Chapter 8

Metabolism of lipid

Cai danzhao

Lipids are substances that are insoluble in water but soluble in organic solvents.

Including:

Fats (triglycerides ， triacylglycerols ， TAG)

Function: store and supply energy

phospholipids

Lipoids cholesterol and cholesterol ester

glycolipids

Function: as membrane compounds

Triglyceride(TAG) Phospholipid(PL)

Fatty acid Cholesterol (ch)

Cholesterol ester (CE)

Carboxyl

Saturated FA unsaturated FA (one double bonds)

Hydrocarbon chain

Nomenclature:

the chain length

number of double bonds

Palmitic acid 16:0

Oleic acid 18:1(Δ9)

Section 8.1

Digestion and Absorption of Lipids

Digestion of Lipids

Location: duodenum, small intestine

Condition:

1. bile salts (emulsification)

2. lipolytic enzymes

Pancreatic lipase

Phospholipase A2

Cholesterol esterase

Process bile salts

food lipids small particles

pancreatic lipase

triglyceride 2-monoacylglycerol + 2FFA phospholipase A2

phospholipid lysophosphatide + FFA cholesterol esterase

cholesterol ester cholesterol + FFA

Pancreatic colipasePancreatic colipse is the necessary cofactor of pancreatic lipase.

Excreted by pancreatic acinar cells as a proenzyme, which activated in the small intestine.

Can anchor the lipase to the surface of lipid micelles.

Assist lipase in two ways:

1.enhances the lipase activity

2.against the inhibitory effects of bile salts and surface denaturation.

Absorption of lipidsMedium and short chain fatty acid (10Cs or

less) TAG emulsification absorption intestine mucosal cells degradation FFA and glycerol transport portal vein

blood circulation

Long chain fatty acids (12-26C) + monoacylglycerol

absorbed synthesis

epithelial cells TAG

+ lipoproteins

lysophosphatide + FFA CM

absorbed synthesis (chylomicron)

epithelial cells PL

cholesterol + FFA lymphatic system

absorbed synthesis

epithelial cells CE blood circulation

CoA + CoA + RCOOH RCOOH RCORCOCoA CoA Acyl CoA synthetase

ATP ATP AMP PPiAMP PPi

CHCH22OH OH

CHCH22OH OH

CHOCHO--CC--RR1 1

O =

CHCH22OH OH

CHCH22OH OH

CHOCHO--CC--RR1 1

O =

CHCH22OH OH

CHCH22OO--CC--RR22

CHOCHO--CC--RR1 1

O=

O =CHCH22OH OH

CHCH22OO--CC--RR22

CHOCHO--CC--RR1 1

O=

O =CHCH22OO--CC--RR3 3

CHCH22OO--CC--RR2 2

CHOCHO--CC--RR1 1 O=

O=

O=

Acyl CoAtransferase

CoA R2COCoA R3COCoA CoA

Acyl CoAtransferase

TAG synthesis in epithelial cells: monoacylglycerol pathway

1,2-diacylglycerol TAGmonoacylglycerol

Section 8.2

Metabolism of Triacylglycerols

Degradation of TAG

FA

glycerol

Lipolysis: also named fat mobilization, is a

process breaking down the fat (TAG) stored in adipose tissue and liberating the glycerol and FFAs from which into the blood circulation.Key enzyme:

TAG lipase (hormone sensitive lipase, HSL)

Lipolytic hormones: stimulate TAG hydrolysis

Glucagons, Adrenocorticotropic hormone (ATCH) epinephrine norepinephrine

Anti-lipolytic hormones: stimulate TAG formation

insulin

prostaglandin E2

nicotinic acid

H2O FA H2O FA H2O FA

TAG DAG MAG Glycerol

TAG lipase a DAG lipase MAG lipase

TAG lipase a ADP + Pi TAG lipase b ATP

cAMP dependent protein kinase

ATP cAMP 5’-AMP Adenylate cyclase Phosphodiesterase

lipolytic hormones (Epinephrine )

anti-lipolytic hormones (insulin)

