Generation of Energy from Dietary Lipids
what does the pancreas secrete to aid in digestion of long chain fatty acids?
**bicarbonate--neutralize pH **pancreatic/Triacylglycerol lipase's --digest
Arachidonic acid (AA) is an essentail__________
*20 carbons precursor to a number of important biological compounds known as *eicosanoids*
Secretin (THINK pH)
*In response to the low pH in the chyme entering intestine------> secretin is released and causes the pancreas to secrete bicarbonate to neutralize the pH of the intestinal contents
Vitamin D what if you don't have enough??
*Osteomalacia (inadequate bone mineralization) *Rickets in children
glycolipids
*contain a ceramide +carbohydrate group (either a galactose or a glucose)
sphingomyelin
*contains ceramide +phosphocholine or phosphoethanolamine
Most fatty acids are...
*even # of carbons *most common: 16- and 18- carbon FA *unsaturated *cis
Vitamin D other name? where is it found? function?
calciferol *found in dairy & sun * absorption of Ca2+ and phosphorous from intestines and deposition into bones
who induces the synthesis of LPL (lipoprotein lipase)?
insulin!
major site for digestion of long chain fatty acids?
intestines (duodenum) *Bile salts break up large fat droplets into smaller micelles, increasing the surface area for digestive enzymes.
Phosphatidylcholine what if you don't produce it!?
is a common phospholipid and is also called a glycerolphospholipid or a phosphoacylglycerol Acute respiratory distress syndrome (ARDS) is a disease related to maturity of the fetal lung, and accounts for 15-20% neonatal mortality in Western countries. Proteins, phospholipids, and phosphatidylcholine (80%) make up lung surfactant. The level of PC rises at 35 wk of gestation in the amniotic fluid. PC coats alveoli of lungs and reduces surface tension, preventing lung collapse. The lack of surfactant in babies born prematurely would lead to ARDS.
unsaturated the more unsaturated it is the ________ the melting point
the more unsaturated the fatty acid is the LOWER the melting point *check out the "designation" omega 3's in green!!--
explain option 3 further Resin STOPS RECYLing "ion-exchange resins can bind to bile salts and prevent the recycling back into the liver (EXample--cholestyramine) "
well... CHOLESTRYRAIMINE cholesterol is converted to bile salts! if you can't reabsorb bile salts...your body must make more!! (elimination cycle)
Plasmalogen role?
*form a significant fraction of the membranes in nervous tissue EXAMPLE: Platelet activating factor (PAF): extracellular mediator in the process of *inflammation *has antihypertensive activity *increases vascular permeability
phospholipids can be further broken down to..
*glygerophospholipids & *sphingolipids
CCK
*inhibits gastric motility *sends +POSITIVE+ signals to gallbladder to release bile *send +POSITIVE+ signals to the pancreas to release gastric enzymes
diets that are MUFA enriched have shown...
*lower cholesterol *lower TG *improve insulin resistance *provide anti-thrombotic affects
eicosanoid medications leads to..
*prostaglandins (the inflammatory hormones that aspirin interferes with) *leukotrienes are produced in the body from AA by the (enzyme 5-lipoxygenas)
Name the basic lipids found in an animal cell membrane?
*short chain fatty acids *medium chain fatty acids *MUFA *cholesterol *cholesterol ester! (when you add a fatty acid to polar cholesterol) *triglyerides *triglyerides with/ MUFA *phospholipids
phospholipases
*take fatty acids 1 @ a time
what happens if you can't make chylomicrons? GENETIC DEFECT
*trouble with LCFA digestion *leads to severe neural degeneration treatment-vitamin E
how much bile salt gets synthesized? how much get secreted?
