Note Midterm - 4 March in class

Note

Midterm - 4 March in class

Note

Signal peptide-A sequence of amino acids that determine whether a protein will be formed on the rough endoplasmic reticulum or on free ribosomes. Note: all protein synthesis begins on free ribosomes.

http://biotech.icmb.utexas.edu/search/dict-search.phtml?title=sequenc

Conversion of 70 mg/dl glucose to 3.9 mmol/L

Lecture 5a 3 Feb. 2014 Atherosclerosis

Pathology-5a

Nutritional Intervention-5b

Functional Food/Nutraceutical Approaches-5c

Atherosclerosis-Pathology

LDL and Lp(a) deposits lipid in artery wallHDL removes lipid from artery wall

Roles of LCAT, LPL, CETP in these processes

Aggregated platelets also clog up arteries

Factors affecting atherosclerosisBlood Levels of concern-the more risk factors

(eg obesity and in particular abdominal obesity) the lower the cut off points for

LDL-cHDL-c < 0.90 mmol/L plasma

LDL-c > 3.40 mmol/L plasmaincluding oxidized LDL

Lp(a) - > 20-30 mg/dl plasma Cholesterol > 5.20 mmol/L Triglycerides-fasting > 1.70 mmol/L

plasma -post-prandial

Factors affecting atherosclerosisBlood Levels of concern-the more risk factors

(eg obesity and in particular abdominal obesity) the lower the cut off points for

LDL-c

Risk Category Risk LDL-c level Cholesterol:HDL-c ratio

High > 20 %** < 2.0 mmol/L < 4.0

Moderate 11-19 % < 3.5 mmol/L < 5.0

Low < 10 % < 5.0 mmol/L < 6.0

** or history of diabetes or any atherosclerotic disease - Can. J. Cardiol 22: 913-end

September 2006

Factors affecting atherosclerosis

Triglycerides and small dense LDL

As plasma triglyceride levels rise there is a greater percentage of small dense LDL

-small dense LDL is taken up very aggressively into artery wall

Triglycerides and low HDL

-this is due to low LPL activity


Macrophages

Oxidation of LDL results in the binding of monocytes to the endothelial cells lining the vessel wall. These monocytes are activated and migrate into the endothelial space where they are transformed into macrophages, leading to further oxidation of the LDL. The oxidized LDL is taken up through the scavenger receptor on the macrophage, leading to the formation of foam cells.


-aggregated platelets also clog up the arteries

Factors affecting atherosclerosisPlateletsCollagen is the aggregation kick off followed by the pro-aggregatory ADP and TxA2

Aggregation affected by:Platelet membrane phospholipid fatty acid

composition -cyclooxygenase produces prostaglandins -lipoxygenase produces leukotrienes

-review arachidonic acid displacement

Decreased platelet membrane fluidity -if cholesterol:phospholipid ratio increased

-if degree of membrane fatty acid saturation increased

-results in increased platelet aggregation

-


Platelets interactions with lipoproteins

Interaction with lipoproteinsHDL-lowers aggregationLDL-elevates aggregation

Lp (a)-depresses platelet aggregation though also thought to inhibit plasminogen activation


Blood pressure damage vascular wall causing increased LDL influx

Factors affecting blood pressure:-Water content of blood-renal function-Vasodilation-Vasoconstriction

Values of concern- > 140 (systolic) or > 90 (diastolic) or >

140/90- significance of these values

Factors affecting atherosclerosisObesity

-measures waist circumference

waist to hip and waist to height BMIskin foldsunderwater weighingapple/pear shape

-obesity causes the following: -elevated blood pressure and renal disease -elevated plasma triglycerides -elevated plasma LDLc and sd LDLc -decreased plasma HDLc


Renal Disease

-urea builds up in blood and is toxic to endothelium (results in reduced vasodilation)

-renal disease causes further elevated blood pressure due to reduced water clearance from the blood and reduced vasodilation


Various Pathogens-chlamydia pneumoniae-cytomegalovirus-heliobacter pylori

-these agents are hypothesised to inflame the endothelium thus permitting influx of LDL

-the exact role if any of pathogens in

atherosclerosis is yet to be worked on


-Nitric oxide-increased levels give vasodilation, antiplatelet effects


Genetics

-HDL- LCAT, CETP

-LDL- LDL receptor

-VLDL- LPL (apo C-II-activation, C-III) inhibition)

- -chylomicrons-LPL

Genetics

-Lp (a) – apo (a)

-cholesterol- HMG-CoA reductase

-platelets-cyclooxygenase and lipoxygenase

Genetics

-leptin (obesity)

Genetics

-immune response

adequacy of response in part governed genetically-possible implications include the infection/inflammatory issues mentioned above

Genetics

-nitric oxide synthase

-nitric oxide synthase gene polymorphisms affect level of this enzyme and hence nitric oxide levels

Documents

Note Midterm - 4 March in class