FFA +plasma albumins fatty acid- transport albumin complexes all the body

glycerokinaseGlycerol glycerol-3-phosphate

dihydroxyacetone phosphate

glucose metabolism

Notation: adipose cells and skeletal muscles lack glycerokinase, can not use glycerol well

β-Oxidation of Fatty acids

FAs are the major energy source of human

the biologically available energy in TAGs:

~ 95 % in their 3 long-chain FAs

~ 5% in their glycerol

Oxidation location: in the cytoplasm and mitochondria of

most body cells (except those of the brain and intestine)

The process of FA degradation

Activation

Transport into mitochondria

β-oxidation

Acetyl CoA utilization

into citric acid cycle

change to ketone bodies

into other metabolic pathway

1.Activation of FA

Activation of FA takes place on the outer mitochondrial membrane (in cytoplasm)

Acyl CoA synthase

+ + CoA-SH CoA-SH

脂 肪 酸RCHRCH22CHCH22CC--OH OH

OO=OO=

脂 酰~SCoA

RCHRCH22CHCH22CC~SCoA ~SCoA OO=OO=

Fatty acid Acyl-CoA

ATP AMP+PPiATP AMP+PPi

2.Transport of Acyl CoA into mitochondria

translocase

key enzyme: carnitine acyltransferase I

3. β-oxidation of Acyl CoA

In mitochondrial matrix, successive 2-C units are removed from the carboxyl end of the fatty acyl chain in the form of acetyl-CoA by a repeated sequence of 4 reactions, and the oxidation process take place at the β-carbon.

To Palmitoyl CoA (C16):

1.Dehydrogenation

(FAD)

2.Hydration

3.Dehydrogenation

(NAD+)

4.Thiolysis

Result of a round of β-oxidation :

1NADH, 1FADH2, 1Acytyl CoA, 1Acyl CoA (Cn-2)

C16 Acetyl -CoA

Acyl CoA (Cn-2) can now go through another set of β-oxidation reactions

1

2

3

4

5

6

7

1 molecule of palmitoyl-CoA will pass through the sequence 7 times, eventually be oxidized to: 8 Acetyl CoAs 7 NADHs 7 FADH2s

ATP produced during oxidation of palmitate

Activation of palmitate (C16) -2 ATP

β-oxidation:

8×10=80 ATP

7×2.5= 17.5ATP

7×1.5=10.5 ATP

8 Acetyl CoAs (enter TAC cycle)

7 NADHs

7 FADH2s

Total 106 ATP

2.67 Glucose (C16): 85.3 ATP

Alternative Oxidation Pathway of Fatty Acids

1.Unsaturated FA oleic acid (18:1, Δ9) :Can produce a cis-Δ3 C12 acyl CoA, but β-oxidation acts only on trans double bonds.

Enoyl-CoA isomerase: make a trans- Δ 2 C12 acyl CoA, then β-oxidation can continue

2,4-dienoyl-CoA reductase

Can convert cis- Δ 4 double bond

to trans- Δ 3,

Acyl-CoA oxidase

（ FAD ）

2.Peroxisomal Fatty Acid Oxidationfor very long chain FA digestion.(C20、 C22)

No ATP produced.

FA reduced in length by this pathway will be transferred to mitochondria for further oxidation.

very long chain FA(C20 、 C22)

（ peroxisomal ）

chain

shorted FA

（ mitochondri

a ） βOxidation

3.Propionyl CoA

β-oxidation of the odd-chain fatty acids, which are relatively rare in nature, produce a propionyl CoA in the final round.

CH3CH2CO~CoA Succinyl CoAcarboxylase

Citric acid cycle

Ketone Bodies Formation and Utilization

Ketone Bodies are

acetoacetate (30%)

β-hydroxybutyrate (70%)

acetone

Generated in liver cells (mitochondria), used by extrahepatic tissues (mitochondria also).

