Lipid Metabolism synthesis and oxidation

metabolism

1. Advanced Nutritional Biochemistry
NF 765
Dr. Sana Janakat
Fall 2023
Lipid Metabolism
Synthesis and Oxidation

2. Energy source
70% of energy is stored as TG (most
efficient form)
It requires 1:1 (w:w) water (proteins and
glycogen require 1:4
Part of the structure of cell membrane
Lubricant (e.g. Meibomian glands in the eyelid)
Cell signaling (Extracellular and transcellular)
Biological roles for lipids

3. Occurs in
The liver:cholesterol (Ch) & TG (long chain F.A)
Adipose tissue: TG (long chain FA)
Mammary glands: Ch and TG medium c FA)
Sebaceous glands (TG {branched FA})
It is suppressed by high fat diet
It is extremely high in premature
infants despite fat content in the diet.
De novo lipogenesis

4. Synthesis Oxidation
Compartmentalization is vital to
separate the two processes (Fig 13-1)
Product of Synthesis is the precursor
of oxidation and vice versa
Elongation can occur + Acetyl CoA
Desaturation occurs by desaturases

5. Figure 13-1 Fatty acid synthesis

6. Uptake and storage of TG
Lipoprotein lipase synthesized in myocytes
and adipocytes* Luminal surface of
edothelial cells of blood capillary walls (Fig
13-7)
Lipoprotein Lipase
Lipoproteins Unesterified FA
Cross the endothelial cells
(Mechanism Unknown)
*Increase during fed state in adipocytes
*Increase during fasting state in myocytes

7. Figure 17-3: Model of the role of LPL in
transporting TG to adipocytes
Sulfated proteoglycan

8. Figure 13-8 Hydrolysis of stored TAG in adipose tissue by hormone sensitive lipase. R and C
represent the regulatory and catalytic subunits of cAMP -dependent protein kinase A

9. Hormone-sensitive lipase
TG Monoacylglycerol (sn-2)
Monoacylglycerol lipase
fatty acid + Glycerol
Inactivation
Dephosphorylation
Fed state Insulin
Tissues Liver
β-Oxidation
Gluconeogenesis
In adipocytes (Fig 13-8) Fasting state

10. 3 enzymes
Carnitine palmitoyltransferase-1 (CPT-1)
Integral protein in the outer mitochondrial
membrane
Fatty acyl-CoA + Carnitine FA carnitine + CoA
Carnitine-Palmitoylcarnitine translocase
Integral protein of inner mitochondrial membrane
Carnitine palmitoyltransferase-2 (CPT-2)
Peripheral protein on the inner mitochondrial memb
FA carnitine + CoA FA CoA + Carnitine
Role of Carnitine (Fig 13-9)

11. Figure 6.23 Membrane transport
system for fatty acyl CoA across
the inner mitochondrial membrane

12. Role of Carnitine
CH3 OH O
CH3-N-CH2-CH-CH2-COOH + R-C-SCoA
CH3
Carnitine activated fatty acid
Carnitine palmitoyl transferase
CH3 O-C-R
CH3-N-CH2-CH-CH2-COOH + H-SCoA
CH3
Acyl Carnitine Coenzyme A
O

13. Figure 13-9 Role of Carnitine in fatty acid transport into the mitochondria

14. Fed state Insulin Acetyl CoA
Carboxylase
Malonyl CoA
(Competitive inhibitor of CPT-1)
Entry of Fatty acids to mitochondria
β-Oxidation
Another role of Insulin

15. Fig 13-10:
β-oxidation
of fatty
acids.
Example is for
oxidation of
palmitoyl CoA.

16. Energy yield of B-oxidation of
palmitate
Palmitoyl CoA + 7 CoASH +7 FAD + 7 NAD
+
+7 H2O
8 acetyl CoA + 7 FADH2 + 7 NADH + H
+
8 x 12 = 96 7 x 2 = 14 7 x 3 = 21
131 -2*= 129 ATP
* Spent for the activation of the fatty acid

17. Same as the even number fatty acid,
but the last product is propionyl CoA
(Fig 13-13)
Propionyl CoA
Methyl malonyl CoA (MMA)
Succinyl CoA
Odd Number Fatty Acid Oxidation
Krebs
cycle
Methylmalonyl CoA mutase
Vitamin B12 depentdent

18. Figure 6.26 Oxidation of propionyl CoA

19. Figure 6.26 Oxidation of propionyl CoA

20. Fig 13-14:
Ketone body
formation

21. Fig 13-15:
Ketone body
metabolism