Upload
imogene-griffith
View
212
Download
0
Embed Size (px)
Citation preview
Cholesterol sources, biosynthesis and degradation diet
only found in animal fat
biosynthesis primarily synthesized in the liver from acetyl
CoA biosynthesis is inhibited by LDL uptake by
the liver
degradation only occurs in the liver cholesterol is converted to bile acids
Biosynthesis summary
glyceride in which the glycerol is esterified with three fatty acids. It is the main constituent of
vegetable oil and animal fats.
Triglycerides
Cont…
Triglycerides, as major components of very low density lipoprotein (VLDL) and chylomicrons.
play an important role in metabolism as energy sources and transporters of dietary fat. They contain more than twice as much energy (9 kcal/g) as carbohydrates and proteins.
Cont…
In the intestine, triglycerides are split into glycerol and fatty acids (this process is called lipolysis) (with the help of lipases and bile secretions), which are then moved into the cells lining the intestine (absorptive enterocytes).
Cont…
The triglycerides are rebuilt in the enterocytes from their fragments and packaged together with cholesterol and proteins to form chylomicrons.
These are excreted from the cells and collected by the lymph system and transported to the large vessels near the heart before being mixed into the blood.
Cont…
Various tissues can capture the chylomicrons, releasing the triglycerides to be used as a source of energy.
Fat and liver cells can synthesize and store triglycerides.
When the body requires fatty acids as an energy source, the hormone glucagon signals the breakdown of the triglycerides by hormone-sensitive lipase to release free fatty acids.
Cont…
As the brain can not utilize fatty acids as an energy source, the glycerol component of triglycerides can be converted into glucose for brain fuel when it is broken down.
Fat cells may also be broken down for that reason, if the brain's needs ever outweigh the body's. HDL is the most helpful in preventing coronary heart disease.???
Triglycerides
Associated with increased risk of CHD events
Link with increased CHD risk is complex may be related to low HDL levels and
highly atherogenic forms of LDL cholesterol
May have accompanying dyslipidaemias
Normal triglyceride levels <200mg/dl
(2.3mmol/l) Very high level of triglycerides
(>1000mg/dl, 11.3mmol/l) is associated with increased pancreatitis risk
Reducing triglyceride levels Moderating the consumption of fats
and carbohydrates and aerobic exercise are essential to reducing triglyceride levels.
Omega-3 fatty acids from fish, flax seed oil, or other sources (on the order of 5 grams of omega-3 per day) or Omega-6 fatty acids.
one or several grams of niacin (mega-dose vitamin B-3) per day and some statins reduce triglyceride levels.
Cont…
Fibrates have been used in some cases as some fibrates can bring down TGs substantially.
However they are not used in first line as they can have unpleasant or dangerous side effects.
In one case due to an increase in mortality, clofibrate was withdrawn from the North American market.
Alcohol abuse can cause elevated levels of triglycerides.
Possible Atherogenic Changes Accompanying Hypertriglyceridemia
Hypertriglyceridemia
Increasedchylomicron
remnants
Small,dense LDL
Coagulationchanges
Increased VLDL cholesterol-rich
remnantsLow HDL
Miller M. Eur Heart J. 1998;19(Suppl H):H18-H22.
Risk of CHD by Triglyceride Level(The Framingham Heart Study)
N=5127
Castelli WP. Am J Cardiol. 1992;70: 3H-9H.
Rel
ativ
e R
isk
Triglyceride Level (mg/dL)
Frederickson -WHO classification
Type I: incr. chylomicrons, reduced HDL, absence of lipoprotein lipase; deficiency of apo CII (hyperchylomironemia)
Type II-A: raised LDL; decreased catabolism of LDL (receptor deficiency or polygenic)
Type II-B: raised VLDL + LDL; often reduced HDL; increased production of VLDL + impaired LDL catabolism
CONT…
Type III: raised IDL (dysbetalipoproteinemia); abnormal apolipoprotein E; impaired catabolism of IDL; elevated cholesterol and triglycerides (formerly known as broad beta disease)
CONT…
Type IV: raised VLDL; often reduced HDL; impaired VLDL catabolism; dietary indiscretion ( formerly known as hyperprebetalipoproteinemia)
Type V: raised chylomicrons + VLDL; reduced HDL; reduced lipoprotein lipase + VLDL hypersecretion (formerly known as mixed lipemia)
Classification of DyslipidaemiasFredrickson (WHO) Classification
LDL – low-density lipoprotein; IDL – intermediate-density lipoprotein; VLDL – very low-density lipoprotein. (High-density lipoprotein (HDL) cholesterol levels are not considered
in the Fredrickson classification.)
Phenotype
I
IIa
IIb
III
IV
V
Lipoproteinelevated
Chylomicrons
LDL
LDL and VLDL
IDL
VLDL
VLDL and chylomicrons
Atherogenicity
None seen
+++
+++
+++
+
+
Prevalence
Rare
Common
Common
Intermediate
Common
Rare
Serumcholesterol
Normal to
Normal to
Normal to
Serumtriglyceride
Normal
(Adapted from Yeshurun et al., 1995)