Precursor:

Acetyl CoA

CO2

CoASH

CoASH

NAD+ NADH+H+

HMGCoA synthase

CHCH33CSCoA CSCoA

==OOCHCH33CSCoA CSCoA

==OO==OO CHCH33CSCoA CSCoA

==OOCHCH33CSCoA CSCoA

==OO==OO

CHCH33CCHCCH22CSCoA CSCoA ((乙酰乙酰乙酰乙酰CoACoA))

==OO ==OOCHCH33CCHCCH22CSCoA CSCoA

((乙酰乙酰乙酰乙酰CoACoA))

==OO==OO ==OO==OO

HOCCHHOCCH22CCHCCH22CSCoACSCoA((HMGCoAHMGCoA) ) CHCH33

OHOH

羟甲基戊二酸单酰羟甲基戊二酸单酰CoACoA==OO ==OO

HOCCHHOCCH22CCHCCH22CSCoACSCoA((HMGCoAHMGCoA) ) CHCH33

OHOH

羟甲基戊二酸单酰羟甲基戊二酸单酰CoACoA==OO==OO ==OO==OO

CHCH33CHCHCHCH22COOH COOH D(D(--))--ββ --羟丁酸羟丁酸

OHOHCHCH33CHCHCHCH22COOH COOH

D(D(--))--ββ --羟丁酸羟丁酸CHCH33CHCHCHCH22COOH COOH

D(D(--))--ββ --羟丁酸羟丁酸

OHOH

CHCH33CCHCCH22COH COH 乙酰乙酸乙酰乙酸

==OO==OOCHCH33CCHCCH22COH COH

乙酰乙酸乙酰乙酸

==OOCHCH33CCHCCH22COH COH

乙酰乙酸乙酰乙酸CHCH33CCHCCH22COH COH

乙酰乙酸乙酰乙酸

==OO==OO==OO==OO

acetoacetateβ-hydroxybutyrate

3-hydroxy-3-methylglutaryl CoA

Acetoacetyl CoA

CHCH33CCHCCH3 3 丙酮丙酮

==OOCHCH33CCHCCH3 3

丙酮丙酮CHCH33CCHCCH3 3

丙酮丙酮

==OO==OO

acetone

Ketogenesis

Utilization of ketone bodies(cardiac, kidney, brain, skeletal muscles)

NAD+

NADH+H+

Succinyl CoA

succinate

CoASH+ATP

PPi+AMP

CoASH

CHCH33CHCHCHCH22COOH COOH D(D(--))--ββ --羟丁酸羟丁酸

OHOHCHCH33CHCHCHCH22COOH COOH

D(D(--))--ββ --羟丁酸羟丁酸CHCH33CHCHCHCH22COOH COOH

D(D(--))--ββ --羟丁酸羟丁酸

OHOH

CHCH33CCHCCH22COH COH 乙酰乙酸乙酰乙酸

==OO==OOCHCH33CCHCCH22COH COH

乙酰乙酸乙酰乙酸

==OOCHCH33CCHCCH22COH COH

乙酰乙酸乙酰乙酸CHCH33CCHCCH22COH COH

乙酰乙酸乙酰乙酸

==OO==OO==OO==OO

CHCH33CCHCCH22CSCoA CSCoA ((乙酰乙酰乙酰乙酰CoACoA))

==OO ==OOCHCH33CCHCCH22CSCoA CSCoA

((乙酰乙酰乙酰乙酰CoACoA))

==OO==OO ==OO==OO

CHCH33CSCoA CSCoA

==OO2 CHCH33CSCoA CSCoA

==OOCHCH33CSCoA CSCoA

==OO==OO2

β-hydroxybutyrate

acetoacetate

Acetoacetyl CoA

Physiological significance of ketogenesis

A way by which liver transfer fuel to extrahepatic tissues (prolonged starvation), ketone bodies can replace glucose as the major source of energy, especially for brain.

The normal concentration of ketone bodies in blood is very low.

﹤0.5mmol/L

Under starveling condition, ketogenesis is accelerated.

Under some pathological condition (such as diabetes), the synthesis is faster than utilization, so the concentration of ketone bodies in the blood is high, (up to 20mmol/L), which is called ketonemia ,

if the concentration is too high to be excreted in the urine, that is ketonuria.

Ketone bodies are acidic compounds, the accumulate of which in the blood will decrease the pH of blood , cause ketoacidosis.

