Lipid digestion and inter-organ transport Russian National Research Medical University Maxim A. Abakumov Moscow, 2014

Lipid digestion and inter-organ transport

Russian National Research Medical University

Maxim A. Abakumov

Moscow, 2014

Lipids

• Large group of organic compounds

containing long hydrocarbon chains or rings

• Poorly sooluble in water

• Well soluble in organic solvents

• Usually large size molecules

Lipid functions

• Structural component of biological membranes• Energy storage• Hormones and vitamins• Lipophilic bile acids important for lipid

solubilization

Lipid classificationLipids

GlyceridesFatty acids

Saturated Unsaturated Neutralglycerides

Phosphoglycerides

Nonglyceride lipids Complex lipids

Waxes Sphingolipids Steroids Lipoproteins




Phosphoglycerides



Fatty acids

• Carboxylic acids with long (C8-C20)

hydrocarbon «tail»

• Saturated fatty acids contain only σ-bonds

(single bonds)

• Unsaturated fatty acids contain also π-bonds

(double bonds)

Fatty acids

Saturated fatty acids

• Have even number of carbon atoms

• Contain maximum hydrogen atoms

• Hydrocarbon chains (HC) are full length

straight

• Have high melting point

Unsaturated fatty acids

• Have even number of carbon atoms

• Contain less hydrogen atoms then saturated

FAs

• Each doble bond bent HC for 30°

• Have low melting point

Fatty acids

Trans- and cis-fatty acids

Oleic acid Elaidic acid

Cis double bond Trans double bond

Fatty acids nomenclature

Fatty acids

Essential fatty acids




Phosphoglycerides



Triglycerides

Phospholipids

X

R1

R2

O

O

O

O

CH

CH2

CH2

O

O

O-

O

P

X

X

Fattyacid chain

Glycerol Phosphate




Phosphoglycerides



Sphingolipids

CH3

OH

NH

OR

CH3

O

Sphingosine

R Sphingolipid

H Ceramide

Phosphocholine Sphyngomyelin

Sugar Glycosphingolipid

Glycolipids

Fat digestion• Most fat is presented as TGs• Low water solubility• Large size• Low accebility for enzymes

• Bile acids create fat emulsion• Size of fat drops decreases• Surface increases• Accebility for enzymes increases

• TGs are hydrolized• Lipase• Colipase•Micells are formed•Fatty acids are transported into cells

Fat digestion• Most fat is presented as TGs• Low water solubility• Large size• Low accebility for enzymes

• Bile acids create fat emulsion• Size of fat drops decreases• Surface increases• Accebility for enzymes increases

Fat emulsification• TGs are hydrophobic- solubilization is needed.• Key players – bile acids• Bile acids are cholesterol derivatives• Synthesized in liver from AcCoA• Amphiphilic molecules

OH

CH3

CH3

CH3

H

H

H

HCH3

CH3

Fat emulsification

Nonpolarregion

Polar(charged)region

Bilesalt

Emulsification

Fat droplets coated with bile salts are suspended in water

Bile acids

Primary bile acids

Synthesized in liver from cholesterol

Secondary bile acids

Bacteria in gut

Conjugated bile salts

• Occurs in liver• Both with primary and secondary bile acids• Glycine or taurin are conjugated• To carboxylic group on bile acid tale

O

NH2OH O

S

OOH

NH2

Glycine Taurine

Conjugated bile salts

Glycoholic acid Tauroholic acid

OH

O

OHOH

OHCH3

CH3

CH3

H

H

H

H

O

OHOH

OHCH3

CH3

CH3

H

H

H

HO

NHOH

O

OHOH

OHCH3

CH3

CH3

H

H

H

H O

S

OOH

NH

Cholic acid

Enterohepatic circulation of bile acids

Pancreatic lipase

• Hydrolyse TGs into 2 fatty acids and

monoacylglyceride

• Extracellular enzyme

• Secreted by pancreas

• Esterase enzyme subclass

Fat digestion

• TGs are hydrolized• Lipase• Colipase•Micells are formed•Fatty acids are transported into cells

