Alcohol metabolism the role of KM

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Alcohol metabolism the role of KM
TACHYCARDIA
Mitochondrial Acetaldehyde reductase KM value -
low
Cytosolic Acetaldehyde dehydrogenase KM value -
high
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Enzymes - KM values
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KM
KM Dissociation constant for ES, if k2 gtgt
k3 KM value is high ES formation is weak KM
value is low assotiation
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Importance of the Vmax value
Turnover number
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Inhibition of Enzymes

• Irreversible
• Ser-OH
• Cys-SH
• Reversible

HF
Enzyme
Enzyme
Diisopropylfluorophosphate
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Inhibitions of enzymes

• -SH enzymes

HI
Enzyme
Enzyme
monoiodacetamide
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Competitive inhibition of succinate-dehydrogenase
by malonate
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Competitive inhibition
S
I
Ki dissociation constant for complex
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Competitive inhibition of succinate-dehydrogenase
by malonate
No inhibitor
Enzyme
Substrate
competitive inhibitor
Inhibitor 1
Inhibitor 2
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Competitive inhibition
P
S
I
Ki Dissociation constans of complex
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Competitive inhibition of succinate-dehydrogenase
by malonate
V mM/min
Vmax
Enzyme without ihhibitor
Enzyme inhibitor (1)
Vmax/2
Enzyme inhibitor (2)
Substrate M
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Competitive inhibition
E inhibitor-2
E inhibitor-1
1/v
Enzyme alone
1/VMAX
1/S
yaxb
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Competitive inhibition Lineweawer-Burk plots
Enzyme Inhibitor 2
Enzyme Inhibitor 1
Enzyme
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Competitive inhibition

• KM value - increase, Vmax - constant
• KI / KS
• Inhibition depends on S/I.

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Competitive inhibition
E inhibitor2
E inhibitor1
1/v
Enzyme only
1/VMAX
1/S
yaxb
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Inhibitions
Ethanol
N Methanol
N Ethyleneglycol
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Ethanol
N Methanol
N Ethyleneglycol
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Competitive inhibition
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Noncompetitive inhibition
S
I
P
S
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Noncompetitive inhibition

• KM value is constant
• VMax - decrease
• Inhibitor-binding different of substate binding
  site
• EIS complex is inactive

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Nonkompetitive inhibition
I2
1/v
I1
Kontroll
1/Vmax
-1/KM
1/S
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Noncompetitive inhibition
Metal / Enzyme CN-, EDTA
Partially noncompetitive inhibitor
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Uncompetitive inhibition
Both KM Vmax values - decrease
1/v
I1
Enzyme alone
1/S
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Inhibition of mixed type
KM - increase Vmax decrease
1/v
I1
Control
1/S
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Turnover number

• Number of molecules converted by 1 molecule of
  enzyme
• Vmax k3Et
• k3 sec-1
• i.e. 10-6 M carbonic anhydrase
• 0.6 M of H2CO3 in 1 secundum

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Turnover number
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Activity units

• Enzyme activity units
• 1 E (U) 1 mmole/min 25 oC
• 1 Catal (SI) 1 mole/sec
• Specific activity
• mmo/min/mg protein
• mol/sec/mg protein

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Enzyme activities in everyday medical practice
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Enzyme activities in everyday medical practice
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Specific enzyme activity