Lipids Digestion & Absorption

ByDr. Walaa Bayoumie El Gazzar

Adult human ingests 60-150 gm of fats perday. 90% or more is normally triacylglycerol(TG) while the remainder consists ofcholesterol, cholesterol esters (CE),phospholipids, and non-esterified(unesterified) fatty acids (NEFA).

Dietary lipids:

DIEGESTION OF TRIACYLGLYCEROLS

• Lipases are enzymes that digest triacylglycerols. Fourlipases are present in the alimentary tract:

lingual, gastric, pancreatic and intestinal lipases.

The lingual lipase is secreted by the Ebner’sglands found on the dorsal surface of thetongue. It does not act in the mouth becauseof the very short time the food stays there.

The gastric lipase is secreted by the gastric chiefcells in the fundic mucosa in the stomach. In thestomach, some digestion of fat occurs by the lingualand gastric lipases. This appears to be ofphysiological significance in the infant since thegastric pH is much higher than in the adults(optimum pH for both lipases is 3-6) and the milk fatis highly emulsified, both conditions being requiredfor the action of the two enzymes. In addition, the 2enzymes are more specific for the primary esterlinkage with short and medium-chain fatty acids,especially at position 3, conditions that apply to milkfat.

In neonates, pancreatic production of lipase is not fully developed.

• Breast milk is rich in medium- and short-chain fatty acids that are adequatelyhandled by breast milk–derived lipase(carboxyl ester lipase) and infantilegastric lipase.

In contrast to formulas designed for term infants, prematureinfant formulas supply medium-chain triglycerides.

•Esters are formed by the reaction of alcohol and carboxylic acid (when

the carboxyl group of fatty acid combine with the hydroxyl group of

glycerol)

•sn-1 and sn-3 positions (or α-positions), sn-2 (or β-position)

• Gastric lipase, together with lingual lipase,comprise the two acidic lipases. These lipases,unlike alkaline lipases (such as pancreatic lipase),do not require bile acid or colipase of optimalenzymatic activity.

• Acidic lipases make up 30% oflipid hydrolysis occurring during digestion in thehuman adult, with gastric lipase contributing themost of the two acidic lipases. Thus theremainder of fat digestion is largely dependenton pancreatic lipase and the lowergastrointestinal tract.

In the small intestine:

• Emulsification (in digestion): The breakdown offat globules in the duodenum into tiny droplets,which increases the area of contact between thelipase enzyme and the lipid droplets, thusincreasing the rate of hydrolysis.

• Lipid emulsflcation occurs in the duodenum bythe churning effect of peristalsis, helped by thepresence of bile salts. Lipid emulsification is alsohelped by monoacylglycerols (result from thepartial hydrolysis of fats), by phospholipids andby lysophospholipids (result from the partialhydrolysis of phospholipids).

• Emulsification of fats is necessary for theirdegradation and absorption. Byaffecting emulsification process it is possible todecrease activity of lipolytic enzymes and thusdecrease fats’ absorption, which could be usefulin control of obesity and related diseases.

• An investigation on the effects of polyphenols onfats’ emulsification has shown that polyphenolsfrom green and black tea can increase size of lipiddroplets and decrease the specific area of contactwith enzymes.

The pancreatic lipase is specific for the primary esterlinkage (at the α-positions). It first removes the fatty acid inpositions 3, forming 1,2-diacylglycerol. It then removes thefatty acid in position 1, forming 2-monoacylglycerol.

• The fatty acid in position 2 cannot be hydrolyzed by lipase. Anisomerase enzyme may slowly transfer it to the 1 positionwhere it can be hydrolized by lipase. It may also be slowlyhydrolyzed by the enzyme cholesteryl esterase.

A primary alcohol is an alcohol which has the hydroxyl group connected toa primary carbon atom. It can also be defined as a molecule containing a“–CH2OH” group.

A primary carbon is a carbon atom which is bound to only one othercarbon atom.

Colipase is a protein secreted by the pancreas. It binds with the pancreaticlipase and helps it binding with the substrate.

Thus, of the ingested triacylglycerols:

22% are completely hydrolyzed into glycerol and 3 fatty acids;

72% are partially hydrolyzed into 2- monoacylglycerol (2-MAG) and 2 fatty acids; and

6% are partially hydrolyzed into 1-monoacylglycerol (1-MAG) and 2 fatty acids.

