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Plasma lipids
Fatty acids
Cholesterol
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Lipoproteins
Disorders of lipid metabolism
Investigation of hyperlipidaemias
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FATTY ACIDS
CH3(CH2)nCOO
FATTY ACID
H3C
H3C
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3(CH2)nCOO
HO
CHOLESTEROL
CHOLESTEROL ESTER
O
O
1CH
2
O
R2 C O
O C R1
R2 C O
2CH
3CH
2
O C R2
1CH
O C R1
2CH
3CH
O
O P
O
TRIGLYCERIDE
PHOSPHOLIPID
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Lipoproteins
Table 13.1 Some of the major fatty acids found in the
plasma
Group
Monounsaturated
Polyunsaturated
Saturated
Name
Carbonchain length
Source
Palmitoleic
C16
Plant oil
Oleic
C18
Olive oil
Linoleic
C18
Plant oil
Linolenic
C18
Plant oil
Arachidonic
C20
Plant oil
Eicosapentaenoic
C20
Fish oil
Myristic
C14
Coconut oil
Palmitic
C16
Animal/plant oil
Stearic
C18
Animal/plant oil
Carbohydrate
Protein
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Fat
Glucose
Two-carbon
units
Fatty
acids
Triglyceride
Fatty
acids
Adipocyte
Fatty acid
Acyl CoA
Carnitine
Cytoplasm
Acyl carnitine
Matrix
Acyl CoA
-oxidation
Octanyl CoA
Dicarboxylic
acid
Beta oxidation
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Acetoacetyl CoA
3-hydroxy-3-methylglutaryl CoA
(HMG-CoA)
HMG-CoA REDUCTASE
Mevalonic acid
Isoprenoids
Squalene
Lanosterol
Cholesterol
Source
Composition (% mass)
Pro
Cho
Tg
PL
Apolipoprotein
Electrophoretic mobility
Chylomicrons
Gut
90
A, B, C, E
Origin
VLDL
Liver
25
55
12
B, C, E
Pre-b
LDL
20
55
20
HDL
Gut/liver
50
20
25
A, C, E
Cho, cholesterol; HDL, high-density lipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; PL, phospholipid; Pro,
protein; Tg, triglyceride; VLDL, very low-density lipoprotein.
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Lipoproteins
Table 13.3 Fredricksons classification of
hyperlipidaemias
Type
Electrophoretic
Increased lipoprotein
Increased chylomicrons
Chylomicrons
IIa
Increased b-lipoproteins
LDL
IIb
III
Broad b-lipoproteins
IDL
IV
Increased pre-b-lipoproteins
VLDL
2.2
(13.1)
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Function
A1
LCAT activator
A2
LCAT activator
B48
Secretion of
chylomicrons/VLDL
B100
C2
Lipoprotein lipase
activator
C3
Lipoprotein lipase
inhibitor
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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LIVER
Chylomicron
remnant
receptor
Chylomicron
remnant
E
HDL A
E
C
A
Chylomicron
NEFA
B
Capillary
wall
C
Lipoprotein
lipase
Apolipoprotein
GUT
Triglyceride
Cholesterol
Figure 13.5 Exogenous lipid pathways. HDL, high-density lipoprotein; NEFA, non-esterified (free) fatty acid.
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Lipoproteins
PERIPHERAL TISSUE
LIVER
NEFA
Glycerol
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LDL
receptor
LDL
receptor
B
Triglyceride
LDL
VLDL
A
B
HDL
E
C
IDL
C
NEFA
B
VLDL
VLDL
C
Capillary
wall
C
Lipoprotein
lipase
Apolipoprotein
Triglyceride
Cholesterol
Figure 13.6 Endogenous lipid pathways. HDL, high-density lipoprotein; IDL, intermediate-density lipoprotein;
LDL, low-density lipoprotein; NEFA, non-esterified (free) fatty acid; VLDL, very low-density lipoprotein.
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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High-density lipoprotein
Acetyl CoA
Nucleus
HMG-CoA
HMG-CoA reductase
Amino acids
Mevalonic acid
Lysosomal
degradation
CHOLESTEROL
+
ACAT
CHOLESTEROL
ESTERS
LDL receptor
B
LDL
Figure 13.7 The low-density lipoprotein (LDL) receptor. ACAT, acyl coenzyme A acyl transferase; CoA, coenzyme
A; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A.
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Bile salts
Liver
Cholesterol
ester
Discoid
HDL
Lecithin
Cholesterol
ester
Receptor
Lysolecithin
(bound to
albumin)
Spheroid
HDL
Cell
surface
A1
Cholesterol
A1
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Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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CASE 1
A 23-year-old woman had her plasma lipids checked
by her general practitioner because her father had
died of a myocardial infarction aged 44 years. Her
24-year-old brother had hyperlipidaemia. Her renal,
liver and thyroid function tests were normal, as was
her blood glucose.
Plasma (fasting)
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
00_CBMM_4147_BOOK_3rd.indb 210
06/12/2011 08:13
CASE 2
A 43-year-old man attended the vascular surgery outpatient clinic for peripheral vascular disease. He was
a non-smoker but had undergone a coronary artery
bypass graft the year before. Some of his laboratory
results were as follows:
Plasma (fasting)
211
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Cho
Tg
HDL
LDL
Statins
Fibrates
Ezetimibe
Nicotinic acid
w-3 fats
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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CASE 3
A 15-year-old woman presented to the surgical unit
with acute pancreatitis. Some of her laboratory
results were as follows:
Plasma (fasting)
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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Investigation of hyperlipidaemias
The blood sample should be taken to the laboratory
and assayed promptly. The usual fasting lipid profile
consists of plasma cholesterol, triglyceride and HDL
cholesterol concentrations.
When faced with a hyperlipidaemia, decide whether it
is primary or secondary. A family history, clinical features
and appropriate blood tests can be useful to help make
this decision. Lipid stigmata such as tendon xanthomata
or premature corneal arci may point to familial
hypercholesterolaemia, and tuberous xanthomata or
palmar striae to type III hyperlipoproteinaemia.
Blood glucose concentration is useful to help assess
for diabetes mellitus, liver function tests for liver disease
such as cholestasis, urinary protein and plasma albumin
concentrations for nephrotic syndrome and thyroid
function tests for hypothyroidism. It is also important
to determine alcohol consumption and medications
from the clinical history.
It is generally wise to retest patients lipids, a few
months apart, as it is recognized that the withinindividual variation of lipids can be significant, and
reliance cannot be placed on just one set of readings.
It is also useful to assess the patient for other
cardiovascular risk factors, including smoking habits,
diabetes mellitus, blood pressure, body weight and
family history of cardiovascular disease. These should
also be managed in their own right. Assessment should
also be made for possible atherosclerotic disease, for
example does the patient have evidence of coronary,
peripheral or carotid artery disease?
If the patient is known to have coronary artery
disease, aim for a plasma LDL cholesterol concentration
of about 2.0 mmol/L. Statins are first-line drugs for
patients with raised LDL cholesterol concentration.
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SUMMARY
Clinical Biochemistry and Metabolic Medicine 2012 Martin A. Crook / Hodder Education
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