Metabolic Changes Fed versus Fasted state

Fed State

Fasted State

Prevent hyperglycemia
Key pathways
Glycolysis
TCA
PPS
Glycogen synthesis
Fatty acid synthesis

Prevent hypoglycemia
Key pathways
oxidation
TCA
Glycogenolysis
Gluconeogenesis
Minimize Glucose Use

STORAGE of EXTRA FUEL

Provide Additional Glucose

After a meal, how to avoid Acyl CoA not get oxidized ?

Would Acyl CoA not feedback to inhibit ACC ?

Biochimie 87:81-86, 2005

Another short-term
regulation of activity
via reversible
phosphorylation

cAMP-dependent
mechanism

Covalent regulation (phosphorylation) of

Acetyl CoA carboxylase by AMP-dependent
Kinase (AMPK), which itself is regulated both
covalently and allosterically.

godsonx.blog.163.com/.../

Metabolic control to effect transfer of

carbon from liver to adipose tissue

Requires glycerol backbone

http://www.namrata.co/category/metabolism-lipids/theory-notes-metabolism-lipids/

Glucose
Glycerol kinase*

Triose phosphate
isomerase
Glycerol-3-phosphate
dehydrogenase
Glycerol 3-phosphate

Dihydroxyacetone phosphate

Glyceraldehyde 3-phosphate

Glycerol kinase*
(liver)

Glycerol

Glycolysis

Glycolysis

Glycerol 3-phosphate formation in liver and adipose tissue

Glycerol-3-phosphate pathway
VLDL
G 3-P

Acyl CoA

From ?

Acyl CoA
Acyl CoA

Triglyceride

Free fatty acids to and from adipose tissue

(+) or (-) signifies sites of positive or negative insulin effects;

HSL: Hormone sensitive lipase; TG: Triglycerides;
LPL: lipoprotein lipase; FFA: free fatty acids
web.campbell.edu/.../308_lect/lect3/lect3.html

Unloading blood triglyceride to adipocytes after a meal

Via Glycerol 3-P pathway

by LPL

http://www.aps.uoguelph.ca/~swatland/HTML10234/LEC19/PS76.gif

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

Hormonal regulation of triacylglycerol

degradation in the adipocyte.
Fatty acids &
Glycerol

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
2. Activation into fatty acyl CoA by thiokinase in the cytosol
3. Transport into the mitochondria by the carnitine shuttle
4. -oxidation

AMP

- oxidation

http://obm.sagepub.com/content/4/3/99/F1.large.jpg

Lippincotts Illustrated Review: Biochemistry, 2011

Acetone
Acetoacidic acid
-hydroxybutyric acid

Generally KB includes acetone, acetoacetate and -hydroxbutyrate (which in fact is a carboxylic acid)

Hydroxymethylglutaryl (HMG)
CoA synthase, mainly
found in the liver, catalyzes
the rate-limiting step
Leucine

Cholesterol

Synthesis of ketone bodies

Lippincotts Illustrated Review: Biochemistry, 2011

**

*
Lyase
3-OH butyrate
Dehydrogenase

3-OH butyrate
Dehydrogenase

Ketone body synthesis in the liver and use in peripheral tissues

* HMG CoA synthase
**Thiophorase = Succinyl CoA:acetoacetate CoA transferase
Lippincotts Illustrated Reviews: Biochemistry, 2011

Ketonemia & 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)