The intestinal lipase works within the intestinalmucosal cells, where it continues the hydrolysisof the absorbed 1-monoacylglycerols, formingglycerol and a fatty acid.

• PL may be absorbed without digestion withinthe micelles. They are also hydrolyzed by thepancreatic phospholipase A2 (requires ca2+

and bile salts for its activity)tolysophospholipids which help the process ofemulsification, digestion and absorption ofTAG.

Digestion of phospholipids:

ph

FA1

N base

FA2

• They are also hydrolyzed by the pancreaticenzyme cholesteryl esterase (needs bile saltsfor its activation) into cholesterol and a fattyacid.

The end product of digestion of lipids aremainly: 2-monoacylglycerol, 1-monoacylglycerol, glycerol, cholesterol,phospholipids, lysophospholipids and freefatty acids.

Digestion of cholesteryl esters:

Absorption of lipids

Glycerol and short & medium chain fatty acids

• These are water soluble, so they passdirectly from the intestinal lumen throughintestinal cells to the portal blood then to theliver. The latter contains an active glycerolkinase for utilization of glycerol.

• Glycerokinase is found in liver,kidney, intestine, and lactating mammarygland tissues.

formation of micelles:

The other products of the digestion of lipidsform with bile salts fine emulsified particleswhich are termed micelles. These micelles areessential for the process of absorption andtransport of lipids into the intestinal cells.

• Long chain FA will be activated first by thiokinase(acyl – CoA synthetase) forming acyl CoA whichis used for the reesterification of the absorbed 2-monoacylglycerols, forming triacylglycerols.

• Glucose, by glycolysis, gives dihydroxyacetonephosphate, which is reduced to glycerol 3-phosphate.

• Acyl-CoA is used for the esterification of glycerol3-phosphate, forming phosphatidic acid. Thephosphate of the latter is removed, forming I ,2-diacylglycerol, which is converted totriacylglycerol.

Phosphatidic acid

• Also, cholesterol united with active acylCoA by the aid of acyl CoA cholesterolacyl transferase (ACAT) to formcholesterol ester.

• Lysopholipids are reacylated to formphospholipids by a family ofacyltransferase.

• The triacylglycerols formed become associatedwith little cholesteryl ester. These becomesurrounded by a single layer of amphipathic lipids(phospholipid and cholesterol) and proteins (apoA and apo B-48), forming minute particles calledchylomicrons.

• Chylomicrons are released to the intercellularspace , then pass to lymphatic vessels drainingthe intestine (lacteals), then by the way ofthoracic duct, they reach the systemic circulation

• In abetalipoproteinemia, apo B-48 cannot beincorporated into chylomicrons. This causesaccumulation of triacylglycerols in intestinalepithelium together with defective absorptionof triacyiglycerols from the intestines, leadingto steatorrhea.

DEFECTS IN DIGESTION AND ABSORPTION OF LIPIDS

• Steatorrhea, or fatty diarrhea, is the appearance of excessiveamounts of lipids (>6 g/day) in stools. It leads to loss of weightas well as deficiency of essential fatty acids and the fat-soluble vitamins A, D, E and K. It may be caused by:

A. DEFICIENCY OF PANCREATIC LIPASE:

• This occurs in chronic pancreatitis, cystic fibrosis, obstructionof the pancreatic duct by tumors, and after pancreatectomy.In addition, in severe hyperacidity the pH in the intestinesbecomes unsuitable for the activity of pancreatic lipase. Inthese cases the lipid of feces is mostly in the form ofundigested triacyiglycerol.

B. DEFICIENCY OF BILE SALTS

This occurs in tumors or stones of the bileduct, and in some cases of hepatitis and livercirrhosis. The lipid of the stools is digested. Inaddition, in cases of bile duct obstruction, thefeces acquire a light color due to the lack ofbile pigments and serum bilirubin is elevated.

C. DEFECT IN INTESTINAL EPITIIELIUM

• These include the malabsorption syndromes.There is degeneration of intestinal villi, leadingto failure of fat absorption. Fecal lipid isdigested, also CHO & proteins are notabsorbed