Subcellular Locations of Lipid Metabolism

Glyoxysomes
Glyoxysomes

Malic enzyme: Malate

NADP+

Pyruvate + CO2
NADPH + H+

Fatty Acid Biosynthesis

Different enzymes from those in fatty acid -oxidation
Activation of acetyl-CoA required
Spiral metabolic pathway
Formation of Malonyl-CoA by acetyl-CoA carboxylase
- An irreversible and committed step for fatty acid biosynthesis in
animals
- Biotin as a prosthetic group in the enzyme

Formation of Palmitic Acid (16:0) by Fatty Acid Synthase

- A multifunctional enzyme complex (7 enzymatic activities)
Overall reaction:
8 Acetyl-CoA + 7 ATP + 14 NADPH + 14 H+
Palmitic acid + 7 ADP + 7 Pi + 6 H2O + 8 CoA-SH (Co-enzyme A)
Summary of 2 parts
Formation of 7 malonyl-CoA:
7 acetyl-CoA + 7 CO2 + 7ATP 7 malonyl-CoA + 7ADP + 7Pi

7 cycles of condensation and reduction:

Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH + 14 H+
Palmitic acid + 7 CO2 + 8 CoA-SH + 14 NADP+ + 6 H2O

Acyl carrier protein (ACP)

- A protein co-enzyme for attachment of substrates and intermediates

during fatty acid biosynthesis
- Part of the fatty acid synthase complex

H SACP (Abbreviated form)

Fatty acid biosynthesis

by fatty acid synthase
(FAS) complex:

Initiation reactions of fatty acid biosynthesis

HS-Cys (FAS),

Fatty acid catabolism vs anabolism

oxidation

reduction

hydration

dehydration

oxidation

reduction

thiolysis

condensation

Tricarboxylate transport system

Inner membrane
- Impermeable to
acetyl CoA

What are the sources

of acetyl-CoA for fatty
acid biosynthesis?
Fatty acid
biosynthesis

Amino
acids

Pyruvate
dehydrogenase

Glucose

Elongation and desaturation of fatty acids

Formation of Acyl-CoA is required
before elongation or saturation:

[Animals and human do not

have enzymes to introduce
double bonds beyond C-9]

*Essential
fatty acids

(ARA)

Linolenate + CoA-SH
AMP + PPi

ATP

[Both the acyl chain and NADH are oxidized by O2]

(condensation)

thioesterase

ARA + CoA-SH

Biosynthesis of Triacylglycerols (in cytosol)

Fatty acids are stored in adipose tissues as triacylglycerols
~15 kg triacyglcerol in a 70-kg man
Excess carbohydrate is converted to triacylglycerols
Formation of glycerol
backbone:

(DHAP)
NADH
Glycerol-3-phosphate
dehydrogenase

(in liver
and kidney)

Phospholipid
biosynthesis

(a diacylglycerol-P)

(fatty acid)

Phosphatic acid
phosphatase

Pi

acyl
transferase

acyl
transferase

Acylation
of free
hydroxyl
groups

acyl
transferase

Triacylglycerol

Sites of regulation of fatty acid metabolism

Triacglycerols
- Fuel for energy-requiring
processes
- Storage for future use
- Synthesis and breakdown
involve different tissues (liver
and adipocytes)
Action of hormones
- Glucagon increases cAMP levels
- Insulin decreases cAMP levels

Malonyl-CoA
- Inhibits entry of fatty acyl-CoA
into mitochondria
Long term regulation
- Changes in enzyme quantities