lipid digestion and absorption

what do epithelial cells contribute in terms of endogenous lipids?

2-6 g/day membrane lipids from epithelial cells

what percent of dietary lipids are phospholipids (come from cell membranes)?

5% (4-6 g each day)

of the fat we consume, what percent of it is triglycerides?

90% (main constitute of vegetable oils and animal fats)

what is the ideal intake of fat? (what percent of our energy should come from fat?)

<70g of fat (<30% of our energy) typical adult western diet has 100g of fat (~40% of the energy comes from fat)

hepatic uptake of chylomicron remnants is mediated by:

Apo-E

fat digestion that starts in the stomach is completed by the proximal small intestine, predominantly by enzymes synthesized and secreted by pancreatic cells. fatty acids in the stomach trigger the release of:

CCK

when you add lipids in small amounts to water, what happens?

the polar lipids form stable or unstable monolayers on the surface of the water

what happens when you add lipids in bulk to water?

their behavior varies from insolubility (triglycerides and cholesterol) to the formation of macroaggregates (bilayers and micelles)

what effect do lipases have on triglycerides?

they release a single fatty acid from the triglyceride, leaving behind diglycerdies

where do the endogenous lipids come from

bile and desquamated intestinal epithelial cells and dead bacteria

Because Apo-B28 lacks the carboxy-terminal domain of Apo-B100 it is unable to:

bind to the LDL receptor (like Apo-B100 can)

how do micelles get transported?

bulk phase in alkaline region, diffuse across to acidic zone where sodium hydrogen antiporter contributes to acidic environment and fatty acids are ionized. fatty acids get absorbed from microvilli of enterocytes along small intestine

what is the role of LPL (lipoprotein lipase) in circulation?

catalyzes release of free fatty acids from chylomicron triglycerides and converts them into triglyceride-poor cholesterol-enriched chylomicron remnants

chylomicrons have the highest percent of triglyceride of any of the lipoproteins. chylomicrons have less TG because they have:

cholesterol (60% TG, 20% cholesterol) compared to 5% TG in chylomicrons as you move from VLDL to IDL to LDL there is more cholesterol and less TG until you get to HDL! because HDL has phospholipids and it transfers most of its cholesterol back to LDL

what happens in you are deficient in LPL?

chylomicronemia; over 100 LPL gene mutations that have been identified loss of LPL in mice is lethal; overexpression of LPL is beneficial

apolipoprotein C has two forms (Apo-CII and Apo-CIII) what is the role of Apo-CII

cofactor for LPL and enhances the enzyme's activity

what are skin lipids?

come from diet chemically diverse and complex and difficult to digest

why might overexpression of LPL be beneficial?

decreases plasma triglycerides increases fatty acid uptake in muscle protects against HF-feeding-induced obesity note: insulin-resistant humand have less active LPL that contributes to elevated plasma TGs

how do you treat abetalipoproteinemia?

dieting involving lots of vitamin E

what must happen before lipids can be digested and absorbed?

emulsification of fine oil droplets in water

what is the role of GPIHBP1?

endothelial cell protein that transports LPL from the subendothelial spaces to the capillary lumen (LPL comes in from adipocytes, myocytes, and macrophages and then endothelial cells bring it in)

what is a triglyceride?

ester derived from glycerol and three fatty acids

lipovitamins and provitamins are present in:

fat (may also contain lipid-soluble toxins and carcinogens from the environment)

how is hepatic lipase different from LPL?

it doesn't require Apo-CII to function it's made in the liver

what does pancreatic lipase do?

it hydrolyzes the ester bonds of triglycerides at the 1st and 3rd position forming 2 fatty acids and 1 monoacylglyceride

what happens when Apo-CIII (3) levels are high?

it inactivates LPL so humans with genetic mutation in Apo-CIII have a more favorable lipid profile compared to those with normal levels

what are the main endogenous lipids?

lecithin and cholesterol and membrane lipids + lipid from dead bacteria

what are the 2 major lipases?

lingual and gastric

what is the origin of VLDL?

liver

where is the full length Apo-B100 made?

liver!

what is the origin of HDL?