0.2-0.6 synthesized 0.2-0.6 secreted
Monounsaturated fatty acids
1 double
from cholesterol --->bile acids **3 testable items to remember**
1- the 1st step (hydroxylation) is limiting!! (7alpha-hydroxylase) 2- there are 2 bile acids to remember chenocholic acid (2 OH groups) & cholic acid (3 OH groups) 3-this process can be negatively regulated by chenocholic acid or cholic acid
Chylomicrons
1-carry TG that we have put back together to the *capillaries* 2-fats get release via lipoprotein lipase 3-chylomicron remnant goes back to the live with some TG still attached
purpose of micelles
1-emulsification 2- make products of lipid digestion more soluble *hydrophilic end together outside *hydrophobic end together inside *help bring partially digested fat into the cells
How can be lower cholesterol?
1-inhibit synthesis (statin drugs) 2-inhibit cholesterol from getting absorbed 3-ion-exchange resins can bind to bile salts and prevent the recycling back into the liver (EXample--cholestyramine)
Summary of fat digestion
1. The liver produces bile acids. 2. Dietary lipids are emulsified by bile acids in the duodenum. 3. The pancreas produces triacylglycerol lipase, colipase, bicarbonate, cholesteryl esterase, and phospholipases. 4. Triacylglycerol lipase (in complex with colipase) breaks down triacylglycerols in the emulsified fat droplet; this occurs at the surface of the fat droplet; other lipid-digesting enzymes also work at the surface of the emulsified fat droplet. 5. The products of triacylglycerol digestion, such as monoacylglycerols (MG) & fatty acids (FA), are solubilized in small bile salt micelles. 6. The MGs and FAs are absorbed into the intestinal epithelial cells from the bile acid micelles. 7. Chylomicrons are formed inside the cell. 8. Chylomicrons are transported out to 9. lymphatic and then enter blood. 10. Products of digestion in small micelles are shuttled over to the brush border.
lipids of physiological importance for humans (4)
1. They serve as structural components of biological membranes. 2. They provide energy reserves, predominantly in the form of triacylglycerols. *3. Both lipids and lipid derivatives serve as vitamins and hormones* *4. Lipophilic bile acids aid in lipid solubilization*
Vitamine K What if you dont have enough?
bruising easily bleeding disorders
western diet ratio of omega 6: omega 3?
15:1 (should be 2:1)
palmitic acid
16C!! saturated!
glycerolipids 2-MG (monoacylglycerol) POLAR
2 exposed -OH groups makes it polar!
Vitamine K other name? where is it found? function?
2 types--plant origin (Phytonadione) animal origin (Menaquinone) *found in bacterial flora of intestine, meat, green leafies! *function--blood clotting
The Enterohepatic Circulation how much bile salt is recycled?
95% of biliary secretion (3-5grams) *5% excreted
The Enterohepatic Circulation
=recycling of bile acids *active and passive transport* Humans cannot break down and metabolize cholesterol's complex ring structure (the "sterol ring") for energy. Therefore.... *the rings must either be *recycled* or *eliminated* This circulation of bile acids and salts occurs from the liver to the ileum of small intestine where digestion of fats takes place, and back to the liver.
Bile acid synthesis Defect! symptoms
A deficiency of hydroxylase enzyme involved in bile acid synthesis PROBLEM WITH THE PATHWAY (cholesterol--->bile salt) Symptoms: *progressive liver disease *cholestasis (accumulation of bile acid intermediate in the liver) *jaundice *liver fibrosis *abnormal bile acid precursor in urine (b/c you excrete some of it)
majority of bile salt get reabsorbed actively OR passively?
ACTIVE! in the ileum
the activity of LPL (lipoprotein lipase) depends on____________
ApoCII (on mature chylomicron)
POLAR--AMPHIPATHIC further broken down...
BOTH membrane lipids BUT... phospholipids & glycolipids (doesn't quite sit in the membrane)
Where are palmitic acids found?
BUTTER (saturated)
what is the livers major role?
Bile salts are produced in the liver, and bile is recycled back to the liver!
