[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Ketogenesis
It is the formation of ketone bodies in the liver
mitochondria.
Ketone bodies are:
Acetoacetate, -hydroXybutarate and acetone.

Under normal fed state, the hepatic production of acetoacetate

and -hydroXybutarate is minimal and the concentration of these
compounds in the blood is very low (does not eXceed
1 mg %)

Synthesis of ketone bodies

In ketogenesis
Large amounts of acetyl CoA accumulate.
Two acetyl CoA molecules combine to form acetoacetyl
CoA by thiolase enzyme.
Acetoacetyl CoA hydrolyzes to acetoacetate, a ketone
body.
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[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Acetoacetate reduces to -hydroxybutyrate .

Or loses CO2 to form acetone, both ketone bodies.

-Hydroxybutyrate Dehydrogenase
CH3
C

H
+
O NADH NAD HO
+

CH3
CH

CH2

CH2

COO

COO

acetoacetate

D--hydroxybutyrate

Both acetoacetate and -hydroXybutarate can be transported

across the mitochondria membrane and the plasma membrane of
the liver cells.
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[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

After which they enter the blood stream to be used as a fuel by

other cells of the body.
In the blood stream, small amounts of acetoacetate are
decarboXylated to acetone.
It is volatile and can not be detected in the blood.
The odor of acetone may be detected in the breath and also
detected in the urine of person who has high level of ketone
bodies in the blood.
Ketolysis
Utilization of acetoacetate and -hydroXybutyrate by eXtra
hepatic tissues. E.g. cardiac , skeletal muscles, kidney and
brain. In starvation.
This pathway describes the conversion of ketone bodies,
acetoacetate and beta-hydroxybutyrate, to acetyl-CoA
which feeds into the TCA cycle.
Utilization of ketone bodies requires that acetoacetate is
reactivated forming acetoacetyl coA.
This is done by a mitochondrial enzyme acetoacetate
succinyl coA transferase uses succinyl coA then
acetoacetyl coA is cleaved into 2 acetyl coA molecules by
thiolase.
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[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Which can then enter citric acid cycle with production of

energy.

Ketosis:
It is the accumulation of ketone bodies in the blood (ketonemia)
and their appearance in the urine (ketonuria) together with
acetone odor in the breath and acetone can be detected in urine.
The simplest cause of ketosis is prolonged starvation with
deficiency in the carbohydrates for energy production.

Cholesterol
Cholesterol can be derived from the diet or manufactured de
novo in all the cells of humans especially in the liver, intestine,
adrenal corteX and reproductive organs.

[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Cholesterol concentration in plsama of healthy people is

150-200 mg/dl.
Function of cholesterol:
It is the precursor of steroid hormones (seX hormones)
It is the precursor of bile acids and bile salts.
It is precursor of vitamin D3.
Synthesis of cholesterol occurs in the cytoplasm where the
enzymes are present.
Synthesis of cholesterol
Cholesterol is synthesized from cytosolic acetyl CoA
It starts by the condensation of three molecules of acetyl CoA
with the formation of

3-hydroXy-3 methyl glutaryl CoA

(HMG CoA).

[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

HMG-CoA Reductase catalyzes production of mevalonate

from HMG-CoA. Using 2 NADPH.

Mevalonate is converted to isopentenyl pyrophosphate.

[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

6 molecules of isopentenylpyrophosphate are converted to

squalene (30) carbons. With then cyclization and demethylation
give cholesterol.
Regulation of cholesterol synthesis
HMG-CoA Reductase, the rate-determining step on the
pathway for synthesis of cholesterol.

Plasma lipoproteins
All lipids in plasma are transported in the form of lipoproteins.
Plasma lipoproteins have the central core formed of non polar
lipids ( triglycerols and esterified cholesterol) the outer layer
contains the more polar lipids ( phospholipids)and non esterified
cholesterol) and proteins (apoproteins).
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[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Classification of Lipoproteins
There are four main classes of lipoproteins:

Chylomicrons
Triglycerides form 90% of total lipids in them, protein is
about 1%.
Apo-A and apo-B48.

Very Low Density Lipoproteins (VLDL).

They are synthesised in the liver.
It contains apoprotein B-100

Low Density Lipoproteins (LDL) (Bad cholesterol)

All LDL arise from VLDL
They are rich in cholesterol
Apo B100.

High Density Lipoproteins (HDL) (Good cholesterol)

They contain large amount of proteins (40%) and very
little triglycerides.
They are formed from phospholipid bilayer, free
cholesterol and apo C.
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[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Function of lipoproteins
Lipoprotein
Chylomicrons

Function
transport lipids absorbed from a meal
from the intestines to the adipose tissue
and, to a lesser degree, to the liver, for
storage

very low-density

transport lipids, from the liver to (newly

lipoproteins

synthesised triglycerides) from the liver to

(VLDL)

adipose tissue

low-density

transport lipids, particularly cholesterol,

lipoproteins (LDL) and neutral fats (triglycerides), from the

liver to most tissue cells for their various
metabolic purposes
high-density

transport lipids, particularly cholesterol,

lipoproteins (HDL) and neutral fats (triglycerides), to the liver

for catabolism and elimination

[LIPIDS METABOLISM- KETOGENESIS]

December 8, 2013

Quiz on lipid metabolism- ketogenesis

Enumerate ?
1- Types of ketone bodies

2- Types of lipoprotein and their function

3- Steps of ketogenesis

4- Formation of cholesterol

5- Composition of low density lipoprotein

.
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