liver, intestine plasma

muscle lipoprotein lipase has a ________ Km than the adipose tissue LPL to ensure cardiac muscle has first preference for triglycerides

lower

increased surface area to volume ratio (after chewing, gastric turning, and intestinal peristalsis of lipids) increases the area of the oil-water interface. what keeps the dispersed lipid particles from coalescing?

the emulsion droplets are coated with membrane lipids, denatured proteins, dietary polysaccharides, certain products of digestion (fatty acids and monoglycerides), biliary phospholipids and cholesterol (the core of the droplet is triglyceride with cholesterol esters and other nonpolar or weakly polar lipids)

a single missense mutation in GPIHBP1, G56R, causes:

severe type 5 hyperlipoproteinemia=fasting chylomicronemia

Most phospholipids are glycerophospholipids. the other major class of membrane phospholipid is:

sphingolipid (has a sphingosine rather than a glycerol backbone)

what is the role of CCK?

stimulate flow of bile into duodenum and secrete pancreation of enzymes

why are long chain fatty acids not absorbed by the stomach?

the carboxyl groups are protonated and insoluble at pH 4, so they don't get absorbed in the stomach, but rather stay in the core of the lipid droplet

what is the predominant type of dietary lipid?

triglycerides

a lipase found in human milk (bile salt stimulated milk lipase is important for fat digestion in breast fed infants. milk lipase is stable during passage in the acid pH of the stomach and is active against:

triglycerides, diglycerides, monoglycerides, cholesterol esters, and foat-soluble vitamin esters

what activates pancreatic procolipase?

trypsin (cleaves pro-colipase into colipase and enterostatin)

how does the liver take up chylomicron remnants?

via Apo-E occurs via LDL receptor and LDL receptor related protein (LRP)

what is a lipase?

water-soluble enzyme that catalyzes hydrolysis of ester chemical bonds in water-insoluble lipid substrates

how much free or unesterified cholesterol is found in the diet?

~0.5 g

how do we emulsify dietary fats?

(after chewing/etc): 1. long chain fatty acids and other products of lipid digestion are converted to triglycerides, phospholipids, and cholesterol esters in the SER. 2. fat droplets form in the cisternae of the SER 3. apoproteins are synthesized in the RER and then transferred to the SER where the apoproteins associate with lipid droplets 4. chlyomicrons and VLDLs come to the cis side of the Golgi apparatus and apoproteins are glycosylated 5. vesicles carrying chylomicrons or VLDLs bud off from the trans golgi and move to the basolateral membrane in transport vesicles 6. transport vesicles fuse with basolateral membrane and release chylomicrons or VLDLs 7. chylomicrons and VLDLs pass through the interendothelial channels of lymphatic capillaries and enter the lymph 8. glycerol, short chain, and medium chain fatty acids pass through the enterocyte and enter the blood capillary

in adult humans, what is secreted in the duodenum in its *active* form in 1000-fold excess.

*pancreatic lipase (NOTE: NOT infants)*

what properties of lipases make them efficient and hydrolyzing ester chemical bonds in lipids in the stomach?

1. they have an acidic pH optima 2. they are stable in acidic environments (the stomach) 3. the are resistant to digestion by pepsin 4. they are not inhibited by emulsifiers on lipid droplets

what types of lipids can come from the diet?

1. triglycerides 2. phospholipids: glycerophospholipids (phosphatidylcholine) and sphingolipids 3. cholesterol (unesterified and esterified) 4. lipovitamins/provitamins 5. skin lipids

what does bile contribute in terms of endogenous lipids?

10-15g/day of lecithin 1-2 g/day unesterified cholesterol WAY more (2-4x) than you get in the diet

what do bacteria contribute in terms of endogenous lipid?

10g/day of lipid comes from dead bacteria and is added to the colon

in healthy adults, what percent of fat digestion occurs in the stomach?

15%

what secretes lingual lipase?

Ebner's glands on dorsal side of tongue

what does Apo-E bind to?

HSPG (heparan sulfate proteoglycan) secretion/capture hypothesis

what is the origin of LDL?

IDL

what is the "bad" cholesterol and why?

LDL because it is high in cholesterol

Apo-B100 is the ligand for what receptor?

LDL receptor

lipoprotein lipase is differentially regulated in muscle and adipose tissue. what happens to LPL in adipocytes and myocytes in the fasted state?