2 hormones that control lipid digestion
CCK Secretin
4 major categories of glycolipids (FYI)
Cerebrosides: contain a single moiety, principally galactose Sulfatides: sulfuric acid esters of galactocerebrosides. Globosides: contain 2 or more sugars. Gangliosides: similar to globosides except also contain sialic acid
Fat soluble vitamins (4)
DAKE D A K E **digested in the same way as fats! if you have an issue with fat absorption you may also have a vitamin deficiency
there are actually 3 omega 3 fatty acids!!!
EPA & DHA are made from Linolenic
what drug keeps cholesterol from being absorbed?
Ezetimibe
the more unstaturated vs. saturated fats you have determines_________about the membrane?
FLUIDITY
glycerophospholipids always have ....
Fatty acid 1 Fatty acid 2 Phosphate & and Alcohol (POLAR end)
When there are no double bonds... (saturated) the longer the chain the ____________ the melting point
HIGHER the melting point *check out the "designation" *** no double bonds on the fatty acids in this list
Trans
Hydrogens on the opposite side
CIS
Hydrogens on the same plane *easier to break
LPL is a ______________ enzyme (think insulin)
INDUCIBLE **works with insulin w/ LPL through process called induction!
what happens **if you attach a fatty acid** to POLAR cholesterol?
It becomes nonpolar known as cholesteryl ester!
Essential Fatty Acids
LA=Linoleic & ALA=Linolenic acid
ambient temperature unsaturated fatty acids are
LIQUIDS why? because of cis conformation **bonds cause a curved configuration and prevents packing into crystal form.
what does triacylglycerol lipase (from the pancreas) produce?
MGs & FA the products of triacylglycerol digestion,such as 1---glycerophospholipids 2-MG (monoacylglycerol)******REMEMBER WHEN YOU REMOVE 2 Fatty acids 2--- fatty acids (FA) (are solubilized in small bile salt micelles)
whats inside that micelle?
Mixed micelles are smaller and contain products of digestion: *FA (free) *lyso-phosholipids *2-MG cholesterol * fat-soluble vitamins * small amounts of bile salts micelles bud off from the large lipid droplet after digestion and move toward the brush border membrane of intestinal mucosal cells where the lipids are absorbed.
There are two general classes of lipids
Neutral (non-polar) NO CHARGE & Amphipathic lipids, (part polar)*some solubility*
secondary bile acids
OH removed by gut bacteria 1-deoxycholic acid 2-lithocholic acid
Where are oleic and lenolei acids found?
OLIVE OIL
Triacylglycerol Lipase AKA Pancreatic Lipase
Pancreatic lipase specifically cuts ester bonds at primary alcohols of TG (1 & 3 position shown here). The major products: 2-Monoacylglycerol & fatty acids
formation of chylomicrons
RER make the ApoB48 SER repackages the digested lipids they come together @ the golgi apparatus where they are packaged into chylomicrons and released lymphatics---->blood
Vitamin A other name? where is it found? function?
Retinol *found in orange foods *vision, growth, differentiation, & reporduction
Sphingophospholipids:
Sphingolipids are important components of the myelin sheath, a *multilayered* membranous structure that protects and insulates the nerve fibers. * Sphingomeylin is the primary sphingolipid in human* 80% lipids 20% proteins
IF you don't have a glycerol backbone you have a..
Sphinogosine
fat enter the body in _______ state BUTTT gets to the absorptive cells in ______ state
TG!!! triglycerides and triglycerides! HOWEVER from when it entered to when is reached cells for absorption is was broken down AND resembled
Gastric Lipase
TG=FA+ DG + MG (make up long chain fatty acids that get emulsified) short & medium chain fatty acids are sent to hepatic portal blood then carried by serum *albumin* to the liver
what happens if you eat too many fat soluble vitamins?
TOXIC!
how are MGS and FAs absorbed?
The MGs and FAs are absorbed into the intestinal epithelial cells from the bile acid micelles.
