9_Fate of Acyl CoA in Fed and Fasted State (m2014)
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Transcript of 9_Fate of Acyl CoA in Fed and Fasted State (m2014)
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1Metabolic Changes Fed versus Fasted state
Fed State
Prevent hyperglycemia
Key pathways
Glycolysis
TCA
PPS
Glycogen synthesis
Fatty acid synthesis
Fasted State
Prevent hypoglycemia
Key pathways
oxidation
TCA
Glycogenolysis
Gluconeogenesis
STORAGE of EXTRA FUEL
Minimize Glucose Use
Provide Additional Glucose
Biochimie 87:81-86, 2005
??
After a meal, how to avoid Acyl CoA not get oxidized ?
Would Acyl CoA not feedback to inhibit ACC ?
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2Covalent regulation (phosphorylation) of
Acetyl CoA carboxylase by AMP-dependent
Kinase (AMPK), which itself is regulated both
covalently and allosterically.
Another short-term
regulation of activity
via reversible
phosphorylation
cAMP-dependent
mechanism
godsonx.blog.163.com/.../
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3http://www.namrata.co/category/metabolism-lipids/theory-notes-metabolism-lipids/
Requires glycerol backbone
Metabolic control to effect transfer of
carbon from liver to adipose tissue
Glyceraldehyde 3-phosphateDihydroxyacetone phosphate
Triose phosphate
isomerase
Glycolysis
Glycerol 3-phosphate
Glycerol-3-phosphate
dehydrogenase
Glycerol Glycolysis
Glycerol kinase*
(liver)
Glycerol 3-phosphate formation in liver and adipose tissue
Glucose
Glycerol kinase*
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4Acyl CoA
Acyl CoA
Acyl CoA
Triglyceride
VLDL
Glycerol-3-phosphate pathway
G 3-P
From ?
web.campbell.edu/.../308_lect/lect3/lect3.html
(+) or (-) signifies sites of positive or negative insulin effects;
HSL: Hormone sensitive lipase; TG: Triglycerides;
LPL: lipoprotein lipase; FFA: free fatty acids
Free fatty acids to and from adipose tissue
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5http://www.aps.uoguelph.ca/~swatland/HTML10234/LEC19/PS76.gif
by LPL
Via Glycerol 3-P pathway
Unloading blood triglyceride to adipocytes after a meal
Hormonal regulation of triacylglycerol
degradation in the adipocyte.
Lippincotts Illustrated Reviews: Biochemistry, 2011
Fatty acid metabolism in
fasting and fed states
In postabsorptive state and during fasting,
fatty acids are oxidized for energy
1. Mobilization [HSL]
2. Activation into fatty acyl CoA
by thiokinase in the cytosol
3. Transport into the mitochondria
by the carnitine shuttle
4. -oxidation
Fatty acids &
Glycerol
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6In postabsorptive state and during fasting, fatty acids are oxidized for energy
1. Mobilization
2. Activation into fatty acyl CoA by thiokinase in the cytosol
3. Transport into the mitochondria by the carnitine shuttle
4. -oxidation
Fatty acid metabolism in fasting and fed states
AMP
- oxidation
http://obm.sagepub.com/content/4/3/99/F1.large.jpg
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7Lippincotts Illustrated Review: Biochemistry, 2011
Acetone
Acetoacidic acid
-hydroxybutyric acid
Generally KB includes acetone, acetoacetate and -hydroxbutyrate (which in fact is a carboxylic acid)
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8Hydroxymethylglutaryl (HMG)
CoA synthase, mainly
found in the liver, catalyzes
the rate-limiting step
LeucineCholesterol
Lippincotts Illustrated Review: Biochemistry, 2011
Synthesis of ketone bodies
3-OH butyrate
Dehydrogenase
**
Lyase
3-OH butyrate
Dehydrogenase
* HMG CoA synthase
**Thiophorase = Succinyl CoA:acetoacetate CoA transferase
Lippincotts Illustrated Reviews: Biochemistry, 2011
Ketone body synthesis in the liver and use in peripheral tissues
*
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9Ketonemia & Ketonuria
-Could occur in cases of prolong starvation or sever diabetes mellitus
-Blood level of ketone bodies may exceed 90 mg/dL
(versus < 3 mg/dL in normal situation)
-Carboxyl group of a ketone body has a pKa ~4
- H+ in blood brings pH down acidosis (ketoacidosis)