LPL synthesis decreases in adipocytes LPL synthesis increases in myocytes

lipoprotein lipase is differentially regulated in muscle and adipose tissue. what happens to LPL in adipocytes and myocytes in the fed state?

LPL synthesis increases in adipocytes LPL synthesis decreases in myocytes

what is the origin of IDL?

VLDL

Apo-B100 serves at the structural protein for:

VLDL, IDL, and LDL

what produces LPL (lipoprotein lipase)?

adipoctes, myocytes in skeletal and cardiac muscle, and macrophages it gets transported to the surface of capillary endothelial cells of these tissues

what is free or unesterified cholesterol derived from?

animal membranes

where are lipids in the diet derived from?

animals and/or plants (composed of carbon, hydrogen, and a smaller amount of oxygen) some lipids have small amounts of nitrogen and phosphorous too

Why might we need lipase in human milk?

because infants don't have pancreatic lipase, so bile-salt-stimulated milk lipase is important for fat digestion in breast-fed infants

why can medium and short chain fatty acids be absorbed in the stomach,unlike long chain fatty acids?

because they are mainly ionized and soluble at pH 4 and are able to be passively absorbed across the gastric mucosa into portal blood

what stimulates CCK to be secretion?

fatty acids generated in the stomach

what is esterified cholesterol derived from?

food made from blood products or liver

what reduces the size of lipid droplets and increases the ratio of surface area to volume?

food preparation, chewing, and gastric turning. intestinal peristalsis (segmental contraction) mixes luminal contents with pancreatic and biliary secretions

what begins the emulsification of fats?

food preparation, chewing, and gastric turning. intestinal peristalsis (segmental contraction) mixes luminal contents with pancreatic and biliary secretions together, these processes reduce the size of lipid droplets and increase the ratio of surface area to volume

what secretes gastric lipase

gastric chief cells

most phospholipids are a type of:

glycerophospholipid

what does phospholipase act against?

glycerophospholipids from which is releases 1 fatty acid to give you lysophospholipids

what makes Apo-E?

hepatocytes in the liver; it gets secreted and exists in the extracellular space around hepatocytes in high concentration

is colipase secreted in an active or inactive form?

inactive (lipase is secreted in active form)

what is one symptoms of chylomicronemia (LPL deficiency)?

increased serum triglycerides and xanthomas=fat deposits under the skin

in healthy adults 15% of fat digestion occurs in the stomach. how is that different in infants? why?

infants have a lot more fat absorption in the stomach because they consume mostly milk fat which is medium to short chain fatty acid, which can be absorbed in the stomach

what is the origin of chylomicrons?

intestine

where is apoB-48 (truncated form of apolipoprotein B100) made?

intestine; via posttranscriptional C-->U RNA editing of nuclear transcript that introduces a translational stop codon, resulting in a protein encoding the amino terminal 48% of apoB-100

what is MTP?

microsomal triglyceride transfer protein; it transfer triglycerides, cholesterol esters, and phospholipids to chylomicrons and VLDL particles. more than 12 mutations of MTP interfere with its activity

3 enzymes require bile, what are they?

milk lipase carboxyl ester hydrolase phospholipase A2

emulsion droplets eventually break down to:

mixed micelles

what is a lipid?

nonpolar, polar, or amphiphilic (both hydrophobic and hydrophilic)

where is pancreatic lipase active?

only at oil-water interface of emulsion droplets however! surface emulfiers inhibit lipase, so you need colipase

what are the 4 key pancreatic enzymes involved in lipid digestion?

pancreatic lipase colipase carboxyl ester hydrolase phospholipase A2

what is the function of colipase?

pancreatic lipase works at oil-water interface of emulsion droplets, but there are surface emulsifiers there that inhibit lipase. colipase reverses that inhibition by either attaching and serving as an anchor or forming a complex with the lipase that binds to the lipid interface

what can inactivate acidic lipases?

pancreatic proteases (small intestine)

what is the most predominant dietary phospholipid?

phosphatidylcholine (lecithin)

what is abetalipoproteinemia

rare autosomal recessive disorder caused by deficiency in MTP, which results in virtual absence of apo-B lipoproteins in plasma (can't transfer TGs, cholesterol esters and phospholipids to chylomicron and VLDL particles) results in malabsorption of fat and fat-soluble vitamins from the intestine