jaundice?

Answer 30

Elevated BR in blood, normal serum AST and ALT, elevated alkaline phosphatase, elevated levels of bile salts, no urobilin and stercobilin

Question 31

Neonatal jaundice is a type of ________________ jaundice

Answer 31

Intrahepatic

Question 32

Neonatal jaundice is a deficiency in _________________

Answer 32

UDP-GT enzyme

Question 33

Crigler-Najjar syndrome is a deficiency in what enzyme?

Answer 33

UDP-GT

Question 34

What are some common treatments for UDP-GT disorders?

Answer 34

Blood transfusions (infuse blood not loaded with BR), phototherapy (help with breakdown), heme oxygenase inhibitors (slow down the breakdown process to slow accumulation), oral CaPO4 and CO3 (forms complexes with BR in gut), liver transplant

Question 35

Which UDP-GT disorder is often benign?

Answer 35

Gilbert syndrome (UDP-GT functions at 25%)

Question 36

What are some causes of hepatitis?

Answer 36

Hep A, B, c; alcoholic cirrhosis; liver cancer

Question 37

What are the physical symptoms of hepatitis?

Answer 37

BR turns sclera and skin yellow; dark, tea-colored urine