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Biochem 1502 > Heme > Flashcards

Heme Flashcards

1
Q

Major sites of heme synthesis

A

liver and erythrocyte-producing bone marrow (85%)

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2
Q

heme degradation sites

A

reticuloendothelial cells in liver and spleen

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3
Q

porphyrin

A

cyclic compound that readily bind metal ions, cyclic ring of 4 pyrrole rings

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4
Q

Heme

A

prosthetic group for hemoglobin, myoglobin, cytochromes P450, etc; tetrapyrole ring + Fe2, final product in porphyrin biosynthesis

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5
Q

porphyrin structure

A

tetrapyrrole + Fe2; with side chain

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6
Q

Protoporphyrin IX (and heme)

A

contains vinyl and methyl and proprionate sidechains of porphyrin structure and HEME

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7
Q

porphyrinogens

A

intermediate between porphobilinogen and protoporphyrins

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8
Q

Type I uroporphyrin

A

alternating side chains of acetate and proprionate

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9
Q

Type II and IV uroporphyrin

A

not in nature

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10
Q

Type III uroporphyrin

A

same as type I but A and P are reversed

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11
Q

coproporphyrin

A

methyl and proprionate side chains

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12
Q

Heme structure

A

Fe2+ in center of protophorphyrin; final product of porphyrin synthesis

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13
Q

Formation of ALA

A

CAC intermediates provide C and N in porphyrin molecule (in MITOCHONDRIA) ALA SYNTHASE

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14
Q

ALA SYNTHASE

A

formation of ALA, RATE-LIMITING STEP, requires VITAMIN B6

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15
Q

Formation of porphobilinogen

A

2 ALA molecules condense via ALA dehydratase

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16
Q

ALA Dehydratase

A

froms porphobilinogen, contains zinc, LEAD POINSONING will inhibit this enzyme

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17
Q

Formation of Heme

A

Coproporphyrinogen III enters back into mitochondria for decarboxylation and oxidation to protoporphyrin IX

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18
Q

Fe2+ enters spontaneously

A

Ferrochelatase enzyme enhances the speed, also inhibited by LEAD

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19
Q

ALA synthase inhibitors

A

HEME accumulation and conversion to HEMIN (Fe3+)

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20
Q

Barbiturates (phenobarbital)

A

INCREASE ALA Synthase activity (cytochrome P450)

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21
Q

Cytochrome P450 production

A

enhances utilization of heme, decreased heme in liver, increased ALA synthase “deprepression”

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22
Q

Lead inhibits heme formation

A

ALA dehydratase and ferrochelatase (zinc containing and sensitive to heavy metals like lead

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23
Q

Lead poisoning

A

elevated ALA and anemia

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24
Q

porphyrias

A

defects in heme synthesis (rare) ALA synthase increases; autosomal dominant

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25
Q

Erythropoietic porphyrias

A

location of deficient enzyme is in erythroid cell in bone marrow; skin rashes and blisters in childhood, liver failure or cirrhosis

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26
Q

Hepatic porphyrias

A

location of deficient enzyme is in liver

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27
Q

Chronic hepatic porphyrias

A

porphyria cutanea tarda: causes chronic liver disease, deficient uroporphyrinogen decarboxylase, accumulation of uroporphyriogen in urine and photosensitivity

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28
Q

Acute hepatic porphyrias

A

ALA dehydratase deficiencyl acute attacks after administration of drugs such as barbiturates

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29
Q

If enzymatic defect occurs BEFORE tetrapyrrole ring

A

abdominal and neuropsychiatric signs

30
Q

If enzymatic defect occurs AFTER tetrapyrrole ring

A

photosensitivity (itching, burning, when exposed to light) due to formation of superoxideradicals from oxygen ROS

31
Q

Chronic low levels of lead poisoning would lead to

A

increased protoporphyrin and increased ALA

32
Q

RBA lifespan is

A

120d

33
Q

Heme breakdown occurs in RES (reticuloendothelial system) of

A

Liver, Spleen, and lymph nodes

34
Q

Heme oxygenase

A

catalyzes first step of heme degradation

35
Q

Biliverdin

A

released from heme oxygenase reaction with CO2; green pigment

36
Q

Biliverdin reductase

A

biliverdin forms bilirubin (red-orange)

37
Q

Bile

A

bilirubin and derivatives

38
Q

Unconjugated bilirubin

A

slightly soluble in plasma, must join albumin to be transported to liver

39
Q

SULFONAMIDES

A

can displace albumin from bilirubin and bilirubin can enter CNS and cause neruronal damage

40
Q

Ligandin

A

protein within hepatocytesthat the unconjugated bilirubin binds

41
Q

Bilirubin glucuronyltransferase

A

within the hepatocyte, produces bilirubin diglucuonide (conjugated bilirubin) increased solubility

42
Q

Conjugated bilirubin

A

excreted fro liver through bile canaliculi and into bile duct

43
Q

Liver disease

A

problem secreting conjugated bilirubin into bile duct

44
Q

Urobilinogen

A

conjugated bilirubin that has been hydrolyzed by the gut

45
Q

urobilin

A

reabsorbed urobilinogen and excretion via kidneys

46
Q

Stercobilin

A

MAJORITY of urobilinogen are oxidized and excreted in stool

47
Q

ALT

A

highly specific for hepatocytes

48
Q

AST

A

less specific for hepatocytes

49
Q

ALP or ALK

A

intrahepatic biliary epithelial, sensitive

50
Q

GGT

A

many tissues, confers organ specificity with ALP results

51
Q

Albumin

A

Liver for liver disease

52
Q

PT

A

liver - predicative

53
Q

LDH

A

in many tissues - not very sensitive

54
Q

5-NT

A

in hepatocytes and many tissues - confers organ specificity with ALP results

55
Q

Hepatocellular disease

A

elevated ALT, possible AST (non-specific)

56
Q

AST to ALT ratio of 2:1

A

alcohol abuse

57
Q

AST and ALT > 1000

A

viral hepatitis

58
Q

Diproportionately high ALT/AST levels compared to ALP

A

Hepatocellular disease - less specific

59
Q

Low serum albumin

A

chronic disease liver damage

60
Q

normal serum albumin

A

acute disease liver damage

61
Q

Diproportionately high ALP to ALT/AST

A

Cholestasis

62
Q

elevated 5’-NT

A

high specificity for hepatobiliary disease

63
Q

High serum GGT

A

with elevated ALP - cholestasis, may indicate ingestion of drugs or alcohol, alcohol if only enzymes elevated

64
Q

icterus

A

jaundice, deposition of bilirubin due to increased bilirubin blood levels

65
Q

Hemolytic jaundice (anemia, g6pd)

A

massive lysis of RBCs, access of bilirubin can’t all be conjugated, increased serum unconjugated bilirubin, and increased urobilinogen and urobilin leading to dark urine

66
Q

Hepatocellular jaundice

A

Elevated ALT,AST, with intrahepatic cholestasis conjugated bilirubin is released into blood, elevated serum conjugated bilirubin (chronic: high levels of unconjugated serum bilirubin)

67
Q

Obstructive jaunduce

A

extrahepatic cholestasis; tumor, bile stones, stool is light in color, conjugated bilirubin high in serum, urine is dark red-orange, urinary urobilinogen is absent (chronic: unconjugated bilirubin)

68
Q

Jaundice in newborns

A

Glucuronyl transferase activity is low (until 4 weeks), elevated bilirubin in excess of albumin binding capacity can cause encephaly

69
Q

Water soluble bilirubin

A

direct, conjugated

70
Q

Indirect bilirubin

A

unconjugated

Biochem 1502 (14 decks)

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