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Lecture

Biochemistry 2280A Lecture Notes - Ketone Bodies, Ketone, Adipocyte


Department
Biochemistry
Course Code
BIOCHEM 2280A
Professor
Eric Ball

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16 – Acetyl-CoA part 2: Fatty acids, ketone bodies, and
biosynthesis
Release of acetyl-CoA from fatty acids storage
Low glucose conditions
Breaks down triaglycerols in
adipocyte; lipase will break the
fatty acids off glycerol
Fatty acids go to liver and muscle, NOT brain
Converted to acetyl-CoA via β-oxidation
Glycerol foes to liver
Fuel for gluconeogenesis
Activation of fatty acids in cytosol
Fatty acyl-CoA Is transported into the mitochondrial matrix; driven by the hydrolysis of ATP
β -oxidation of fatty acids in matrix
Fatty acid goes through a series of 4 cheimcal reactions each set of reactions get an acetyl-CoA, and
NADH, and FADH2 and an acyl-CoA that is 2 carbons shorter.
Net reaction for acyl-CoA with:2N” carbons:
Acyl-CoA + N-1 FAD + N-1 NAD+ + N-1 CoA N Acetyl Co-A (enters CAC or in liver made ketone bodies) + (N-1
FADH2 + N-1 NADH) ETC
FADH2 comes from different sources
Each FADH2 gives electrons to Q to make QH2, but using different protein
complexes
β -oxidation of fatty acids: special cases
Oxidation of unsaturated fatty acids yields fewer FADH2 and may consume
NADPH
Oxidation of “odd chain” fatty acids yields one propinyl-CoA, which enter the CAC as succinyl-CoA
Ketone Bodies
How acetyl-CoA is transported from liver to other tissues
Brain usually likes glucose but in starvation will switch over to
ketone bodies
Breaking down tricylglycerides during fasting, most acetyl-CoA
made in the liver will be made into ketone bodies to be sent to the brain
Once in the brain transferred back to acetyl-CoA and goes into CAC
Muscle will also pick up ketone bodies – selfish
Fatty Acid Biosynthesis High glucose conditions – storing energy as fats
Requires NADP+
Acetyl-CoA made in the matrix and fatty acids are synthesized in cytosol -
need to transport
Tricarboxylate Transport System
Moves acetyl-CoA from matrix to cytosol
Series of reactions that consumes 2ATP, and 1 NADH and produce one NADPH
Synthesis of fatty acids in cytosol
Similar to β-oxidation of fatty acids but in reverse
Consumes NADPH instead of NADH or FADH2
1ATP consumed per “cycle”
Palmitate (C16:0) most commonly formed, need 8 turns around cycle from one palmitate
However can make all kinds of fatty acids
Net reaction for Palmitate (C16:0):
8 Acetyl-CoA + 14 NADPH + 7 ATP Palmitate + 8 CoA + 14 NADP+ + 7 ADP + 7
Pi
Enzymes exist to add double bonds
Fatty acids are stored as triacylglycerols or used to make membrane lipids
Regulation - glucogon (low sugar need to mobilize energy stores) and insulin (high
blood glucose, favour storage – synthesis of fatty acids from acetyl-CoA) effect the
regulation
Synthesis and Breakdown Pathways
Glycolysis and the citric acid cycle provide precursors for synthesis of many
biomolecules
Cholesterol synthesis
All carbons of cholesterol are derived form acetyl-CoA
Protein as an energy source
Amino acids can be converted to intermediates in glycolysis and the citric acid
cycle
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