Digestion and Transport of

TAG by Plasma Lipoproteins

Chapter 18

Chapter 15

Lippincott’s Illustrated Review

Biochemistry

G

L

Y

C

E

R

O

L

FATTY ACID

FATTY ACID

FATTY ACID

TRIACYLGLYCEROL

G

L

Y

C

E

R

O

L

FATTY ACID

FATTY ACID

PHOSPHOACYLGLYCEROL

PHOSPHATE

ALCOHOL

Lipoproteins

• Multimolecular Complexes of Lipids

and Proteins

• For Transport of Lipids in the Plasma

• Lipids Include

– TAG Triacylglycerol

– CE Cholesterol Ester

– CH Cholesterol

– PL Phospholipids

Apolipoproteins

• The Protein Part of Lipoproteins

• Amphipathic

• Include Several Classes

Apo A, Apo B-48, Apo E.…

• Structural Role, Regulatory Role and

Binding to Cell Surface Receptors

Classes of LipoproteinsLipoprotein Density Protein Major Lipid

Chylomicrons

Composition

of Plasma

Lipoprotein

Lipoprotein Apo Protein Types

Chylomicrons Apo B, Apo C, Apo E

Dietary Lipids

VLDL Apo B, Apo C, Apo E

Endogenous TAG

IDL Apo B, Apo E

LDL Apo B Cholesterol

HDL Apo A, Apo C, Apo E

Cholesterol

Return to Liver

Digestion of Dietary Lipids

TAG + 2H2O 2 FA + MAG

CE + H2O FA + Cholesterol

Solubility Problem

Lipase

Colipase

MAG

FA

TAG

TAG

Cholesterol

Ester

,

Phospholipids

,

,

TAG

,

Fatty Acid

Monoacylglycerol

Cholesterol

Digestion of TAG with Short or

Medium Chain Fatty Acids

• Bigins in the Stomach

Lingual Lipase

Gastric Lipase

• Acid Stable

• Significance

– In Neonates

– In Pancreatic Insufficiency

Metabolism of SphingolipidsSphingophospholipids

Glycosphingolipids

Faisal Khatib MD; PhD

Faculty of Medicine, University

of Jordan

Sphingosine; Amino Alchol

Sphingosine; Amino Alchol

HO-CH-CH=CH-(CH2)12CH3

CH-NH2I

CH2-OH

Ceramide: Fatty Acid joined to

Sphingosine

HO-CH-CH=CH-(CH2)12CH3O║

CH-NH-C-(CH2)n-CH3ICH2-OH

2

Sphingomyelin is Phosphocholine

Ester of Ceramide

HO-CH-CH=CH-(CH2)12CH3O║

CH-NH-C-(CH2)n-CH3ICH2-O -CH2-CH2-N(CH3)3

+P

G

L

Y

C

E

R

O

L

FATTY ACID

FATTY ACID

PHOSPHOACYLGLYCEROL

PHOSPHATE

ALCOHOL

Sphingophospholipids

+ CO

Transfer Of Phosphocholine to Ceramide

Produces

Ceramide Phosphatidyl Choline

SphingomyleinDiacyl Glycerol

Sphingomylein

Glycolipids are Formed by Linking

one or More Sugars to Ceramide

Ceramide +

-Glucose or Galactose => Cerebroside

-Sulfated Galactose => Sulfoglycosphingolipids

-Oligosaccharide => Globoside

-Oligosaccharide with NANA => Gangliosides

N-Acetylneuraminic Acid (NANA)

Activated Donors in Glycolipids

Synthesis

• UDP-Glucose

• UDP-Galactose

• UDP-N-Acetylgalctoseamine

• CMP- N-Acetylneuraminic Acid

Galactocerbroside

Glucocerbroside

Transfer of Sulfate Group to Galactocerbroside Produces

Sulfogalatocerbroside (Sulfatide)

Degradation of Sphingolipids• Hydrolytic Enzymes, Specific for the Sugar

• - α Galactosidase

- β Galactosidase

- neuraminidase

- Hexoaminidase

• In Lysosomes

• Enzymes are firmly Bound to Lysosomal Membrane.

• The pH Optimum 3.5-5.5

• Stepwise Sequential Process

• “Last on, First off”

Glc Gal

Gal

GalNAcGal

NAcGal

NANA

NANA

NANA

Glc

Glc Gal

Glc Gal

βGalactosidase

βHexoseaminidase

neuraminidase

Sphingolipidoses

• Lipid Storage Diseases

• Defect in one of the Enzyme

• Accumalation of Specific Lipid

Substrate of the Defective Enzyme

Inherited as Autosomal RecessiveDisease

• Brain is Mostly Affected.

• Extent of Enzyme deficiency is the same in

Different Tissues.

Degradation of Sphingomyelin

Sphingomyelin

Ceramide

SphingosineSphingomyelinase

Ceramidase