Vitamin E other name? where is it found? function?
Tocopherol *vegetable oil, nuts, & green leafy vegetables *Antioxidant
Linolenic acid (ALA)
Two important ω-3 fatty acids: EPA, eicosapentaenoic acid (20:5Δ 5,8,11,14,17), & DHA, docasahexaenoic acid (22:6Δ 4,7,10,13,16,19,), are metabolic derivatives of ALA and necessary for synthesis of a number of regulatory compounds in the body. ALA-→EPA, DHA. *EPA & DHA may reduce the risk of a heart attack. Fish oil contains DHA & EPA*
precursor to cholesterol
acetyl CoA
Bile acids what do they do?
aid is digesting fat! Bile acids/salts have a spatial configuration that gives them a polar "side" and a non-polar "side" **Emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets.
terminology from COOH group end
alpha, beta The carboxyl end (C-2 = α, C-3 = β)
Arcadonic acid +phospholipids =
arachidonate
linoleic (omega 6 (18-12=6) can make what?
arachidonic acid (another omega 6)!
long chain fatty acids require__________
bile salts for emulsications
Colipase
bile salts inhibit lipase **Colipase binds lipase anchoring it at the lipid aqueous phase, bringing it in contact with the oil droplet; & orienting the enzyme's active site toward its substrate. Lipase activity is increased by binding to the colipase.
Which one is better for you trans fats or saturated fats?
both stink! *same effect on health! *both promotes LDL increase *decrease HLD *increase TG LOWERING amount in your diet LOWERS risk for cardiovascular disease & obesity
primary bile acids
cholic acids & chenodeoxycholic acid
Plasmalogens what class of proteins? structure?
class of glycerolphospholipid *A long chain alcohol group in place of one FA
why is margarine JUST as bad for you as butter?
companies wanted to use vegetable oil for health but didn't want to lose shelf-life!! solution=margine they divided the cis unsaturated fatty acids to between trans and and cis! trans made it more solid!!!! but remember TRANS and SATURATED fatty acids are just as equally bad for you!
BUT we don't ingest fatty acids...!?
correct! we eat TG (triglycerides) & cholesterol! we have SO many different types of fatty acids...imagine the possibilities!
Fed stat LPL is _______ in the muscular tissue
decreased
cholesteryl esterase
degrades cholestryl esters to cholesterol + 1 FA. *Cholesterol esterase activity is increased in the presence of bile salts
Bile acids? who makes them? where are they made?
derivates from cholesterol **made in the liver peroxisome **made by by the cytochrome P450-mediated oxidation of cholesterol
Prior to secretion bile acids are conjugated with....
either glycine or taurine! why?? increases water solubility (change pK) and prevents passive reabsorption once secreted into small intestine note--hydrophobic face and the hydrophilic face note--pancreatic lipase coming in to digest the TG inside
chylomicrons must MATURE!? how do they do this?
in the plasma....HDL gives them A, E and C II
conjugated bile acids--->salts
glycine or taurine
omega 6 PUPFA_________ inflammation
increase! PROINFLAMMATORY
Fed state LPL is _______ in the adipose tissue
increased
LCFA when/where do we put the TG back together?
in the epithelial cells! **then the go and get package into the chylomicron
3 omega PUFA _______ inflammation
inhibit
cholesterol what makes is polar
it's a very hydrophobic molecule. the hydroxyl group makes it polar!
what is the mouth & stomach role?
lingual lipases- mouth gastric lipases- stomach **digest short and medium chain fatty acids --->MORE in the stomach only in the mouth for a few seconds
LPL where is it found? what does it do?
lipoprotein lipase found on the capillary wall *the chylomicron binds to this... break down it's contents into... FA & GLYCEROL (different then pancreatic lipases) **chylomicron remnants return to liver
Glycerol form LPL break down goes where?
liver!