FA oxidation ketogenesis

lipolysislipolytic hormones(glucagon)

Regulation of ketogenesis

1.Feeding status:

hungry state:

FFA FA oxidation

ketogenesis

Feeding state

insulin lipolysis FFA

2.Metabolism of glycogen in the hepatic cells

Sufficient glucose supply:

FFA triacylglycerols

Glucose deficiency:

FFA β- Oxidation ketogenesis

3.Malonyl CoA concentration

Malonyl CoA can inhibit carnitine acyltransferase Ⅰ.

malonyl CoA

transportion of fatty acids into mitochondria

β- Oxidation and ketogenesis

8.2.2 FA BiosynthesisFA synthesis is not the reverse of degradation:

different pathways, enzymes, location of cells

Location of FA synthesis:

cytoplasm of liver (major), adipose and other tissue cells.

First step: synthesis of palmitic acid

Palmitic Acid BiosynthesisMaterial:

acetyl CoA (come mostly from glucose)

NADPH (pentose phosphate pathway or produced by malate enzyme.)

ATP

HCO3-

Acetyl CoA must be transport to cytosol.

citrate citrate

oxaloacetate

malate

pyruvatepyruvate

oxaloacetate

Acetyl CoA ATP Acetyl CoA

MITOCHONDRIA CYTOSOL

Citrate synthase

ATP-citrate lyase

Inner membrane citrate pyruvate cycle

Formation of malonyl CoA

ATP + Acetyl CoA + HCO2- Malonyl CoA + ADP + Pi

acetyl CoA carboxylase

biotin act as CO2 carrier

Acetyl CoA carboxylase is the key enzyme of the FA synthesis.

Allosteric regulation:

up-regulate: citrate and isocitrate

down-regulate: palmitoyl CoA

Phosphorylation regulation

up-regulate: dephosphorylation

(insulin)

down-regulate: phosphorylation

(glucogen)

Repetivity steps catalyzed by Fatty Acid Synthase

The chain of FA grows 2-carbons per cycle.

The reactions are similar to the reversal of FA β-oxidation.

CH3COSCoA +7 HOOCH2COSCoA + 14NADPH+H+

CH3(CH2)14COOH +7 CO2 + 6H2O + 8HSCoA + 14NADP+

Fatty Acid Synthase

In mammalian:

Fatty acid synthase (Type synthaseⅠ ) is a single multifunctional polypeptide with 7 activities.

In E.coli (becteria): Fatty acid synthase system (Type Ⅱsystem) contain 7 enzymes organized into a cluster.

The acyl carrier protein (ACP) carries a growing fatty acyl chainfrom one active site to the next.

Process :

1.Charging β-ketoacyl-ACP synthase (KS) with an acetyl group

2.Charging ACP with a malonyl group

1

A. Addition of an activated acyl group with CH2-carbon of malonyl CoA,

3. 4 reactions add 2-cabon

B. Reduction of the β-keto group to an alcohol

1

C. Dehydration to create a double bond

D. Reduction of the double bond to create saturated fatty acyl group

4. The next round of 4-reactions

butyryl group transfers to (KS)

K

S

S

O=C

CH3

A

C

P

S

C=O

CH2—COO-

K

S

S

O=C

CH2

CH2

CH2

CH2

CH3

A

C

P

S

C=O

CH2—COO-

K

S

S

O=C

CH2

CH2

CH2

CH2

CH2

CH2

CH3

A

C

P

S

C=O

CH2—COO-

O-

O=C

CH2

CH2

CH2

CH2

CH2

CH2

CH3

CH2

CH2

CH2

CH2

CH2

CH2

CH2

CH2

K

S

A

C

P

HS HS

+

4H++4e-

CO2

K

S

S

O=C

CH2

CH2

CH3

A

C

P

S

C=O

CH2—COO-

4H++4e-

CO2

4H++4e-

CO2

a new round of reactions begin, till a 16-C saturated palmitate synthesized.

Elongation of FA Carbon Chain

In endoplasmic reticulum

elongate the chain by 2-C each time, the reactions is similar to what happened in palmitic synthesis, but no ACP is involved.

