20.1 Lipid digestion, absorption, and transport

lipids cellular roles

Structural, Energy storage, Minor fraction

Structural lipids

as membrane components, diacylglcyerol, glyerophospholipids

Energy storage lipids

fat droplets, triacylglycerol (TAGs)

Minor fraction lipids

used in signaling molecules (hormones, prostaglandin)

what do Very hydrophobic molecules in lipids need to be do first

be processed in order to be absorbed

90% of dietary lipids are what

TAGs and major form of metabolic energy reserve

what breaks down TAGs

lipases

what products are absorbed in the intestinal lumen

polar free fatty acid/mono-acyl glcyerol

what are Free fatty acids repackaged into

lipoproteins

what happens after Free fatty acids are repackaged into lipoproteins

transport lipids from the intestine to liver, for “on demand” release to other tissues

Sources of Fatty acid Fuels

consumed in diet, stored in cells as lipid droplets, synthesized in one organ for export to another, obtained by autophagy

where are Dietary Fats absorbed

small intestine

what enzyme hydrolyzes TAGs

Pancreatic lipase (triacylglycerol lipase)

what does lipase (triacylglycerol lipase) hydrolyzing TAGs form

1,2-diacylglycerols, 2-acyl-glycerols

Where is pancreatic lipase most active

lipid-water interface

What is interfacial activation

Increased enzyme activity due to a conformational change when pancreatic lipase binds at the lipid-water interface

What is required for pancreatic lipase to bind at the lipid-water interface

Mixed micelles of phosphatidylcholine (PC), bile acids, pancreatic colipase

bile acids

amphipathic cholesterol derivatives that act as detergents

What is the role of phosphatidylcholine (PC) in lipid digestion

Helps form mixed micelles for lipase activity

What determines the rate of TAG digestion

interface surface

how is the rate of TAG digestion greatly increased

churning peristaltic movements of the intestine and emulsifying action of bile acids

Substrate-free lipid

no lipid micelles, colipase, Lid close the active site

Substrate-bound lipid

with lipid micelles, Beta5, Lid open the active site

which lipases preferentially catalyze reactions at interfaces

phospholipase A₂

what does phospholipase A₂ do instead of changing its conformation

contains a hydrophobic channel that shelters the hydrophobic substrate as its extracted from the aggregate surface to the enzyme's active site

significant kinetic barrier

lipid substrate need not become solvated and then desolvated

what is The mixture of the more dispersed mono-/di-acylglycerols produced by lipases absorbed by

cells lining the small intestine (the intestinal mucosa)

Bile acids also function

help deliver FA to the intestinal surface

what must is the requirement for Long chain FA

kept soluble inside intestinal cells

what do FAs form complexes with

intestinal fatty acid-binding protein (I-FABP)

why do FAs form complexes with intestinal fatty acid-binding protein (I-FABP)

increase their effective water

what is Olestra

fat substitute made by acylating sucrose

Why does olestra mimic real fat

has a similar “mouthfeel” to triacylglycerols (TAGs)

Why can’t olestra be digested by intestinal lipases

too bulky for lipases to hydrolyze

Does olestra provide calories? Why or why not?

No, because no fatty acids are released or absorbed and have no calories

unpleasant side effects of olestra

Olestra droplets prevent partitioning of hydrophobic vitamins/nutrients into bile micelles, Stool composition

What is a current use of olestra

used as a lubricant in small power tools

how are lipids transported as

Lipoproteins

Why can’t free fatty acids travel freely in the bloodstream

too hydrophobic

What do intestinal mucosal cells do with absorbed fatty acids

Reconvert them into triacylglycerols (TAGs)

Why must TAGs be packaged for transport

poorly soluble in aqueous environments

chylomicrons

Lipoprotein complexes that transport dietary lipids

What is inside the core of a chylomicron

TAGs and cholesteryl esters

What surrounds the chylomicron core

amphiphilic layer of protein, phospholipids, cholesterol

function of the chylomicron outer layer

Allows the particle to be soluble in blood

Where are chylomicrons released after formation

Into the intestinal lymph

How do chylomicrons reach the bloodstream

Through lymphatic vessels that drain into larger veins

Where are chylomicrons delivered

To tissues like skeletal muscle or adipose tissue

What determines whether lipids go to muscle or adipose tissue

Energy needs vs excess (storage in adipose if excess)

what do the 5 classes of lipoproteins vary by

composition (payload), transport direction, function

classes of lipoproteins

Chylomicrons, Very low density, Intermediate density, Low density, High density

where are chylomicrons lipids from

dietary absorption in intestine

where are Very low density, Intermediate density, Low density lipoproteins from

liver to periphery tissue

where are high density lipoprotein from

periphery tissue to liver

VLDL/IDL/LDL feature

synthesized in liver to transport endogenous & repackaged dietary TAGS along w/ cholesterol from liver to periphery tissues

example of internally produced lipoprotein

lipogenesis

HDL feature

transports cholesterol and other lipids from peripheral tissues back to the liver

what is Each lipoprotein particle coated with

~20-Å-thick polar surface monolayer of protein, phospholipid; coating is more dense than TAG core

