Genetics of Dyslipidemia Flashcards
obesity, heart disease and type 2 diabetes all caused by (blank)
dysfunctional response to the hormone insulin
What is a messed up glucose test?
greater than 200
If you have elevated blood glucose you can bank on getting what?
B. A. N. K Heart disease and High BP Blindness amputation neuropathy kidney disease heart disease high blood pressure
If you have elevated blood lipid what might you get?
heart disease and stroke and high blood pressure
Complications/disease for type II diabetes is largely preventable if blood glucose and lipid levels are (blank)
KEPT IN CHECK
Both blood glucose and lipid levels are regulated by (blank)
insulin
If you have hyperglycemia then..
if you have hypoglycemia then….
diabetes
death
When do you see life threatening hypoglycemia?
when type I diabetics give themselves too much insulin
Insulin and glucagon secretion is stimulated by (blank or blank)
arginine or a protein meal
What are he four major forms of single gene causes of hypercholesterolemia?
LDLR loss of function mutations (AD)
APOB receptor binding site mutations (AD)
PCSK9 gain of function mutations (AD)
LDLRAP1 loss of function mutations (AR)
What is this:
elevated plant sterols, loss of function mutations in ABCG5 or ABCG8.
Rare, autosomal recessive. These ABC transporters preferentially pump plant sterols out of intestinal cells into the gut lumen and out of liver cells into the bile ducts
sitosterolemia
(blank) is an autosomal dominant disorder that causes severe elevations in total cholesterol and low-density lipoprotein cholesterol
Familial Hypercholesterolemia (FH)
(blank) is a transmembrane protein that is the primary pathway for the removal of cholesterol from circulation.
LDL receptor
(blank) internalizes LDL via endocytosis and allows for cholesterol to be released into the cell.
Where is this abundant?
LDLR
THe liver
LDL is bound to (blank) and brought into cell. It then goes into endosome and falls off of receptor because of the low ph of the endosome and this allows the receptor to be recycled out to bring more LDL in. The LDL that is left in the endosome is broken down.
APO B
LDLR mutations: Class 1? Class 2? Class 3? Class 4? Class 5?
1-> null alleles (no receptors) 2-> defective transport alleles creating mutated receptors 3-> defective binding alleles 4-> defective internalization allels 5-> defective recycling allels
When you have a class 2 LDLR mutation you have a defective transport allele creating mutated receptors. There are two subclasses of Class 2 LDLR muations. WHat are they and what do they do?
Class 2a: Complete blockage of transport of the receptor from the ER to the Golgi apparatus.
Class 2b: Partial blockade of transport of the receptor from the ER to the Golgi apparatus.
If you have an ApoB binding mutation then what is messed up?
the APOB itself,not the receptor
Explain a PCSK gain of function mutation
It is loss of ability to normally degrade LDL receptors i.e loss of LDL receptor homeostasis
Explain a LDLRAP1 loss of function mutation
autosomal recessive hypercholesteremia
LDL receptor adaptor-protein is broken so do no have proper LDL receptor binding to clatherin to be internalized. I.e you cant bring cholesterol into cell
What are these:
These drugs inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. They are designed to mainly inhibit the enzyme in the liver. Inhibition of cholesterol synthesis further decreases circulating LDL because reduced levels of cholesterol in the hepatocyte cause it to upregulate expression of LDL receptors.
statins
What are these:
These bind to the nuclear receptor PPAR-alpha. This receptor works as a transcription factor to alter gene expression in target cells. This increase HDL levels and decrease triglyceride levels.
Fibrates
What is these:
You may know of this as an essential nutrient of the vitamin B complex. At high doses (much higher than required for its role as a vitamin), This increases HDL levels and decreases triglyceride and LDL levels. The mechanism of action is not fully defined, but it appears to inhibit an enzyme in the liver that is involved in triacylglycerol synthesis, causing a decrease in VLDL production. Another effect in the liver is to prolong the half-life of HDL particles by preventing HDL breakdown. Recent work has also identified a specific receptor for this that may also play a role in mediating its action. This is the most effective drug for raising HDL levels.
Niacin
What is this:
This inhibits cholesterol absorption in the small intestine. This reduces absorption of dietary cholesterol, but also promotes cholesterol excretion, since biliary cholesterol accounts for some of the cholesterol that passes through the small intestine. THIs effectively lowers LDL cholesterol, however clinical trials have called into question whether further lowering cholesterol with this drug is truly beneficial in reducing atherosclerosis and heart disease.
ezetimibe
