FA Metabolism Flashcards
Nomenclature for double bonds
Number corresponds to number of carbons away from carbonyl carbon, inclusive
Most common saturated FA
Palmitic acid
Most common unsaturated FA
Oleic acid
Overview
Glycerol-3P is created from DHAP, then combined with free FA’s to create triglycerides
Where is Triglyceride stored?
In adipose tissue, for use of other tissues
In muscle, for its own use
What is the result of an overflow of excess lipids
Lipids begin to be stored in other tissues, such as the liver and muscle leading to insulin resistance
What breaks down TG to DAG?
Adipose Triglyceride Lipase
What breaks down DAG to MAG?
Hormone Sensitive Lipase
What breaks down MAG to glycerol and free FA?
MAG Lipase
Which hormones stimulate lipolysis?
Epinephrine, Glucagon
3 macro steps of FA breakdown
1) Acylation of FA’s via acyl-CoA
2) Transport into mitochondria via Carnitine shuttle
3) ß-oxidation
What is special about acyl-CoA synthase in terms of energy?
It uses ATP which gets converted into AMP and PPi because the bond is so high-energy, which allows the reaction to be pulled to the right
Describe the Carnitine shuttle
CPT-1 combines Acyl-CoA with Carnitine to produce fatty acyl-carnitine, which is then transported across the IMM by Translocase
CPT-II splits fatty acyl-carnitne into Acyl-CoA and Carnitine which is cycled back out
CPT = Carnitine Palmitoyl Transferase
First step of beta-oxidation
Acyl-CoA to trans-∆2-enoyl-CoA via Acyl CoA DH
FAD -> FADH2
Feeds into ETC
Second step of beta-oxidation
trans-∆2-enoyl-CoA to L-3-hydroxyacyl-CoA
via Enoyl-CoA hydratase
Input of H2O
Third step of beta-oxidation
L-3-hydroxyacyl-CoA to 3-Ketoacyl-CoA
via L-3-hydroxyacyl-CoA DH
NAD to NADH
Feeds into ETC
Fourth step of beta-oxdation
3-Ketoacyl-CoA to Acyl-CoA + Acetyl-CoA
via ß-ketothiolase
Input of CoA
Inhibition of Carnitine shuttle via Malonyl-CoA
ACC (acetyl-CoA carboxylase) creates Malonyl-CoA (inhibitory)
Inhibition of ACC via AMPK/PKA signals a low-energy state and stopping of FA synthesis
Prevention of Malonyl-CoA synthesis, resulting in de-inhibiton of Carnitine shuttle
AMPK
AMP-activated protein kinase
Describe MCAD
Medium-chain Acyl-CoA DH deficiency (first step in ß-oxidation)
Hypoglycemia
- no FA oxidation, so glucose used up
- no FA, so no gluconeogenesis
Ketone body pathway synthesis first step
2 Acetyl-CoA via Thiolase to Acetoacetyl-CoA
Ketone body pathway synthesis second step
Addition of another Acetyl-CoA to produce HMG-CoA via HMG-CoA synthase
Ketone body pathway synthesis third step
Loss of acetyl-CoA produces acetoacetate
Ketone body pathway synthesis fourth step
Acetoacetate can produce acetone and D-3-Hydrozybutyrate (all ketone bodies) via DH