Lipoprotein particle densities relation with diameter

increased with decreasing diameter

why does Lipoprotein particle densities go UP w/ decreasing diameter

outer coating is more dense; HDL, which are the most dense of the lipoproteins, are also the smallest

what are Apolipoproteins

proteins in their lipid free form that bind lipids to form
lipoproteins

what do Apolipoproteins target

triacylglycerols, phospholipids, cholesterol, cholesteryl esters
for transport between organs

what ate Chylomicrons

particles consisting of triacylglycerols, cholesterol, apolipoproteins

what are Lipoprotein particles

spherical aggregates of apolipoproteins and lipids

Lipoprotein particles structure organization

arranged with hydrophobic lipids at the core and hydrophilic protein side chain and lipid head groups at the surface

Lipoprotein particles ranges

various in densities depending on combinations of lipid and proteins,from chylomicrons and VLDL to VHDL

what do Apolipoproteins coat

Lipoprotein Surfaces

what is the protein components of lipoproteins known as

apolipoproteins or apo- proteins

how many apolipoproteins are distributed in different amounts among human lipoproteins

9

what apolipoprotein does LDL contain

apolipoprotein B-100 (apoB-100)

what is apolipoprotein B-100 (apoB-100)

4536-amino acid monomer that covers at least half of the particle surface; hydrophobic face contacts core, polar face contacts solution

what are Helices in apolipoproteins

hydrophilic and hydrophobic side chains on opposite sides of helical cylinder (amphipathic) and float on phospholipid surfaces

Apolipoproteins not only package TAGs, what ekse do they do

tissue specific “delivery labels”

what is Apolipoprotein B-48 (apo B48)

Primary protein component of chylomicrons

what is Apolipoprotein C-II (apo C-II)

Protein picked up in the blood by chylomicrons from HDL particles

where do Chylomicrons adhere to

binding sites on endothelium inner surface of capillaries in skeletal muscle and adipose tissue

how are Chylomicron's TAG hydrolyzed

through the action of the extracellular enzyme lipoprotein lipase

what does Chylomicron's TAG being hydrolyzed do

allowing tissues to take up the liberated monoacylglycerol and free FA’

FA theme

dietary TAG to FA (cross intestine) → FA to TAG for delivery (intestinal
epithelia) → TAG to FA to cross targeted cell membrane

what happens to Chylomicrons as TAGs get hydrolyzed

shrinks, reduced to cholesterol-enriched remnants

whats the path of the. cholesterol-enriched remnants

dissociate from the capillary endothelium, re-enter circulation, & taken up by the liver

where do Chylomicrons deliver dietary TAG’s

to muscle and adipose tissue, and dietary cholesterol ends up mostly in the liver

how are VLDL degraded

by lipoprotein lipase in the capillaries of adipose tissue and muscle

Receptor-mediated endocytosis

general mechanism whereby cells take up large molecules, each through a corresponding specific receptor

Which receptor is responsible for LDL uptake

LDL receptor

what do LDL particles in blood are sequestered by LDL receptors bind to

apoB-100

where do LDL receptors cluster into

clathrin-coated pits, gathering cell-surface receptors destined for endocytosis

what do the clathrin-coated pits come from and form

invaginate from the plasma membrane to form clathrin-coated vesicles

what do clathrin-coated vesicles do after divesting themselves of their clathrin coats

vesicles fuse with endosome vesicles whose internal pH is ~5.0, triggering LDL particle dissociation from its receptor

what do LDL receptors do after the clathrin-coated vesicles fuse with endosome vesicles

recycled back to the cell surface, while the endosome with its enclosed LDL fuses with a lysosome

what happens to LDL's apoB-100 in the lysosome

rapidly degraded to its component AA’, cholesteryl esters are hydrolyzed to yield cholesterol and free FA’s

Receptor-Mediated Endocytosis of LDL step 1

apolipoprotein B-100 component of LDL specifically binds to LDL receptors on clathrin-coated pits

Receptor-Mediated Endocytosis of LDL step 2

clathrin coats depolymerize

Receptor-Mediated Endocytosis of LDL step 3

uncoated vesicles fuse with endosomes, LDL particles dissociates

Receptor-Mediated Endocytosis of LDL step 4

secondary lysosome hydrolyzes cholesteryl esters, releases cholesterol

Receptor-Mediated Endocytosis of LDL step 5

cholesterol is converted to cholesteryl esters and enter the ER

HDL function

removes cholesterol from the tissues

where are HDL assembled

in plasma from components obtained through the degradation of other lipoproteins

what does a circulating HDL particle

acquires its cholesterol by extracting it from cell-surface membranes, and converting to cholesteryl esters by the HDL-associated enzyme lecithincholesterol acyltransferase (LCAT)

what do HDL function as

cholesterol scavengers