Week 9: Lipids

dietary lipids are absorbed in the __________

intestine

in the exogenous pathway, chylomicrons are sent to the _________

liver

what are fatty acids?

linear chains of C-H bonds terminating in carboxyl group

what are triglycerides?

3 fatty acid molecules attached to 1 glycerol by ester bonds

phospholipids are similar to triglycerdies except with ___________ fatty acids

2 esterified

the third position on the glycerol backbone of phospholipids contains what?

phospholipid head

types of head groups on phospholipids

• choline

• inositol

• serine

• ethanolamine

• all hydrophilic

structure of cholesterol

• unsaturated steroid alcohol

• 4 rings

• single side chain tail

cholesterol is almost exclusively synthesized by ___________, not readily ___________ by cells, and not a source of ______

animals, catabolized, fuel

structure of lipoproteins

• usually spherical

• 10-1,200 nm

• made of lipids and proteins

______________ deliver fuel to peripheral cells

lipoproteins

_____________ are the largest lipoproteins and the least dense, up to 1200 nm

chylomicrons

chylomicrons are produced by the ____________ and deliver dietary lipids to ___________ and ___________ cells

intestine, hepatic, peripheral

VLDLs (very low density lipoproteins) are produced by the ________, and are the major carriers of endogenous _____________

liver, triglycerides

______ form as a result of lipolysis of VLDL

LDL

LDL is readily taken up by cells via receptors in _________ and __________ cells

liver, peripheral

________ are significantly smaller than VLDLs and can infiltrate extracellular space

LDLs

______________ are LDL-like particles that are varying in size and density

lipoprotein (a)

plasma levels of ______ vary widely among individuals in a population, but stay constand within a person

Lp(a)

______ are the smallest and most dense, made by the ______ and __________

HDLs, liver, intestine

HDLs can be ______-shaped or _________-

disk, spherical

HDLs are capable of removing excess ____________ from peripheral cells

cholesterol

______ can be separated into 13-14 subfractions

HDLs

lipids and lipoproteins are ____________ in water

insoluble

what are the primary lipids?

• cholesterol

• triglycerides

• lipoproteins

  • chylomicrons

  • LDL

  • HDL

• phospholipids

• fatty acids

exogenous lipid metabolism (digestion)

• pancreas/small intestine

• LPS + triglycerides → free fatty acids + glycerol

• cholesterol esterase + cholesterol → free cholesterol + free fatty acids

• chylomicrons are made

endogenous triglycerides are made by the _________ from glycerol and fatty acids

triglycerides

endogenous triglycerides are transported as ________

VLDL

what enzyme hydrolyzes VLDL → LDL?

lipoprotein lipase (LPL)

LDL is cholesterol ______

rich

free cholesterol is synthesized from __________

acetyl CoA

bile acid breaks down ___________

cholesterol

90% of cholesterol is ____________, 10% is ____________

synthesized, dietary

LCAT

• lecithin-cholesterol acyltransferase

• made in liver

• turns free cholesterol → cholesteryl ester

  • transfers a fatty acid

ACAT

• acyl-cholesterol acyltransferase

• also turns free cholesterol → cholesteryl ester

  • transfers a fatty acid

LCAT is found in ________, ACAT is found in ________

blood, cells

_____ of cholesterol is free, ______ of cholesterol is esterified

1/3, 2/3

increased free cholesterol ____________ HMG-CoA reductase (rate-limiting step)

inhibits

cholesterol-lowering drugs block cholesterol synthesis by inhibiting what enzyme?

HMG-CoA reductase

LDL transports cholesterol…

to the cells

HDL transports cholesterol…

from the cells to the liver

_____________ is excreted in bile, and is also used in steroid hormone synthesis

cholesterol

apolipoproteins are proteins that bind _________

lipids

apolipoproteins form ____________ to help transport lipids

lipoproteins

there are _____ types of apolipoproteins

5

apolipoproteins are a _________ on a lipid-protein molecule

protein

apolipoprotein a is a major protein on _____

HDL

what is described?

• least dense lipoprotein

• transports exogenous triglycerides

• normally not in fasting serum

• plasma appearance

chylomicrons

VLDL is associated with which apolipoprotein?

Apo B

VLDL transports _____________ triglycerides

endogenous

VLDL is produced by the _________

liver

the liver produces which lipids?

• lipoproteins

  • HDL

  • VLDL

• triglycerides

• cholesterol

• phospholipids

_____ = “bad” cholesterol

LDL

is LDL or HDL described?

• Apo B

• transports cholesterol to peripheral cells

• binds to receptors on cells

• increased risk of atherosclerosis

LDL

_____ = “good” cholesterol

HDL

is LDL or HDL described?

• ApoA

• transports excess cholesterol from peripheral cells to liver

• decreases risk of atherosclerosis

HDL

lipoprotein (a)

• LDL-like molecules containing an extra apolipoprotein

• thought to increase risk of CHD

• genetic

most LDL lowering drugs don’t lower _____

Lp(a)

which lipoprotein is described by its components?

