BIOC 311 Lecture Notes - Acetyl-Coa, Succinyl-Coa, Acetoacetic Acid

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Published on 19 Nov 2012
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BIOC 311, Lecture 24, 31-10-2012
Ketogenesis
- excess a-CoA is converted into acetoacetone, acetone and β-hydroxybutyrate “ketone bodies”
- ketone bodies are water soluble
Ketolysis
- Process by which ketone bodies are converted into E that fuels extrahepatic tissues
- glycolysis, Fa ox and some aa ox makes a-CoA, which are turned into ketones
- a-CoA will accumulate in liver and become HMG-CoA, which will then lose a acetyl-CoA
and be coverted into 3 ketone bodies
- only liver and kidney can accumulate ketone bodies
- acetone is useless
- TCA is also somewhere where a-CoA can go
- Generation of ketone bodies happens normally at low levels, a-CoA normally shunted into it
and its source is glucose
Production of ketone bodies is in response to low blood glucose
- glucose levels in specific tissue remain constant (brain, RBC) while the rest of the body
increase in [ketones] due to lipolysis
- FA major source of ketone bodies due to its ox
2
Ketone Bodies in a Nutshell...
3 acetyl CoAs
HMG-CoA
acetoacetate
acetyl CoA
acetoneβ-hydrox ybutyrate
Glycolysis
FA Ox idation
Some Amino Acids
ex haled
from lungs
acetoacetateβ-hydrox ybutyrate
2 acetyl CoAs
Peripheral
FA Synthesis or
TCA Cycle
excreted
by k idneys
Liver Tissue
Peripheral Tissues
E.A. DENNIS 2010
©
Blood
Peripheral Tissues
Peripheral Tissues
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Ketogenic a-CoA from β-oxidation of fatty acid
- when blood glucose is low, oaa in liver is used for gluconeogenesis
- ooa in liver is used to make glucose in the liver, meaning that FA derived A-CoA in the liver
cannot be used in the TCA cycle
Synthesis of a-CoA
- same pathway as cholesterol biosynthesis
biosynth shuts down in starvation
location is diffent (mito vs cyto)
- made during starvation
initially feeds other organs so the brain can get all the glucose
after a few weeks, the brain uses ketone bodies too
- step 1: thiolase takes two acetoCoA and makes acetoacetyl-CoA
- step 2: aa-CoA another a-CoA and water is taken by HMG-CoA synthetase to make 3-
hydroxy-3-methylglutaryl CoA
- step 3: HMG-CoA lyase forms acetoacetate and a-CoA from HMG
β-hydroxybutyrate and acetone
- made from D-3-hydroxybutyrate which undergoes dehydrogenation with NAD+ (reversible)
Which direction is goes is dependent on amount of NAD+ and NADH
- makes acetoacetate, which is unstable and spontaneously decarboxylates into acetone
Peripheral use of ketone bodies
Beta Oxidation In a Nutshell...
One iteration of β-Oxidation:
Make fatty acyl CoA.
Step 1: Oxidize the β-carbon (C3)
Step 2: Hydrate the β-carbon
Step 3: Oxidize the β-carbon, again!
Step 4: Thiolyze α−β bond, releasing acetyl CoA
REPEAT from step 1, w/ 2 fewer carbons
Fatty Acid
Acyl CoA
(1)
Enoyl CoA
(2)
L-hydroxyacyl CoA
(3)
Ketoacyl CoA
(4)
Acyl CoA
(shorter)
Acetyl CoA
TCA Cycle
E.A. DENNIS 2010
©
Beta Oxidation In a Nutshell……
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