Lipid Metabolism III

1
Lipid Metabolism III

• Dr. Khanittha Taneyhill
• Division of Clinical Chemistry
• Department of Medical Technology
• Faculty of Associated Medical Sciences
• Chiang Mai University

2
Lipoprotein Metabolism
60-70 enter to liver via apo B/E receptors
TG
TG
B
B
B
LPL
LPL
C
C
LDL
Liver
B
IDL
VLDL
D
D
E
E
Nascent VLDL
Apoprotein
Apoprotein
D
C
E
D
C
E
Phospholipase
Cholesterol esterase
LCAT
Liver Intestine
A1
C
C
A
Nascent HDL
HDL
3
Lipid metabolism
Lipid ????????????? ???????????????????????
Triglyceride ??????????????????????????????????
Metabolism ??????????? ????????????????????? Lip
id ???????????????????? membrane glycerophospholi
pids sphingomyelins glycolipids cholesterol Li
pid ??????????????????????????????????????????????
?????????????? ???? eicosanoids
4
????????????? Triglyceride
Monoacylglycerol pathway
Fatty acid CoA ATP acyl CoA
AMP Ppi Acyl CoA 2-monoacylglycerol
diacylglycerol CoA Diacylglycerol acyl
CoA triglyceride CoA
Glycerol phosphate pathway
Glycerol-3-P acyl CoA
lysophosphatidic acid CoA Lysophosphatidic
acid diacylglycerol Pi Diacylglycerol
acyl CoA triglyceride CoA
5
??????? Triglyceride
Fed state
Glucose
TG
Glucose

Chylomicron
Insulin
DHAP

TG
Remnant
Glycerol-3-P
LPL
VLDL

CII
FACoA
IDL
FA
FA
LDL
glycerol
Adipose cell
Blood
6
??????? Triglyceride
Fasted state
TG
Lipase (inactive)
cAMP
PKA

Low insulin/high glucagon

ATP
Hormone sensitive Lipase-P (active)
FA
FA
FA
FA
FA
FA
Glycerol
Glycerol
Blood
Adipose cell
7
Fatty acid
Fatty acid-albumin complex (blood)
Fatty acid (cytosol)
ATP, CoA
AMP, PPi
Acyl CoA (cytosol)
Cytosol
CoA-SH
CAT-I
Mitochondrial Inner membrane
Carnitine
Acyl-carnitine
CAT-II
Mitochondrial matrix
CoA-SH
Acyl-CoA
Beta-oxidation
8
??????????????????????????
Activation ??????? FA ???? acyl CoA
?????????????? acyl CoA synthase
3
4
1
????? acyl CoA ???? mitochondria Acyl CoA ????
membrane ?????? ????????? carnithine shuttle
?????????????? 2 ???????????????? ??? carnithine
acyltransferase I ??? II (CAT-I, CAT-II)
2
5
9
Beta-Oxidation
Dehydrogenation ??? acyl CoA dehydrogenase ??
FAD ?????????? H ???????????????????? tran
??????? C2 ??? C3 ?????? FADH2
1
Hydration ?????????????? ????????? L-hydroxyacyl
CoA ?? OH ??? C3
2
Dehydrogenation ??? NAD ?????????? H ?????????
ketoacyl CoA ??????????????? C3 ???????? ??????
NADH
3
Thiolytic cleavage ??????????? ketoacyl CoA ???
acetyl CoA ??? acyl CoA ?????????????????? C
?????????????? 2 ?????
4
10
Metabolism ???????????
Ketone bodies ????????
Ketone bodies ??? acetoacetate, b-hydroxybutyrate
??? acetone ?????????????? mitochondria
???????????
Ketone bodies ????????????????????????
??????????????????????????? ???? ???? fasting,
starvation, high-fat diet ??? ???????
????? insulin ???? glucagon ?????????
??????????????????? ?????????? lipogenesis
?? acetyl CoA ????????????????????????????????????
??????????
11
Ketogenesis
HMG-CoA
12
Ketolysis
????????????? Ketone bodies ??????????????????????
???????????? ???????????? enzyme b-ketoacid CoA
transferase ???????????? acetoacetate ???????
acetoacetyl CoA ????????????????????????????????
??? ???? ????????????????????????
?????????????????? ?????????????????????????
??????????????????????????????????????????
13
???? Ketosis

• ?????????? ???????????????????????? ketone bodies
  ???? ??????????? ??????????????????????????
  ????????????? 1 mg/dl ????????????????? 20 mg/day
  ????????????????
• ?????? Ketosis ???? 3 ???
• Ketonemia ??????? ketone bodies ??????????
• Ketonuria ???????? ketone bodies ?????????????
• Ketone breath ???????????????????

14
???? Ketosis

• ????????? Ketone bodies ??????????????????
  ?????????????????????????? ketone bodies ???????
• ???????????????????????????????????
  ???????????????? bicarbonate ???????????
• hemoglobin ????????????????????
  ???????????????????????????? (Dyspnea)
  ???????????????
• ??????????????????????????????????????
  ?????????????????????? ??????????????????????
  (dehydration) ????????

15
???????????????? ketone bodies ?????????

• ???????????????? ?????????????????????????????
  ???????????? ??????
• ??????? ???????????? insulin
• ?????????? (Starvation) ??????????????? glycogen
  ????????????????? ?????????????????????????????
• ??????????????? (Overeating) ?????????????????????
  ???? carbohydrate ???????????????? acetyl CoA
  ?????????????????????????
• ?????? ketone bodies ????????????????????????????
  
• 78 ???? b-hydroxybutyric acid, 20 ????
  acetoacetate ??? 2 ???? acetone

16
(No Transcript)
17
Ketone bodies analysis
1. Gerhardt test Urine FeCl3 --gt dark
purple detect AcAc 25-50 mg/dl
salicylate phenol antipyrine interfere 2.
Nitroprusside test of Rothera AcAc Acetone
Nitroprusside ----gt purple complex modified
Labstix, Tablet, Ring test

NH4OH
18
Ketone bodies analysis
3. Beta-OH butyrate b-OH butyrate
NAD Acetoacetate NADH H


(340 nm)
b-OH butyrate dehydrogenase
pH 8.5
Diaphorase
NADH INT NAD Formazan
(oxidized)
(reduced, 505 nm)

INT p-Iodonitrotetrazolium violet
24-Iodophenyl-34-nitrophenyl-5- phenyltetrazo
lium chloride
19
????????????? Lipid metabolism

• Fatty liver (????????????) ???? TG ??????????????
  ???????
• 1.1 ??????????????????????? ????????????????????
  ???????
• 1.2 ??????????? ??????????????? lipoprotein
  ????????? ??????? lipotropic factor ???? choline
  ??????????? ????????? phospholipid
• 1.3 ???? cell injury ?????? ???????????? ??????
  ????????????? ???????????
• Obesity (???????????) ?? TG ??????????????????????
  ?????? ???????????????????????????????????????????
  ???????????????

1
2
20
(No Transcript)
21
TG synthesis
22
(No Transcript)
23
Cholesterol synthesis
(C6)
(C5)
(C30)