KETOGENESIS AND

KETOLYSIS
SERGIO D. SANCHEZ VILLAMARÍN / BIOQUÍMICA
KETOGENESIS
AND KETOLYSIS:
“INDISPENSABLE
FOR BRAIN
NUTRITION”
ABSTRACT

The Ketone Bodies are important and

indispensable structures for providing energy
to the structures of the central nervous
system. These chemical structures are
generated thanks to the Liver and its
Mitochondria. This formation is thanks to the
metabolism of the fatty acids that provides
Acetyl CoA (source for the creation of
Acetone). If its drift comes from a process that
uses fatty acids, what the reader might think is
that it is a process that occurs in prolonged
fasting (when glucose and glucose in the form
of glycogen have run out), where it effectively
occurs in this way.
As soon as the individual has exhausted his or her
reserves of Glucose itself, two hormones (Epinephrine
and Glucagon) will activate a signaling pathway that will
activate the "Hormone Sensitive Lipase" in the
Adipocytes. The lipase, as it occurs in the endothelium
membrane and as it occurs in the adipocytes, has the
function of splitting the connection of the Triglyceride
packets. Triglycerides are structures that encapsulate
thanks to a Glycerol and three Fatty Acids (it does not
matter if they are the same or not).
PROCESS OF KETOGENESIS AND
KETOLISIS
KETOGENESIS
The transport of some Fatty Acids in the blood does not
necessarily require lipoproteins like HDL that carry
Cholesterol and Triglycerides (to a greater extent) to the
liver from the periphery. When they reach the liver, the
process of Beta-Oxidation is triggered, which I will
explain briefly:
The fatty acid is broken down into small fragments ( 18
or so) of Acil CoA. This process is done thanks to the
Acil CoA Synthase that uses ATP to "fix the process".
When Acil CoA is generated, a series of mechanisms are
produced that will be FAD, NAD and Water. When, at
some point in the process, we generate Beta CETO Acil
CoA the enzyme Thiolase for this compound generates
an Acetylcholine CoA and a Myriatic +CoA.
When we finally get Acetyl CoA this must be joined with
another similar molecule to form Acetyl CoA making us
lose a coenzyme A. Another thiolase acts in this
process. Thanks to the Hydroxymethylglutaryl-CoA
Synthase where it generates 3-Hydroxy-3-
methylglutaryl-CoA. After using a Liasa we pass from 3-
Hydroxy-3-methylglutaryl-CoA to Acetoacetate.
Acetoacetate can be converted into two things: 1. 3-
Hydroxybutyrate thanks to its dehydrogenase that uses
NAD and 2. A decarboxylation that does not use
enzymes produces Acetone that will go into the blood
and come out in the exaltation later.
KETOLISIS
To metabolize the ketone bodies (Acetoacetate and
Beta Hydroxy Butyrate) these must travel in the blood
from the Liver to the peripheral tissues and especially to
the brain. The fasting lipids cannot be absorbed by the
brain by itself since they cannot be absorbed by the
Hematoencephalic Membrane. The ketone bodies
generate either 23 ATP (Acetoacetate) or 26 ATP ( 3-
hydroxybutyrate or also called Beta-Hydroxybutyrate):
3-hydroxybutyrate is transformed into acetoacetate by
the use of NAD (a NADH generates 3 ATPs) thanks to its
dehydrogenase. Acetoacetate becomes Acetoacetyl-
CoA thanks to Thiophorase, an enzyme that uses
Coenzyme A from Krebs' Cycle Succinyl CoA. This
process uses a GTP. The Acetoacetyl CoA uses a
Thiolase (plus a CoA) to form 2 molecules of Acetyl CoA
where each one will provide me with 12 ATP. Therefore,
the final compendium of ATPs for 3-hydroxybutyrate is 26
ATPs (According to the most current literature Acetyl CoA
actually provides 10 ATPs and NADH 2.5 ATPs making the
final compendium more like 21.5 ATPs).
 MAP
This process is reminiscent of Gluconeogenesis and Glycolysis because of its curious way of using and
storing such a highly energetic substance so strictly.

Beta
Cetogénesis Cetolisis
Oxidación

a A
as o
Li GC
Ácidos Grasos Cetolisis y

M
H
Cetogénesis

Hipoglicemia Prolongada

Higado Adipocitos

Adipocito
Trigliceridos
LSH Beta Oxidación Glicerol Cetogénesis Cetolisis

NAD
3-HidroxibutiratoDesAsa
Acetoacetil NADH
Albumina Acido Graso
CoA

CoA HMGCoA Sintasa Aceto Acetato

Tiolasa
3-Hidroxi-3-metilglutaril CoA
Acil CoA Succinato
Transferasa
de CoA
Succinil
Aceto Acetato CoA
Acetil CoA Miristico + CoA
Acil CoA Beta
Insaturado Aceto Acetil
3HB DesH+Asa CoA
NADH NAD

Beta Hidroxi Beta-CETO

Acil CoA Acil CoA Tiolasa
Acetona 3-Hidroxi-Butirato

Acetil CoA Acetil CoA

CO2 Exalacion