lipid metabolism in human body bioenergetics

bioenergetics

1. Lipid Metabolism

2. Sources of Fatty Acid Fuel
Diet Fat Storage Cells
Endogenous
production
Energy

3. Release of Fatty Acids from
Triacylglycerols
O
O
O
O O O
+
HOC-R
3 HOC-R
2
HOC-R
1
Triacylglycerol Glycerol
Lipases
CH
2OH
CHOH
CH
2OHCH
2OC-R
1
CHOC-R
2
CH
2OC-R
3

4. Acylglycerol Lipases
Triacylglycerol
Lipase
Diacylglycerol
Lipase
OH
OH
OH
Monoacylglycerol
Lipase
OH
OH
OH
Triacylglycerol (TAG)
Diacylglycerol (DAG)
Monoacylglycerol
(MAG)
Glycerol

5. 5
Phospholipase

6. Digestion of Dietary
Triacylglycerols
•Occurs in duodenum
•Facilitated by
•Bile salts (emulsification)
•Alkaline medium (pancreatic juice)
Pancreatic
lipases
OH
OH
TAG MAG
Intestinal
lipases Glycerol
+
Fatty Acids

7. Epithelial Cell (Intestinal Wall)
Intestinal lumen
MAG Glycerol Fatty Acids
TAG
Lipoprotein
ChylomicronsLymphatics
Blood Tissues

8. S
O
O
OH
N
H
HO OH
O
OH
H
H
H
taurocholic acid HO OH
O
OH
H
H
H
chenodeoxycholic acid

9. 9
Lipid Transporter (lipoprotein)
•Chylomicrons the lowest density lipoprotein
(95% lipids, primarily of triacylglycerols)
•VLDL very low-density lipoproteins (90-95%)
•LDL low-density lipoproteins (85%, cholesterol)
•HDL high-density lipoproteins (50%,
phospholipid & cholesterol)
•IDL intermediate-density lipoproteins (derived
from VLDLs in the formation of LDLs)

10. Adipose Cell
Hormone
(Adrenalin, Glucagon, ACTH)
Receptor
ATP c-AMP
Adenylyl
Cyclase
Activates
Activates lipase
Triacylglycerols Glycerol +
Fatty acids Blood
Lipolysis
Insulin
blocks this
step

12. ATP c-AMP AMP
Inactive Kinase Activated Kinase
Inactive Lipase Activated Lipase
P
Triacyl-
glycerol
Glycerol +
Fatty Acids
Phosphatase
(Hormone-sensitive
Lipase)
Insulin favors formation
of the inactive lipase
Adenylyl cyclase Phosphodiesterase
Enhanced by insulinEnhanced by glucagon

13. Beta Oxidation
•Cleavage of fatty acids to acetate in
tissues
•Occurs in mitochondria
9 CH
3
COSCoA
CO
2H
[O][O][O][O] [O][O][O] [O]

14. Steps in Beta Oxidation
•Fatty Acid Activation by Esterification
with CoASH
•Membrane Transport of Fatty Acyl CoA
Esters
•Carbon Backbone Reaction Sequence
•Dehydrogenation
•Hydration
•Dehydrogenation
•Carbon-Carbon Cleavage (Thiolase Reaction)

15. Net reaction:
FA + CoA + ATP  fatty-acyl-CoA + AMP + 2P
i
+ 34 kJ/mol
Fatty Acid Activation by Esterification with CoASH

16. •FA with  12 carbons enter mitochondrial matrix (MM)
•FA with  14 carbons use CARNITINE SHUTTLE
OH
-
O
O
N
+
carnitine
Rate-limiting step of FA oxidation
Membrane Transport of Fatty Acyl CoA Esters

17. Source: http://cellbio.utmb.edu/cellbio/mitochondria_1.htm
Carnitine acyltransferase I Carnitine acyltransferase II
Translocase

