BIOENERGETICS: Fatty Acid Catabolism, Oxidation, and Synthesis

This assignment comprehensively explores fatty acid catabolism, encompassing various metabolic pathways and processes. It begins by illustrating the entry of glycerol into the glycolytic pathway and the activation of fatty acids before their transport into mitochondria. The document then delves into the β-oxidation of saturated and unsaturated fatty acids, detailing the reactions and overall processes involved. Furthermore, it examines how acetyl-CoA, produced during fatty acid oxidation, enters the citric acid cycle. The assignment also contrasts fatty acid synthesis and breakdown, highlighting the roles of glycolysis and beta-oxidation, along with the involvement of carnitine acyl transferase. Additionally, it covers ω-oxidation of fatty acids, including the structural conversions and the flow chart of this process. Finally, the assignment elucidates the formation of ketone bodies, including the reactions, structures, and the overall flow chart of their synthesis, providing a complete understanding of fatty acid metabolism and its related pathways.

BIOENERGETICS
FATTY ACID CATABOLISM

ENTRY OF GLYCEROL TO GLYCOLYTIC PATHWAY:
Glycerol + ATP → L-Glycerol 3-phosphate + ADP
L-Glycerol 3-phosphate + NAD+→ Dihydroxyacetone phosphate + NADH + H+
Dihydroxyacetone phosphate →D-Glyceraldehyde 3-phosphate
D-Glyceraldehyde 3-phosphate → Glycolysis
Figure 1entery of glycerol to glycolytic pathway
FATTY ACIDS ARE ACTIVATED AND TRANSPORTED INTO MITOCHONDRIA:
Fatty acid + CoA + ATP → Fatty acyl-CoA +AMP + 2Pi ΔG ° = -34 KJ/mol′

Β OXIDATION OF SATURATED FATTY ACIDS:
Palmitoyl CoA + FAD → trans Enoyl CoA + FADH2
trans Enoyl CoA + H2O → β-Hydroxy acyl CoA
β-Hydroxy acyl CoA + NAD+ → β-ketoacyl CoA + NADH + H+
β-ketoacyl coA CoA-SH → Acyl-CoA + Acetyl CoA
overall reaction:
Palmitoyl CoA + 7CoA + 7FAD + 7NAD+ + 7H2O → 8 Acetyl CoA + 7FADH2 + 7NADH + 7H+
Figure 2 : β oxidation

ACETYL-COA CAN BE FURTHER OXIDIZED IN CITRIC ACID CYCLE:
Palmitoyl-CoA + 7CoA + 7O2 + 28Pi + 28ADP 8Acetyl- CoA + 7H2O + 28ATP
8 Acetyl- CoA + 16CO2 + 80Pi + 80ADP 8CoA + 80 ATP + 16CO2 + 16H2O
Sum of the above reactions is;
Palmitoyl-CoA + 23O2 + 108Pi + 108ADP CoA + 108 ATP + 16CO2 + 23H2O

OXIDATION OF UNSATURATED FATTY ACIDS:
Oleoyl-CoA cis-Dodecenoyl-CoA
cis-Dodecenoyl-CoA trans-Dodecenoyl-CoA
trans-Dodecenoyl-CoA 6 Acetyl-CoA
FATTY ACIDS SYNTHESIS AND BREAKDOWN:
Fatty acid synthesis (liver & adipose):
Dietary carbohydrates Glucose Acetyl-CoA Malonyl-CoA
Enoyl-CoA isomerase
5 Cycles of
Beta oxidation
3 Acetyl-CoA
3Cycles of
Beta oxidation
Glycoly
sis
Beta
oxidation
Fatty acids
multist
ep

Fatty acid beta oxidation (Mitochondria):
Fatty acids Fatty acyl-CoA Fatty acyl carnitine
In inner membrane:
Fatty acyl carnitine Fatty acyl-CoA Acetyl CoA
ω-OXIDATION FATTY ACIDS:
Fatty acid + 1/2O2 → fatty omega hydroxyacid
Fatty omega hydroxyacid + NAD+ → Fatty omega aldoacid + NADH + H+
Fatty omega aldoacid + NAD+ → Fatty dicarboxylic acid + NADH + H+
STRUCTURE OF ω-OXIDATION FATTY ACIDS:
Carnitine acyl
transferase
CoASH Carnitine

Figure1. Conversion of Lauric Acid (C12) to Fatty Alcohol
Figure2. Conversion of Fatty Alcohol to Fatty Aldehyde
Figure3. Conversion of Fatty Aldehyde to Fatty Carboxylic Acid
FLOW CHART OF ω-OXIDATION FATTY ACID:

Figure4. Omega Oxidation of Fatty Acid in the ER (Liver and Kidney)
FORMATION OF KETONE BODIES:
2 Acetyl CoA ⇌ Acetoacetyl CoA + CoA-SH
Acetoacetyl CoA + Accetyl CoA + H2O ⇌ β-Hydroxy- β-methylglutaryl-CoA + CoA-SH
β-Hydroxy- β-methylglutaryl-CoA ⇌ Acetoacetate + acetyl CoA
Acetoacetate + NADH + H+ ⇌ Acetone + α-β-Hydroxybutyrate + NAD+ + CO2
(All this reaction occur in liver then passes into blood to body tissues where again converted into
Acetyl CoA)
α-β-Hydroxybutyrate as a fuel
α-β-Hydroxybutyrate + NAD+ ⇌ Acetoacetate + NADH + H+

Acetoacetate + Succinyl CoA ⇌ Acetoacetyl CoA + Succinate
Acetoacetyl CoA + CoA-SH ⇌ 2 Acetyl CoA
FORMATION OF KETONE BODIES:
Figure5. Conversion of Acetyl CoA from Fatty Acid Oxidation to Ketone
bodies
STRUCTURES OF KETONE BODIES:
Figure6. Conversion of 2 Acetyl-CoA to Acetoacetyl-CoA
Figure7. Conversion of Acetoacetyl to Acetoacetate

Figure8. Conversion of Acetoacetate from D-B-Hydroxybutyrate to Acetone
FLOW CHART OF KETONE BODIES
Figure9.Ketone Bodies Synthesis