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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
Erythropoietic porphyrias
location of deficient enzyme is in erythroid cell in bone marrow; skin rashes and blisters in childhood, liver failure or cirrhosis
26
Hepatic porphyrias
location of deficient enzyme is in liver
27
Chronic hepatic porphyrias
porphyria cutanea tarda: causes chronic liver disease, deficient uroporphyrinogen decarboxylase, accumulation of uroporphyriogen in urine and photosensitivity
28
Acute hepatic porphyrias
ALA dehydratase deficiencyl acute attacks after administration of drugs such as barbiturates
29
If enzymatic defect occurs BEFORE tetrapyrrole ring
abdominal and neuropsychiatric signs
30
If enzymatic defect occurs AFTER tetrapyrrole ring
photosensitivity (itching, burning, when exposed to light) due to formation of superoxideradicals from oxygen ROS
31
Chronic low levels of lead poisoning would lead to
increased protoporphyrin and increased ALA
32
RBA lifespan is
120d
33
Heme breakdown occurs in RES (reticuloendothelial system) of
Liver, Spleen, and lymph nodes
34
Heme oxygenase
catalyzes first step of heme degradation
35
Biliverdin
released from heme oxygenase reaction with CO2; green pigment
36
Biliverdin reductase
biliverdin forms bilirubin (red-orange)
37
Bile
bilirubin and derivatives
38
Unconjugated bilirubin
slightly soluble in plasma, must join albumin to be transported to liver
39
SULFONAMIDES
can displace albumin from bilirubin and bilirubin can enter CNS and cause neruronal damage
40
Ligandin
protein within hepatocytesthat the unconjugated bilirubin binds
41
Bilirubin glucuronyltransferase
within the hepatocyte, produces bilirubin diglucuonide (conjugated bilirubin) increased solubility
42
Conjugated bilirubin
excreted fro liver through bile canaliculi and into bile duct
43
Liver disease
problem secreting conjugated bilirubin into bile duct
44
Urobilinogen
conjugated bilirubin that has been hydrolyzed by the gut
45
urobilin
reabsorbed urobilinogen and excretion via kidneys
46
Stercobilin
MAJORITY of urobilinogen are oxidized and excreted in stool
47
ALT
highly specific for hepatocytes
48
AST
less specific for hepatocytes
49
ALP or ALK
intrahepatic biliary epithelial, sensitive
50
GGT
many tissues, confers organ specificity with ALP results
51
Albumin
Liver for liver disease
52
PT
liver - predicative
53
LDH
in many tissues - not very sensitive
54
5-NT
in hepatocytes and many tissues - confers organ specificity with ALP results
55
Hepatocellular disease
elevated ALT, possible AST (non-specific)
56
AST to ALT ratio of 2:1
alcohol abuse
57
AST and ALT > 1000
viral hepatitis
58
Diproportionately high ALT/AST levels compared to ALP
Hepatocellular disease - less specific
59
Low serum albumin
chronic disease liver damage
60
normal serum albumin
acute disease liver damage
61
Diproportionately high ALP to ALT/AST
Cholestasis
62
elevated 5'-NT
high specificity for hepatobiliary disease
63
High serum GGT
with elevated ALP - cholestasis, may indicate ingestion of drugs or alcohol, alcohol if only enzymes elevated
64
icterus
jaundice, deposition of bilirubin due to increased bilirubin blood levels
65
Hemolytic jaundice (anemia, g6pd)
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
Hepatocellular jaundice
Elevated ALT,AST, with intrahepatic cholestasis conjugated bilirubin is released into blood, elevated serum conjugated bilirubin (chronic: high levels of unconjugated serum bilirubin)
67
Obstructive jaunduce
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
Jaundice in newborns
Glucuronyl transferase activity is low (until 4 weeks), elevated bilirubin in excess of albumin binding capacity can cause encephaly
69
Water soluble bilirubin
direct, conjugated
70
Indirect bilirubin
unconjugated

Biochem 1502 (14 decks)

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