18. Beta Oxidation Reaction Sequence
Occurs in Mitochondria
Repeat Sequence

19. Complete Beta Oxidation
of Palmitoyl CoA
CH
3CH
2--CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2COSCoA
7 Cycles
8 CH
3COSCoA + 7 FADH
2 + 7 NADH + 7 H
+

20. Energetics of Complete
Oxidation of Fatty Acids
Palmitic Acid Palmitoyl CoA -2
CH
3
COSCoA CO
2
+ H
2
O 108
High Energy Phosphate
Bonds Generated
Net 106
TCA Cycle
106 High Energy Phosphate Bonds G
0’
= 3,233 KJ/Mole
For Palmitic Acid CO
2:
G
0’
= - 9,790 KJ/Mole
Efficiency
of -Oxidation = 33%

21. 21
•1 cycle of -ox:
–Palmitoyl-CoA (16 carbons):
–Overall oxidation of palmitate:
Palmitoyl-CoA + CoA + FAD + NAD
+
+ H
2O Myristoyl-CoA + acetyl-CoA + FADH
2 + NADH + H
+
Palmitoyl-CoA + 7CoA + 7FAD + 7NAD
+
+ 7H
2O 8 acetyl-CoA + 7FADH
2 + 7NADH + 7H
+

22. 22
Calculated yield of ATP
Oxidation Step NADH /
FADH
2
ATP
Palmitic Acid to Palmitoyl CoA - 2
Palmitoyl CoA to Acetyl-CoA7 NADH
7FADH
2
21
14
Acetyl-CoA to CO
2
+ H
2
0 (TCA
Cycle)
24 NADH
8 FADH
2
8 ATP
72
16
8
Total 129

23. 23
Regulation

24. Beta Oxidation of Odd
Carbon Fatty Acids
CH
3CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2CH
2--CH
2COSCoA
5 Cycles
5 CH
3COSCoA + CH
3CH
2COSCoA
Propionyl CoA
CO
2H
COSCoA
H-C-CH
3
CO
2H
COSCoA
CH
3-C-H
HO
2CCH
2CH
2COSCoA
D-Methylmalonyl
CoA
L-Methylmalonyl
CoA
Succinyl CoA
TCA Cycle
Propionyl CoA
Carboxylase
ATP/CO
2
Epimerase
Mutase
Vit. B
12

25. Beta Oxidation of
Unsaturated Fatty Acids
HH
CH
3(CH
2)
7-C=C-CH
2(CH
2)
6COSCoA
HH
CH
3(CH
2)
7-C=C-CH
2COSCoA
H
H
CH
3(CH
2)
7-CH
2-C=C-COSCoA
Oleoyl CoA
Beta Oxidation
(3 Cycles)
cis-
3
Isomerase
trans-
2
Continuation of Beta Oxidation

26. Beta Oxidation of Branched
Chain Fatty Acids
CH
3 CH
3
CH
3(CHCH
2CH
2CH
2)
3CHCH
2CO
2H
Phytanic Acid
(from breakdown of chlorophyll)
CH
3 CH
3
OH
CH
3(CHCH
2CH
2CH
2)
3CHCHCO
2H
CH
3 CH
3
CH
3(CHCH
2CH
2CH
2)
3CHCO
2H
-Hydroxylase
-Oxidation
(in peroxisomes)
CO
2
Pristanic Acid

27. Beta Oxidation of Branched
Chain Fatty Acids (Cont’d)
CH
3 CH
3
CH
3(CHCH
2CH
2CH
2)
3CHCO
2H
Pristanic Acid
CH
3 CH
3
CH
3(CHCH
2CH
2CH
2)
3CHCOSCoA
Pristanoyl CoA
Beta Oxidation
(6 cycles)
CH
3CHCOSCoA + 3 CH
3CH
2COSCoA + 3 CH
3COSCoA
CH
3
iso-Butyryl CoA Propionyl CoA Acetyl CoA
HO
2CCH
2CH
2COSCoA
Succinyl CoA
TCA Cycle