Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol =...

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Triglyceride Metabolism Jack Blazyk 3/1/04

Transcript of Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol =...

Page 1: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Triglyceride

Metabolism

Jack Blazyk3/1/04

Page 2: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Triglyceride Metabolism

Triglyceride = Triacylglycerol = Depot Fat

CH2 — CH — CH2

l l lO O O

C=Ol l l

C=O C=Ol l lR R’ R’’

Ester

Glycerol backbone

FattyAcid

Page 3: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Triglyceride Metabolism

• Lipogenesis occurs mainly in liver, adipose and intestinal epithelial cells

• Lipolysis occurs in adipose cells

• Regulation via insulin and glucagon signals

Page 4: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

R-COOH

R-C-S-CoA

O

=

CoA-SH + ATP

AMP + PPi

Acyl-CoASynthase

Activation

Page 5: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

CH2 — C — CH2

l l lOH O O P

l

DHAP

Glycerol 3-PDehydrogenase

NADH + H+

NAD+

NADH + H+

NAD+

CH2 — CH — CH2

l lOH OH

lO P

Glycerol 3-P

Page 6: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

Glycerol

CH2 — CH — CH2

l lOH OH

lO P

Glycerol 3-P

CH2 — CH — CH2

l lOH OH

lOH

GlycerolKinase

ATP

ADP

Liverand kidney

Page 7: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

CH2 — CH — CH2

l lOH OH

lO P

Glycerol 3-P

AcylTransferases

2 Acyl-CoA

2 CoA

CH2 — CH — CH2

l lO O

C=Ol l

C=Ol lR R’

lO P

PhosphatidicAcid

Page 8: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

CH2 — CH — CH2

l lO O

C=Ol l

C=Ol lR R’

lO P

Phosphatidic Acid

Phosphohydrolase

PiH2O

CH2 — CH — CH2

l lO O

C=Ol l

C=Ol lR R’

lOH

1,2-Diacylglycerol

Page 9: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

CH2 — CH — CH2

l lO O

C=Ol l

C=Ol lR R’

lOH

Acyltransferase

CoAAcyl-CoA

1,2-Diacylglycerol Triacylglycerol

CH2 — CH — CH2

l l lO O O

C=Ol l l

C=O C=Ol l lR R’ R’’

Page 10: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipogenesis

• Intestinal epithelial cells

Export via chylomicrons

• Liver

Export via VLDL

• Adipose

Storage in cytoplasm

Page 11: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Marks’ Basic Medical Biochemistry: A Clinical Approach (Williams & Wilkins, 1996)

Page 12: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipolysis

Triacylglycerol

CH2 — CH — CH2

l l lO O O

C=Ol l l

C=O C=Ol l lR R’ R’’

Adipose Cells

Triglyceride Lipase(Hormone-Sensitive Lipase)

H20

CH2 — CH — CH2

l lO O

C=Ol l

C=Ol lR R’

lOH

1,2-Diacylglycerol

+ R’’-COOH

Free Fatty Acid

Page 13: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipolysis

CH2 — CH — CH2

l lO O

C=Ol l

C=Ol lR R’

lOH

1,2-Diacylglycerol

Diglyceride Lipase

H20

+ R-COOH

Free Fatty Acid

2-Monoacylglycerol

CH2 — CH — CH2

l lOH O

lC=OlR’

lOH

Adipose Cells

Page 14: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Lipolysis

Monoglyceride Lipase

H20

2-Monoacylglycerol

CH2 — CH — CH2

l lOH O

lC=OlR’

lOH

Adipose Cells

+ R’-COOH

Free Fatty Acid

CH2 — CH — CH2

l lOH OH

lOH

Glycerol

FFA are transported via albumin

Page 15: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Regulation of Lipolysis

ATP

ADP

Pi

H2OProtein Kinase ALipase Phosphatase

Triglyceride Lipase - OH

Triglyceride Lipase - P

ACTIVE

INACTIVE

Activated by insulin Activated by glucagon

Page 16: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

Regulation of Lipolysis

• Activators Glucagon Epinephrine ACTH TSH Growth hormone Glucocorticoids Thyroid hormones

• Inhibitors Insulin Free fatty acids

Page 17: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’
Page 18: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’
Page 19: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’
Page 20: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’
Page 21: Triglyceride Metabolism Jack Blazyk 3/1/04. Triglyceride Metabolism Triglyceride = Triacylglycerol = Depot Fat CH 2 — CH — CH 2 lll OOO C=O lll lll RR’R’’

To see this presentation on the web go to

Click on My TeachingThen click on Triglyceride Metabolism

http://www.oucom.ohiou.edu/dbms-blazyk