Heme Sythesis & Degradation Flashcards Preview

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Flashcards in Heme Sythesis & Degradation Deck (60):
1

Hemoglobin gives RBCs the ability to transport ________ throughout the body

Oxygen

2

Hemoglobin is composed of ____ globular sub-units each bound to an ______ containing _______

4

Iron

Heme

3

Heme has a heterocyclic __________ ring with ______ present in the center

Porphyrin

Iron

4

Each porphyrin ring contains ____ 5-membered rings. Each ring contains ______ connected by single ____________.

Each porphyrin contains FOUR 5-membered rings. Each ring contains NITROGEN and is connected by single CARBON BRIDGES.

5

Iron is present in hemoglobin is __________ state

Ferrous

6

Heme is present in __________, __________, &. ___________.

Hemoglobin, myoglobin, and cytochromes

7

Heme synthesis occurs primarily in what parts of the body?

Liver

Erythropoietin cells of bone marrow

8

Where does each phase of the biosynthesis of heme take place?

Phase I : mitochondria

Phase II : cytoplasm

Phase III: mitochondria

9

What are the starting ingredients of heme synthesis?

What inhibits the first step of the process?

Succinyl CoA and Glycine

Heme inhibits

10

In the synthesis of heme, what crossed the cytoplasmic barrier (from mitochondria to cytoplasm)?

ALA

11

In the synthesis of heme, what crosses the mitochondrial barrier (from cytoplasm to mitochondria)?

Copro-porphyrin open III

12

A defect in one or more stages of heme synthesis will lead to________

Porphyria

13

Which porphyria is autosomal recessive?
A) Variegated porphyria
B) Acute intermittent porphyria
C) Congenital erythropoietic porphyria
D) Porphyria cutanea tarda

C) Congenital erythropoietic porphyria

14

ALA Synthase is used in the first step of heme synthesis. In order to function, it needs ________ which has a cofactor of __________.

PLP (pyridoxal phosphate)

Vitamin B6

15

A deficiency in ALA-synthase or Vitamin B6 will cause ______

Anemia

16

In the first step of heme synthesis, Succinyl CoA is __________ producing a byproduct of CO2.

Decaroxylated

17

TRUE or FALSE: Porphyrias are INHERITED metabolic disorders.

TRUE

18

When you see neurological symptoms in a porphyria patient, you would expect what type of disease?

Acute hepatic

19

When you see skin issues and photosensitivity in a porphyria patient, you would expect what type of disorder?

Erythropoietic

20

Acute intermittent porphyria

Deficient enzyme: ?

Type of porphyria: ?

Autosomal recessive or dominant?

What is produced in excess?

Symptoms: ?

Porphobilinogen deaminase

Hepatic

Dominant

ALA and PBG

Neurological disfunction and abdominal pain

21

Congenital erythropoietic porphyria

Deficient enzyme: ?

Type of porphyria: ?

Autosomal recessive or dominant?

What is produced in excess?

Symptoms: ?

Uroporphyrinogen III (co)synthase

Erythropoietic

Recessive

Uroporphyrinogen I and its red-colored, air oxidation product uroporphyrin

Photosensitivity, red color in urine and teeth; hemolytic anemia

22

Porphyria Cutanea Tarda

Deficient enzyme: ?

Type of porphyria: ?

Autosomal recessive or dominant?

What is produced in excess?

Symptoms: ?

Uroporphyrinogen Decarboxylase

Hepatoerythropoietic

Dominant

Uroporphyrinogen III which converts to uroporphyrinogen I

Photosensitivity resulting in vesicles and bullpen on skin, red-wine colored urine

*Most common porphyria in the United States

23

Variegate porphyria

Deficient enzyme: ?

Type of porphyria: ?

Autosomal recessive or dominant?

Symptoms: ?

Protoporphyrinogen IX Oxidase

Hepatic

Dominant

Photosensitivity & Neurologic symtoms and developmental delay in children

*King George III

24

RBC undergo breakdown every ____ days and this is handled by the ______-endothelial system, which degrades ________
Globin is broken down into ______ and ______ which is removed for degradation.