Material: Acyl CoA, malonyl CoA, NADPH

Product: C18 stearate (main)—C24 FA

In mitochondria

the process here is the reversal of β-oxidation, add 2-C each time.

Material: Acyl CoA, Acetyl CoA, NADPH,

NADH

Product:

C18 stearate (main)—C24 or C26 FA

Synthesis of polyunsaturated FAHumans have Δ4 、 Δ5 、 Δ8 、 Δ9 desaturase, can produce palmitoleic acid (16:1 Δ9) and oleic acid (18:1 Δ9) from palmitate and stearate.

NAD+

e- + [Cyt b5-Fe2+]

+ NADH + H+

Essential Fatty Acids (EFA)

linoleic acid (18:2 Δ9,12),

linolenic acid (18:3 Δ9,12,15)

arachidonic acid (20:4 Δ5,8,11,14)

must be obtained from dietary sources, usually from plant, called essential fatty acids.

reasons: there are no desaturases in human can produce double bonds beyond 9-10 carbon position.

Biosynthesis of triacylglycerols

Location: all tissues, intestine and live are most

active tissues.Material:

glycerol 3-phosphate (in intestine, monoacylglycerol also be used.) FFA (acyl CoA)

Processes: Monoacylglycerol pathway (intestine) Diacylglycerol pathway (liver, adipose)

The origins of glycerolIn intestine, liver and adipose tissues:

In liver and intestine:

dihydroxyacetone phosphate

glycerol

3-phosphateglucose

glycolysis dehydrogenate

glycerol glycerol 3-phosphate

phosphorylation

glycerokinase

Diacylglycerol pathway Diacylglycerol pathway

Acyl CoA transferase

CoA R1COCoA

CoA R2COCoA

Pi

CoA R3COCoA

PiPiCHCH22OO--

CHCH22OH OH

CHOH CHOH

3 - 磷酸甘油

PiPiCHCH22OO--

CHCH22OH OH

CHOH CHOH

3 - 磷酸甘油

O=

PiCHCH22OO--

CHCH22OO--CC--RR1 1

CHOCHO--CC--RR2 2

O=

磷脂酸

O=

PiCHCH22OO--

CHCH22OO--CC--RR1 1

CHOCHO--CC--RR2 2

O=

磷脂酸CHCH22OH OH

CHCH22OO--CC--RR1 1

CHOCHO--CC--RR2 2

O=

O=

1，2-甘油二酯

CHCH22OO--CC--RR3 3

CHCH22OO--CC--RR1 1

CHOCHO--CC--RR2 2

O=

O=

O=

甘油三酯

CHCH22OO--CC--RR3 3

CHCH22OO--CC--RR1 1

CHOCHO--CC--RR2 2

O=

O=

O=

甘油三酯

O=

PiCHCH22OO--

CHCH22OO--CC--RR1 1

CHOH CHOH

1-酯酰-3 - 磷酸甘油

O=

PiCHCH22OO--

CHCH22OO--CC--RR1 1

CHOH CHOH

1-酯酰-3 - 磷酸甘油

PiCHCH22OO--

CHCH22OO--CC--RR1 1

CHOH CHOH

PiCHCH22OO--

CHCH22OO--CC--RR1 1

CHOH CHOH

1-酯酰-3 - 磷酸甘油

Acyl CoA transferase

phosphatidase Acyl CoA transferase

glycerol 3-phosphate lysophosphatidate

phosphatidate Diacylglycerol triacylglycerol

Regulation of TAG metabolism

Acetyl CoA carboxylase (ACC)

activation: citrate,

dephosphorylation (insulin)

inhibition: palmitoyl CoA

long chain acyl CoA

phosphorylation (glucagon)

Carnitine acyltransferase Ⅰ inhibition: malonyl CoA

Section 8.3

Derivatives of Arachidonic Acid

Learned by yourself

Section 8.4

Metabolism of phospholipids

Phospholipids are phosphorous-containing lipids.

Including:

Glycerophospholipids (phosphoglycerides)

Sphingolipids

1.Metabolism of Glycerophospholipids

Consist of : glycerol, FA, phosphate group,

X group.

