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 ?

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/.../

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*

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

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

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

7Lippincotts Illustrated Review: Biochemistry, 2011

Acetone

Acetoacidic acid

-hydroxybutyric acid

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

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

*

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)