Fatty Acids (FAs)
long chain of hydrocarbons w/ a carboxyl group @ 1 end molecule is defined by..... * the number of hydrocarbons *degree of unsaturation
LCFA before chylomicrons reach the blood where do they go?
lymphatics!
how is bile acid delivered?
made in the liver!! delivered through the gallbladder **The bile salts surround and emulsify dietary lipids in the duodenum. Meanwhile..... the pancreas produces bicarbonate to neutralize stomach acids, enzymes and co-enzymes, such as triacylglycerol lipase, colipase, cholesteryl esterase, and phospholipases.
chylomicrons structure
major protein in chylomicrons *Apo B48* requires phospholipids picks up apoA, apoC and apoE in the plasma
MUFA and PUFA contribute to the membrane fluidity
mono-unsaturated fatty acids poly-unsaturated fatty acids
Polyunsaturated fatty acids
more than 1 double bond
FA from the LPL break down goes where?
muscle & adipose tissue
Vitamin A what if you don't have enough??
nightblindness xerophthalmeia (dryness)
oleic acid vs. stearic acid
oleic acid has one C=C double bond and is therefore considered an unsaturated fatty acid (USFA) oleci=1 kink UNSATURATED
2 essentil fatty acids
omega 3 & omega 6 linoleic (omega 6 (18-12=6) linolenic acids (omega 3 (18-15=3) **our bodies cannot synthesize them!
terminology from methyl group end
or from the methyl end (ω-1 is the methyl carbon). omega 1, omega 2, omega 3
Bile acid synthesis Defect! treatment?
oral bile acid therapy causing suppression of 7a-hydroxylase and preventing further synthesis of cholestatic intermediates
Vitamin E What if you dont have enough?
rare...may cause hemolytic anemia
eicosanoids
regulate body functions, such as.... *immune function *blood clotting *blood pressure
Lipid digestion in the duodenum
relatively large emulsified lipid droplets become coated with bile salts. ------>contains mostly TGs, cholesterol, CE, PLs, and fat-soluble vitamins. Digestive enzymes work at the oil-water interface to release free fatty acids (FFA) and 2-MG at the surface This allows molecules at the surface to pinch off into small microdroplets, called micelles. Micelles carry the products of digestion to the microvilli where they are absorbed into the intestinal epithelial cells
what is the Pancreas's role in digestion again?
releases enzymes *Lipase* and *Colipase* to assist lipase for digestion of Long chain fatty acids, and *bicarbonate* for pH neutralization. *assist lipase (triacylglycerol lipase AKA pancreatic lipase) * --->colipase is required to help *bicarbonate *phospholipases *cholesteryl esterase
essential fatty acid deficiency
reversible **The cow's milk is not recommended for infants < 12 months old because it contains mostly SCFAs & MCFAs and NOT the LCFAs (palmitic, oleic, or linoleic acids) which are most important for brain development in the first year. LC-PUFAs play a vital role in overall development of immunity in infants.
Classifying fatty acids by length (4)
short medium long very long
length determines what?
solubility in water
Sphingophospholipids
sphingosine backbone rather then a glycerol backbone *major component of nervous tissue and biological membranes
Ceramide
sphingosine with a fatty acid joined to its amino group
remember SCFA & MCFA dont need chylomicrons why?
thanks to gastric and lingual lipases!! they directly enter the portal blood and are transported to the liver bound to serum albumin
MUFA are found...
• Plant Oils: Canola oil, flaxseed oil, olive oil, peanut oil, pesto sauce, safflower oil, sesame oil, soybean oil, sunflower oil, walnut oil • Meat fat (pork, beef) • Nuts & seeds: Almonds, Brazil nuts, natural peanut butter, dry-roasted cashews, dry-roasted peanuts, dry-roasted sunflower seeds, hazelnuts, macadamia nuts, pecans, pine nuts, pistachios, roasted pumpkin seeds, sunflower seeds, walnuts • Avocado • Olives • Dark chocolate