(cephalin)

(lecithin)

Diphosphatidylglycerol

cephalin

lecithin phosphatidyl serine

phosphatidyl inositol 1

1

(lecithin)

Hydrophilic head

Hydrophobic tail

Biosynthesis of glycerolphospholipids

Location:

endoplasmic reticulum and outermitochondrial membrane of all types of cells, mostly in liver, kidney, intestine.

Material:

FAs and glycerols (glucose, diet)

choline or serine, inositol (diet, synthesis)

ATP, CTP, Pi

Serine ethanolamine choline

3(S-adenosyl methionine)

CDP-ethanolamine CDP-choline

CHCH22OH OH

CHCH22OO--CC--RR1 1

CHOCHO--CC--RR2 2

O=

O=

1，2-甘油二酯DAG

CMP CMP

Phosphatidyl ethanolamine

Phosphatidyl choline

1.Diacylglycerol pathway

phosphoethanolamine phosphocholineCDP-choline

1

CDP-diacylglycerolPhosphatidyl glycerol inositol

1

1

1 1

cardiolipin

Phosphatidyl inositol

2. CDP-diacylglycerol pathway

Glycerol 3-phophate

Phosphotidic acid

2 acyl CoA 2CoA CTP ppi

serine

CMP

Phosphatidyl serine

Other methods

Phosphatidyl choline

3(S-adenosyl methionine)

Phosphatidyl ethanolamine

Phosphatidyl serine

change the head

Phosphatidyl ethanolamine

Degradation of glycerophospholipids

CH2O-C-R1

R2C-O-CH

CH2O-P-O—X

OH

OO

OO

OO

PLA1

PLA2

PLC

PLD

PLB2

PLB1

CH2OH

R2C-O-CH

CH2O-P-O—X

OH

OO

OO

CH2O-C-R1

HO-CH

CH2O-P-O—X

O

OH

O

Phopholipase

Metabolism of sphingolipids

sphingosine

sphingolipids

Hydrophilic head

Hydrophobic tail

Section 8.5

Metabolism of cholesterols

1

2

57

10

4

8

9

11

3

6

12

14

13

15

17

18

1916

21 22 24

25

26

27

20 23

Structure of cholesterolBase of the structure:

perhydrocyclopenano-phenanthrene

(four rings)

Total: 27 carbons

It is an alcohol found in animal

In plant(29C) In yeast(28C)

β-sitosterol ergosterol

1.Cholesterol Biosynthesis

Amount:

synthesis: 1g/day

diet: 0.3g/day

Location:

cytoplasm and endoplasmic reticulum of liver(80%), intestine(10%) and other tissues.

Material:

To one cholesterol:

18 acetyl CoA (glucose, amino acid)

36 ATP

16 NADPH+H+ (pentose-phosphate pathway)

Process:Three stages:

Conversion of acetyl CoA to mevalonate

(C6)

Conversion of mevalonate to squalene

(C30)

Squalene cyclization and conversion to cholesterol

(C27)

CoASH

CoASH

CHCH33CSCoA CSCoA

==OOCHCH33CSCoA CSCoA

==OO==OO CHCH33CSCoA CSCoA

==OOCHCH33CSCoA CSCoA

==OO==OO

CHCH33CCHCCH22CSCoA CSCoA ((乙酰乙酰乙酰乙酰CoACoA))

==OO ==OOCHCH33CCHCCH22CSCoA CSCoA

((乙酰乙酰乙酰乙酰CoACoA))

==OO==OO ==OO==OO

HOCCHHOCCH22CCHCCH22CSCoACSCoA((HMGCoAHMGCoA) ) CHCH33

OHOH

羟甲基戊二酸单酰羟甲基戊二酸单酰CoACoA==OO ==OO

HOCCHHOCCH22CCHCCH22CSCoACSCoA((HMGCoAHMGCoA) ) CHCH33

OHOH

羟甲基戊二酸单酰羟甲基戊二酸单酰CoACoA==OO==OO ==OO==OO

Acetoacetyl CoA

3-hydroxy-3-methylglutaryl CoA

Mevalonate (MVA)

HMGCoA reductase

(key enzyme)

1. Form MVA

2. Form squalene

cholesterol

squalene

MVA

5-pyrophospho-mevalonate

1

3.Form cholesterol

Regulation of cholesterol Biosynthesis

HMG CoA reductase:

1. phosphorylated (glucagon):

inactivation

dephosphorylated (insulin):

activation

2. feed back inhibition of cholesterol:

inhibit the formation of enzyme.