Pancreatic lipase

Free fatty acids

Pancreatic lipase hydrolase bonds between glycerol and fatty acids at positions 1 and 3

Position 1

Position 3

Colipase

• Small protein• Cofactor for lipase• Prevent lipase inactivation by bile salts• Required for effecient lipase work in intestine• Secreted as procolipase (inactive)• Activated by trypsin

Colipase

Long chain TGs

• Long chain TGs (LCTG)– contain fatty acids with 14-22 carbon atoms

• Poor solubility in water• Requires bile acids for digestion and transport• Resinthesized in intestinal cells• Combined with lipoproteins to form chylomicrons • Transported in chylomicrons into lymphatic system• Can be stored in adipose tissue prior to oxidation in

liver

Long chain TGs

Medium chain TGs

• Medium chain TG (MCTG) – contain fatty acids with 8-10 carbon atoms

• Higher polarity, then LCTG• Bile acids are not required for absorbtion• Transported into blood in natural state• Faster oxidized in liver• Don’t go to adipose tissue

Medium chain TGs

Interorgan lipid transport

• Lipids are poorly soluble in water• Special lipoprotein complexes are used for lipis

solubilization• Each lipoprotein complex transport lipids in one

direction• Main directions are

1) Intestine→Liver

2) Liver→Peripheral organs

3) Peripheral organs

Interorgan lipid transport

Peripheral tissue

Chylomicrons

VLDL, LDL, IDL HDL

Lipoproteins in lipid transport

Lipoproteins

Lipoproteins in lipid transport

Chylomicrons

• Largest lipoprotein• Contains largest amount of lipids• Transport TGs from intestine to peripheral

tissue• Transport TGs and cholesterol to liver

(remnant chilomicrons)• Mostly dietary TGs• Main proteins are: B-48, A, C, E• Supresses cholesterol biosynthesysis

Chilomicrons

Very low density liporpotein

• VLDL• Mostly contain endogenous TGs and

cholesterol.• Synthesized in liver• Transport endogenous TGs from liver to

peripheral tissue• Main proteins are: B-100, C, E• Same metabolism as chilomicrons except

fact that VLDL are synthesized in liver

VLDL

Intermediate density lipoprotein

• IDL• Contain both endogenous TGs and

cholesterol esters (CE)• Transport TGs and CE to peripheral tissue• Synthesized from VLDL in blood stream by

lipoprotein lipase (LPL)• Main proteins are: B-100, E

Low density lipoprotein

• LDL

• Contain more CE then TG

• Transport CE from liver to peripheral tissue

• Synthesized from IDL (VLDL) in blood

stream

• Main proteins are: B-100

IDL and LDL

VLDL

LPL

Remnant VLDL(IDL)

Liver internalizationApoB-100

(LDL-receptor)

LPLHL

LDL

Liver internalizationApoB-100

(LDL-receptor)

Peripheral tissueApoB-100

(LDL-receptor) FA+cholesterol

FA to peripheral tissue

FA to peripheral tissue

Type DeficiencyLipid

elevated in blood

Lipoprotein elevated in

bloodComments

IFamilial

lipoprotein lipase(rare)

apoC-II (rare)

TriglycerideChylomicro

ns

Red-orange eruptive xanthomas, Fatty liver

Acute pancreatisAbdominal pain after fatty

meal

IIaFamilial

hypercholesterolemia

Cholesterol LDL

High risk of atherosclerosis and

coronary artery diseaseXanthomas of the Achilles

tendonXanthelasmasCorneal areus

High density lipoproteins

• HDL• Contains largest amount of CE, less TG• Transport cholesterol (CE) to liver from

peripheral tissues• Synthesized in liver and intestine as

Apolipoprotein A1• Main protein are: A1

High density lipoproteins

Documents

Lipid digestion and inter-organ transport Russian National Research Medical University Maxim A. Abakumov Moscow, 2014