120

Reticulo -endothelial

Hemoglobin

Amino acids & heme

25

Heme is what color in the body?

What enzyme converts heme to biliverdin?

Heme = purple

Heme oxygenase

26

What color is biliverden?

What enzyme converts biliverdin to bilirubin?

Biliverdin = green

Bilirubin reductase

27

What color is bilirubin in the body?

What does bilirubin associate with in the bloodstream?

Bilirubin = Red-orange

Albumin

28

In the liver, bilirubin requires what to go from "indirect" to "direct" - Bilirubin-monoglucuronide?

UDP-glucoronyl transferase

*rate-limiting rxn

29

In the liver, Bilirubin-monoglucuronide "indirect" requires what to go to Bilirubin-diglucuronide "direct"?

UDP-glucoronyltransferase

(Yes it's the same enzyme as the previous reaction)

*rate-limiting rxn

30

In the small intestine, bilirubin-diglucoronide goes to ________ which goes to _________.

Bilirubin

Urobilinogen

31

Urobilinogen can either stay in the ________ and go to ________ with the help of microbial enzymes to be excreted as ________ OR it can go to the ______ where it will be converted to __________ to be excreted as _________.

Small intestine
Stercobilin
Feces

Kidney
Urobilin
Urine

32

Which of the following is yellow and which is colorless?

Urobilinogen

Urobilin

Urobilinogen = colorless

Urobilin = yellow

33

Crigler-Najjar Syndrome and Gilbert syndrome are associated with a deficiency in what enzyme?

Glucuronyl transferase
<10% residual activity (CN)
25% residual activity (G)

34

The oxidation of heme liberates one of the ____________as ________,converts the________iron into ________iron and produces the green pigment __________.

Carbon bridges
CO (carbon monoxide)
Ferrous (Fe2+)
Ferric (Fe3+)
Biliverdin

35

Reduction of biliverdin produces the red-orange bilirubin that is conjugated in the _________, collected in _______ and secreted into the _____________,where it undergoes _____________ to urobilinogen

Liver
Bile
Small intestine
Microbial reduction

36

T or F: The iron in the porphyrin ring of heme is in the ferrous form.

True, the iron in heme is 2+ which is the ferrous form

The ferric form of iron is Fe3+

37

In heme degradation, the enzyme ___________ removes the bridge between pyrole rings of heme, releasing ________. Iron is oxidized from __________ to __________.

The enzyme used above is induced 100x by ______, _________ and __________.

Heme oxygenase
CO
Ferrous to ferric

Heme, metal ions, phenylhydrazine (a drug)

38

The enzyme responsible for degrading heme to biliverdin is _________. The enzyme used to take biliverdin to bilirubin is __________ and _______ is also needed.

Heme oxygenase

Biliverdin reductase
NADPH

39

Bilirubin is released into the bloodstream but because free/unconjugated/indirect bilirubin is _________, it is bound to _________.

Insoluble

Albumin

40

A protein carrier is needed for _________ uptake of bilirubin.

Bilirubin is conjugated with _________ to make it ________. This form is called _______ bilirubin.

Hepatic

Glucoronic acid
Soluble

Direct

41

What is the rate limiting step in the removal of bilirubin from blood?

If babies do not have sufficient amounts of this enzyme, they will get?

UDP glucoronyl transferase

Jaundice

42

Pre-hepatic jaundice indicates ________ production of ______________ bilirubin

An increased

Unconjugated

43

Excess hemolysis, internal hemorrhage, neonatal jaundice due to problems with incompatibility of maternal-fetal blood groups is associated with pre, intra or post hepatic jaundice?

Pre-hepatic jaundice

44

*With pre-hepatic jaundice, you would expect to see ______ blood levels of _______ or ________ bilirubin,
Normal levels of _______ BR

________ levels of ALT and AST.

And ______ would be present in urine but not ________.

Elevated

Unconjugated or indirect

Direct

Normal

Urobilinogen
Direct BR

45

Intra-hepatic jaundice is characterized by ___________ hepatic uptake, conjugation or secretions of conjugated BR.

Examples include?