3. Feeding status: starvation: decrease the activation overeating: increase the activation

4. Feedback regulation of degradation : high sterol synthesis: high degradation low sterol synthesis: low degradation

Ch biotransformation and excretion

Conversion to Bile Acid (in liver)

1g ch is excreted as bile acid each day.

Conversion to cholesterol hormones (in adrenal cortex, testis, ovary)

pregnanes, androstanes, estranes, glucocorticoids, mineralocorticoids,

Conversion to 7-dehydrocholesterol (skin),

which can be change to Vit D3 by UV light.

Section 8.6

Metabolism of plasma lipoproteins

Plasma lipids

Including:

FFAs, TAGs, cholesterols (CH), cholesterol esters (CE), phospholipids (PL),

Total lipids: 5 mmol/LTotal TAGs: 0.11 ~ 1.69 mmol/L Total PL: 48.44 ~ 80.73 mmol/L Total CH: 2.59 ~ 6.47 mmol/L FFA : 0.195 ~ 0.805 mmol/L

Plasma lipoproteins

Lipoproteins are globular, micelle-like particles consisting of a hydrophobic core of triacylglycerols and cholesterol esters surrounded by an amphipathic coat of protein, phospholipid and cholesterol, acting as the transport form of plasma lipids.

protein

Classification:

Agarose gel electrophoresis:

♁ CM 1 前

Chylomicrons(CM)

Preβ lipoproteinsβ lipoproteins

α lipoproteins

Density gradient ultracentrifugation

Chylomicron, (CM)

Very low density lipoprotein, ( VLDL)

Low density lipoprotein, ( LDL)

High density lipoprotein, (HDL)

Apolipoproteins (apoproteins, apo):

Apolipoproteins are the proteins involved in the lipoproteins.

Classification:

Function:

-act as cofactors for lipid metabolism enzymes

-maintain the lipoprotein structure

apo A: AⅠ 、 AⅡ 、 A Ⅳapo B: B100 、 B48 apo C: CⅠ 、 CⅡ 、 C Ⅲapo D apo E

CM VLDL LDL HDL

electrophoresis CM Pre β β α

density ＜ 0.95 0.95~1.006 1.006~1.063 1.063~1.210

Composition:

TAG

80~90%

apo

1%

TAG

50~70%apo 5~10%

Ch and CE

40~50%

apo

20~25%

Lipids

50%

apo

50%

origin intestine liver VLDL/liver Intestine, liver

apolipoproteins apoB48, E A , ⅠA AⅡ Ⅳ 、 C ⅠCⅡ 、 CⅢ

apoB100 、 CⅠ 、C CⅡ Ⅲ 、 E

apoB100 apo AⅠ 、 AⅡ

Functions Dietary TAGs and cholesterol transport

Endogenous TAGs and cholesterol transport

Endogenous cholesterol and CE transport (from liver to tissue)

Reverse transport of

cholesterol and CE (from tissue to liver)

Abnormal metabolism of lipoproteinHyperlipoproteinemia (hyperlipidemia)

refer to abnormally high levels of lipids of lipoproteins in blood. It can be divided into 6 types.

Genetic disease:

associated with the mutation of key enzyme or apo involved in lipoprotein metabolism, such as: apoCⅡ 、 B 、 E 、 AⅠ 、 CⅢ ， LDL recepter.

Familial hypercholesterolemiainherited disorder of lipids.

Reason:

lack of functional LDL receptors

Characters:

elevated level of Ch in blood

cutaneous xanthoma in childhood

coronary artery disease （ atherosclerotic ， thrombus ）