• 90% TG

• 5% cholesterol

• 4% phospholipid

• 1% protein

chylomicrons

which lipoprotein is described by its components?

• 65% TG

• 15% cholesterol

• 10% phospholipid

• 10% protein

VLDL

which lipoprotein is described by its components?

• 35% phospholipid

• 25% cholesterol

• 20% TG

• 20% protein

IDL

which lipoprotein is described by its components?

• 50% cholesterol

• 25% phospholipid

• 20% protein

• 5% TG

LDL

which lipoprotein is described by its components?

• 55% protein

• 25% phospholipid

• 20% cholesterol

• 5% TG

HDL

dyslipidemias can be __________ or _____________

genetic, acquired

diagnosis of hyperlipoproteinemias

• initial increased TG and/or cholesterol

• repeat with 12 hr fast specimen

• xanthomas

• primary or secondary disorder?

xanthoma

• localized, non cancerous, buildup of lipid-laden macrophages (foam cells)

• yellow-orange bumps under skin

what can cause primary hypertriglyceridemia?

• inherited chylomicron with VLDL clearance defect

• decreased LPL activity (cannot break down VLDL)

what can cause secondary hypertriglyceridemia?

• dietary

• hypothyroidism

• DM

• nephrotic syndrome

• obstructive liver disease

what condition do these lab findings indicate?

• increased chylomicrons, VLDL, or both

hypertriglyceridemia

what can cause hypercholesterolemia with LDL?

• familial hypercholesterolemia

  • decreased LDL receptor # / activity

• many secondary conditions

decreased LDL receptor # / activity causes what to occur?

• increased atherosclerosis and CAD risk

• markedly elevated total cholesterol and LDL

what can cause hypercholesterolemia with HDL?

familial hyperalphalipoproteinemia

what lab findings are seen with familial hyperalphalipoproteinemia?

• increased HDL

• slightly increased total cholesterol

• decreased CAD risk

combined hyperlipidemia

• most common inherited lipid disorder

• increased total cholesterol and TGs

• low HDL

• familial high cholesterol and CHD

  • DM, alcohol, hypothyroidism adds to problem

_______________________ is a primary hypolipoproteinemia

hypoalphalipoproteinemia

what lab findings are seen with hypoalphalipoproteinemia?

decreased total cholesterol and HDL

tangier disease

• rare genetic disorder

• deficiency or lack of HDL and apoA-I

• decreased apoA synthesis

• increased cholesterol esters → orange-yellow tonsils

• increased CAD risk

tangier disease is an example of what?

hypoalphalipoproteinemia

what lab findings are seen with hypobetalipoproteinemia?

• decreased total cholesterol and LDL

• decreased apo B synthesis

what conditions can cause secondary hypolipoproteinemias?

• hyperthyroidism

• liver parenchymal diseases

  • destroys liver cells → cirrhosis

how does hypothyroidism affect lipid levels?

causes unfavorable shift in blood lipids, increasing total cholesterol, LDL, TGs, and lip(a)

total cholesterol method

• coupled enzyme

• CE, CO, and peroxidase enzymes

• oxidized chromogen produced and measured

cholesterol esterase reaction

cholesterol esters → free cholesterol + fatty acids

cholesterol oxidase reaction

cholesterol + O2 → cholestenone + H2O2

HDL-cholesterol methods

• selective lipoprotein precipitation

• homogenous (direct) HDL

selective lipoprotein precipitation

• reagent

  • divalent cations in buffer, heparin, or dextran

• lipoproteins with apo B precipitate

  • HDL in supernatant

• centrifuge → measure HDL

what interferes with selective lipoprotein precipitation?

• elevated TG

• correct with dilution

homogenous (direct) HDL method

• no manual separation

• selective inhibition of non-HDL lipoproteins

  • uses total cholesterol agent

does TG interfere with homogenous (direct) HDL methods?

no

LDL-cholesterol methods

• friedewald calculation

• analytical methods

  • selective lipoprotein precipitation

  • immunoseparation

what is the friedewald calculation?

LDL-C = total cholesterol - HDL - (TG/5)

the friedewald calculation is only valid when TG < _________

400 mg/dL

when the LDL/HDL ratio is ____________, there is an increased CAD risk

increased

other lipoprotein methods

• 4C overnight EDTA plasma appearance

• lipoprotein separation

4C overnight EDTA plasma appearance

• creamy top layer → increased chylomicrons

• turbidity → increased VLDL

• yellow-orange → increased LDL

lipoprotein separation method can be used in what situations?

when TG > 400 mg/dL OR there is suspected abnormal lipoproteins present

how can lipoprotein separation be performed?

• electrophoresis and a lipid stain

• ultracentrifugation

  • relative density

triglyceride method

• coupled enzyme

• LPS, GK, G6PD enzymes

• NADH measured

desirable range for total cholesterol

< 200 mg/dL

desirable range for HDL-cholesterol

• males: > 37 mg/dL

• females: > 40 mg/dL