Transfer of Lipids from One Compartment to Another

Putative transport/transfer proteins:

PC-TP

GLTP

StAR

NPC1

Lipid movement into and out of cells

Why do lipids need transporters?

Enterohepatic circulation

Made in ER of intestinal and liver cells

Made at surface of cells with appropriate receptors by remodeling VLDLs and chylomicrons

Apoprotein - MW (Da) Lipoprotein Association Function and Comments

apoA-I - 29,016 Chylomicrons, HDLmajor protein of HDL, activates lecithin:cholesterol acyltransferase, LCAT

apoA-II - 17,400 Chylomicrons, HDLprimarily in HDL, enhances hepatic lipase activity

apoA-IV - 46,000 Chylomicrons and HDLpresent in triacylglycerol rich lipoproteins

apoB-48 - 241,000 Chylomicrons

exclusively found in chylomicrons, derived from apoB-100 gene by RNA editing in intestinal epithelium; lacks the LDL receptor-binding domain of apoB-100

apoB-100 - 513,000 VLDL, IDL and LDLmajor protein of LDL, binds to LDL receptor; one of the longest known proteins in humans

apoC-I - 7,600Chylomicrons, VLDL, IDL

and HDLmay also activate LCAT

apoC-II - 8, 916Chylomicrons, VLDL, IDL

and HDLactivates lipoprotein lipase

apoC-III - 8,750pChylomicrons, VLDL, IDL

and HDLinhibits lipoprotein lipase

apoD, 33,000 HDL closely associated with LCAT

cholesterol ester transfer protein, CETP HDLexclusively associated with HDL, cholesteryl ester transfer

apoE - 34,000 (at least 3 alleles [E2, E3,

E4] each of which have multiple isoforms)Chylomicron remnants,

VLDL, IDL and HDLbinds to LDL receptor, apoE-4 allele amplification

associated with late-onset Alzheimer's disease

apoH - 50,000 (also known as -2-glycoprotein I)

Chylomicrons triacylglycerol metabolism

apo(a) - at least 19 different alleles; protein ranges in size from 300,000 - 800,000

LDL

disulfide bonded to apoB-100, forms a complex with LDL identified as lipoprotein(a), Lp(a); strongly resembles plasminogen; may deliver cholesterol to sites of vascular injury, high risk association with premature coronary artery disease and stroke

LCAT= lecithin cholesterol acyl tranferase

CEPT = cholesteryl-ester transfer protein

SR-BI = scavenger receptor, BI

So why are LDLs “bad” and HDLs “good”?

The anti-IgG will recognize the half of IgM molecule that does not undergo type switching during maturation. Because antibodies are bivalent, they can cross-link the cell surface immunoglobulins by binding a different cell surface IgM molecule to each of the two antigen binding sites. The cell responds, in turn, by redistributing the cross-linked cell surface immunoglobulins.

(a) What are the distribution patterns of IgM on normal and antibody-treated cells.(b) What changes in distribution require metabolic energy from the cell, and what changes occur passively and are due only to the cross-linking. Metabolism is inhibited either by treatment with sodium azide or by incubation at 4oC. By treating cells with fixative before adding the fluorescent antibody, you can determine what the normal, unperturbed immunoglobulin localization is.

control

cold

hot

Hot az

Cold azide

Treatment 1 (immediate fixing with fixative): produces ring staining

Treatment 2 (no treatment with chemicals; on ice): produces predominantly patching

Treatment 3 (sodium azide on ice): produces predominantly patching

Treatment 4 (no treatment with chemicals; 37°C): produces capping

Treatment 5 (sodium azide at 37°C): produces predominantly patching

Put down that jelly doughnut and look carefully at this aorta. The white arrow denotes the most prominent fatty streak in the photo, but there are other fatty streaks scattered over the aortic surface. Fatty streaks are the earliest lesions seen with atherosclerosis in arteries.

                           

Atherectomy