Impaired (hepatic uptake)

Liver cirrhosis
Viral hepatitis
Criggler-Najjar syndrome
Gilbert syndrome

*Often due to drug abuse

46

With intra-hepatic jaundice, you would expect to see ______ in _________ and _________ bilirubin.


__________ in ALT and AST


__________ levels of urobilinogen in urine

And __________ detected in urine as well

Variable increases
Unconjugated and conjugated

Increases

Normal

Conjugated BR

47

Post-hepatic jaundice involves problems with ___________ and is also called ________ which means decrease _______ flow

Bilirubin excretion

Cholestasis

Bile

48

Post-hepatic involves obstruction to _______ drainage in _______ or _______ and can present as.....

Biliary

Liver or bile ducts

Gall stones, cholangiocarcinoma, infiltrative liver disease, lesions (tumor, abscess or granulomatous disease)

49

With post-hepatic, you would expect to see ________ blood levels of conjugated BR

_____ levels of ALT and AST

_______ ALP and bile salts

________ is present in urine, making it _______

And there is no _______ in feces so they are ______

Elevated

Normal

Elevated

Conjugated BR
Dark

Stercobolin
Pale

50

Autoimmune, abnormal hemoglobin are clinical examples of _________ jaundice

Prehepatic

51

Hepatitis A, B, C, acetaminophen or alcohol induced, Gilbert's syndrome, Crigler-Najjar syndrome, DUbin-Johnson Syndrome, Rotor's syndrome, Wilson's disease, neonatal are all clinical examples of __________ jaundice

Intrahepatic

52

Drug use, primary biliary cirrhosis, cholangitis, gall stones, pancreatic tumor, cholangiocarcinoma are all clinical examples of __________ jaundice

Post-hepatic

53

Gilbert's syndrome, Crigler-Najjar syndrome, Dublin-Johnson syndrome, Rotor's Syndrome are all clinical examples of intrahepatic jaundice due to ___________in bilirubin __________

genetic errors

Metabolism

54

Neonatal jaundice is also called _________ jaundice and is due to elevated __________ bilirubin.

Major contributing factors include:
-the breakdown of _______ as it is replaced with adult hemoglobin
-immature _______ metabolic pathways, unable to ________ and ______bilirubin
-deficiency of _______ enzyme

Physiological

Unconjugated

Fetal hemoglobin

Hepatic

Conjugate & excrete

UDP-GT

55

___________ is a common treatment for neonatal jaundice. The exposure to ________ turns bilirubin into a ________ form, which makes it easier to excrete.

Phototherapy

Light

Soluble

56

In ___________ syndrome type I, patients are born without _________ , in type II, patients are born with a mutated form of _______ resulting in _____ activity.

Criggler-Najjar

UDP-GT

UDP-GT

10%

57

*Criggler-Najjar Syndrome causes BR to ___________ in the _________ of ________,which causes___________and _________.

Therapy includes: ??

Accumulate in the brain of babies

Encephalopathy & brain damage

Blood transfusions, phototherapy, heme oxygenase inhibitors, oral calcium phosphate and carbonate,liver transplantation (before brain damage occurs and before phototherapy becomes ineffective)

58

Gilbert Syndrome results in __________ activity of __________ (enzyme) ___%

Serum BR may increase with _____, ______or ______

Gilbert syndrome affects ____ of the population

Reduced UDP-GT

25%

Fasting, stress or alcohol consumption

2-10%, relatively common

59

Hepatitis means ________ of the _________

Causes include viral infections such as ______, ______& ______, as well as _________ and __________

We see ______ levels of unconjugated and conjugated bilirubin in blood

Causes a _____ discoloration in the _____ and _______.

Urine is _______

Inflammation

Liver

Hep A, B & C
Alcoholic cirrhosis
Liver cancer

Elevated

Yellow
Skin and sclera of the eyes

Tea-colored (urine)

60

Bruises change colors based on the breakdown of ________ from ...

Heme which is ______
To ________ which is _______
To ________ which is _______
To _________ which is _______

Hemoglobin

Red/purple

Biliverdin=green

Bilirubin = orange/red

Hemosiderin = brown