Alcohol metabolism – the role of K M Cytosolic Acetaldehyde dehydrogenase K M value - high Mitochondrial Acetaldehyde reductase K M value - low CH 3 CH 2 OH NAD+ CH 3 CHO H + NADH CH 3 CHO NAD+ H + NADH CH 3 COOH + + + A lkohol dehidrogenáz + + + A cetaldehid dehidrogenáz TACHYCARDIA
Alcohol metabolism – the role of K M. TACHYCARDIA. Mitochondrial Acetalde hyde redu ctase K M value - low. Cytosolic Acetaldeh y d e dehydrogenase K M value - high. Enzymes - K M values. K M. K M ~ Dissociation constant for ES , if k 2 >> k 3 - PowerPoint PPT Presentation
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Alcohol metabolism – the role of KM
Cytosolic AcetaldehydedehydrogenaseKM value - high
Mitochondrial Acetaldehyde
reductaseKM value - low
CH3 CH2 OH NAD+
CH3 CHO
H+
NADHCH3 CHO
NAD+ H+
NADHCH3 COOH
+ + +
Alkoholdehidrogenáz
+ + +
Acetaldehiddehidrogenáz
TACHYCARDIA
Enzymes - KM values
Enzyme Substrate KM
Chymotrypsin Acetil-L-Trp 5000 mM
ß-Galaktosidase Lactose 4000 mM
Penicillinase Benzylpenicillin 50 mM
KM
1
32M k
kkK
E + S E + PES
k1
k2
k3
32 kk 1
2M k
kK
1
2ES k
k
[ES]
[S]*[E]K
KM ~ Dissociation constant for ES, if k2 >> k3
KM value is high: ES formation is weakKM value is low : assotiation
Importance of the Vmax value
Turnover number:
t3max [E]kV tmax3 /[E]Vk
Enzyme Turnover number / sec
Carbonic anhydrase 600000
Acetylcholin esterase 25000
Tryptophan synthetase 2
Inhibition of Enzymes
• Irreversible– Ser-OH– Cys-SH
• Reversible
CH2 OH
C
H
CH3H3C
O
P
O
OF
C CH3H3C
H
+
C
H
CH3H3C
O
P
O
O
C CH3H3C
H
OCH2Enzim Enzim
Diizopropil-fluorofoszfát
+ HFEnzyme Enzyme
Diisopropylfluorophosphate
Inhibitions of enzymes
Enzim EnzimCH2 SH ICH2 C NH2
O
+ CH2 S CH2 C NH2
O
HFMonojód acetamid
•-SH enzymes
+ HIEnzyme Enzyme
monoiodacetamide
Competitive inhibition of succinate-dehydrogenase by malonate
COO-
CH2
CH2
COO-
COO-
CH
CH
COO-
COO-
CH2
COO-
COO-
COO-
COO-
CH2
C
COO-
O
PO O
O
O
P
O
OO
FAD FADH2
Succinate-dehydrogenase
malonate
Oxalate
Oxaloacetate
pyrophosphate
Competitive inhibition
+ S
+ I
E + S ES E + P
I
EI
Ki
+
EI
I*EK i
Ki = dissociation constant for complex
Competitive inhibition of succinate-dehydrogenase by malonate
[Inhibitor 1]
[Enzyme]
[Inhibitor 2]
No inhibitor
Substrate+ competitive inhibitor
Competitive inhibition
+ S
+ I
E + S ES E + P
I
EI
Ki
+
EI
I*EK i
Ki = Dissociation constans of complex
+P
Competitive inhibition of succinate-dehydrogenase by malonate