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Biochemistry and Metabolism

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Biochemistry and Metabolism The course will cover: Enzymes kinetics and control Control of metabolism Control of metabolism is the control of enzyme activity – PowerPoint PPT presentation

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Title: Biochemistry and Metabolism


1
Biochemistry and Metabolism
  • The course will cover
  • Enzymes kinetics and control
  • Control of metabolism
  • Control of metabolism is the control of enzyme
    activity

2
Biochemistry and Metabolism
  • Why should we study metabolism?
  • Why is metabolism interesting?
  • Where does metabolism feature in daily life?
  • Why should we study enzymes?
  • Why are enzymes interesting?
  • How do enzymes feature in daily life?

3
from Drug Discovery Today 11 481-493 (2006)
4
statins Inhibitors of the enzyme HMG CoA
reductase
5
HMG CoA reductase
HMG CoA NADPH ? mevalonate NADP Rate
limiting, regulatory enzyme in cholesterol
synthesis
6
Cholesterol and heart disease
  • Cholesterol as key factor
  • Excessive deposition in blood vessels leads to
    heart disease
  • Carried as lipoproteins
  • bad cholesterol low density lipoprotein (LDL)
  • good cholesterol high density lipoprotein
    (HDL)

7
Benefits of Lipitor
  • Lowers total cholesterol by 40.
  • Lowers "bad," low-density lipoprotein (LDL)
    cholesterol by 50.
  • Reduces risk for heart attack and stroke

8
Every five minutes somebody in the UK dies from a
heart attack
9
Office of National Statistics (2005) Scotland
General Register Office (2005) Northern Ireland
General Register Office (2005)

www.heartstats.org
10
Risk factors for heart disease
  • High fat diet
  • Overweight/obese
  • High blood pressure
  • Smoking
  • Lack of exercise
  • Heredity

11
Increase in obesity
12
Overweight/obesity BMI 25 kg/m2 and over Health
Survey for England 2004 Scottish Health Survey
2003 Welsh Health Survey 2003/04
www.heartstats.org
13
(No Transcript)
14
lifestyle
more
less
15
diet
Guideline daily amount
Food Standards Agency traffic light labelling
16
Metabolic syndrome
  • Obesity, particularly around the waist (having an
    "apple shape")
  • 2. Elevated blood pressure
  • 3. An elevated level of triglycerides and a low
    level
  • of high-density lipoprotein (HDL) the "good"
    cholesterol
  • 4. Resistance to insulin

17
Metabolic syndrome
Prevalence 20 of adults in US
Risk Factors poor eating habits, lack of
exercise, genetics, ageing
18
Metabolic syndrome
  • Increased risk of heart disease
  • Increased risk of Type 2 diabetes

19
Questions to ask about diet and metabolism
  • How does a high carbohydrate diet lead to
    obesity?
  • How does a high fat diet lead to heart disease?
  • What is disturbed in diabetes?

20
Complex interplay between glucose/fat/cholesterol
metabolism
21
Need to understand diet and metabolism
  • Daily Mail
  • August 20th 2002 Could this be the cure for
    obesity?
  • July 30th 2003 Chemical could burn away obesity
  • Gillian McKeith she hasn't a clue about
    nutrition (Brit Dietetic Assn)

22
Biochemistry and Metabolism
  • Why should we study enzymes?
  • Why are enzymes interesting?
  • How do enzymes feature in daily life?

23
Enzymes?
  • Biological washing powders
  • Drug targets
  • Tests for disease/test kits
  • Clinical tests for liver damage

24
Biological washing powders
Contain lipases and proteases to digest fat and
protein in stains Work at lower temperatures
25
Drug targets
Inhibitors of enzyme COX-2 (cyclooxygenase-2,
responsible for prostaglandin synthesis)
26
ELISA
  • Enzyme Linked ImmunoSorbant Assays
  • Used widely for detection of proteins and
    antibodies in patient samples
  • Uses enzyme conjugated to antibody

27
Test for HIV
  • Patients with HIV have antibodies against the
    viral proteins
  • Detect these antibodies using ELISA

28
96 well plate for ELISA
29
ELISA for antibodies in HIV
Enzyme-labelled Anti-human antibody
Colour development after adding substrate for
enzyme
?
?
Patient sample Containing anti HIV
HIV proteins
30
ELISA
  • Detection antibody has enzyme attached to it
  • e.g. alkaline phosphatase substrate
    4-nitrophenyl phosphate


yellow
colourless
31
96 well plate for ELISA
32
Pregnancy test kits
33
Tests for liver function
  • Doctor requests liver enzymes
  • Blood test
  • Measure total protein, albumin and several
    enzymes in serum

34
Liver enzymes
  • Alanine aminotransferase
  • Aspartate aminotransferase
  • Enzymes involved in amino acid metabolism

35
Liver enzymes in blood sample
  • Alanine aminotransferase
  • Leaks in to blood from damaged liver cells e.g.
    viral hepatitis, paracetamol overdose, fatty
    liver (alcohol abuse) etc
  • Aspartate aminotransferase
  • Also raised in liver damage but not as specific

36
What do we need to know about enzymes?
  • How to set up an enzyme assay
  • Effects of inhibitors
  • How to interpret the results

37
HMG CoA reductase assay
HMG CoA NADPH ? mevalonate NADP Assay
from loss of absorbance at 340 nm as NADPH
consumed Mix enzyme and substrate in cuvette and
read A340
38
Kinetics of enzymes
initial rate
39
Effect of statin on HMG CoA reductase activity
40
Effect of statin on HMG CoA reductase activity
Competitive inhibition
from FEBS Letts 72 323-326 (1976)
41
Enzyme assays in real life
Hospital pathology lab
Industrial drug discovery
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