RUMINANT KETOSIS

(ACETONEMIA)

Submitted by:
Rajesh Khant
L-2016-V-07-M
Dept. Of Animal Nutrition
NOTE-
Normally, total body needs of energy (ATP) is met by various fuels .

1. Carbohydrates (glucose) - 70%.

2. Fat (fatty acids) - 25%.

3. Proteins (Amino acids) - 5%.

4. Ketone bodies normally - negligible %.

 INTRODUCTION
High glucose demand & intense adipose mobilization causes ketosis.
Both these condition are present in early lactation, at this time negative energy
balance leads to adipose mobilization & milk synthesis creates high glucose
demand.

Adipose mobilization is accompanied by high blood serum concentration of non-

esterified fatty acids(NEFA).

During period of intense gluconeogenesis, a large portion of serum NEFA is

directed to ketone body synthesis in the liver.

Ketone bodies are acetone, acetoacetate & -hydroxy butyrate (BHB).

Thus, clinico-pathologic characterization of ketosis include high serum
concentration of NEFA & ketone bodies & low concentrations of glucose.
 CAUSES OF KETOSIS
Uncontrolled diabetes mellitus
Starvation
Chronic alcoholism
Von- Gierkes disease
Heavy exercise
Low carbohydrate diet- For weight loss
Glycogen storage disease type 6(Due to phosphorylase kinase deficiency)
Pyruvate carboxylase deficiency
 KETOGENESIS
Ketogenesis takes place in liver using Acetyl-CoA as a substrate or a precursor
molecule.

Enzymes responsible for ketone body formation are associated mainly with the
mitochondria

Steps :

Two molecules of acetyl-CoA condense to form acetoacetyl-CoA. This reaction

is catalyzed by thiolase enzyme.
1. ACETONE
- Acetone-breath has been used as a crude method of diagnosing individuals with untreated
Type I diabetes mellitus.

2. D (-)-3-Hydroxybutyrate (-Hydroxy Butyrate)

- It is the predominant ketone body present in the blood and urine in ketosis.
- The -hydroxybutyrate dehydrogenase reaction has two functions:
1) it stores energy equivalent to an NADH in the ketone body for export to the tissues, and
2) it produces a more stable molecule.

NOTE- The ratio of hydroxybutyrate to acetoacetate depends on the NADH/NAD+ ratio inside
mitochondria. If NADH concentration is high, the liver releases a higher proportion of -
hydroxybutyrate
 Liver v/s Peripheral tissues for ketones as fuel molecules
The enzyme, Succniyl-CoA Acetoacetate-CoA transferase, also known as Thiophorase,
is present at high levels in most tissues except the liver.

Very low level of enzyme expression in the liver allows the liver to produce ketone bodies but
not to utilize them.

This ensures that extra hepatic tissues have access to ketone bodies as a fuel source
during prolonged fasting and starvation.
 Regulation of Ketosis- Overview

During high rates of fatty acid oxidation, primarily in the liver, large amounts of
acetyl-Co A are generated. These exceed the capacity of the TCA cycle, and one
result is the synthesis of ketone bodies.
 FACTORS AGGREVATING KETOSIS
DECREASED CONCENTRATION OF OAA
1) (AS GLUCONEOGENESIS---INCREASED )

DECREASED ACETYL CoA UTILISATION

DECREASED TCA

INCREASED CONCENTRATION OF ACETYL Co A

2) INCREASED FREE FATTY ACIDS

DECREASED ACETYL Co A
CARBOXYLASE

DECREASED MALONYL Co A

INCREASED CARNITINE PALMITOYL

TRANSFERASE

INCREASED ACYL CO A OXIDATION

INCREASED ACETYL COA
3)
INSULIN / GLUCAGON RATIO DECREASED

INCREASED LIPOLYSIS IN ADIPOSE TISSUE

INCREASED ACETYL Co A

KETONE BODIES
STARVATION INDUCED KETOSIS

In early stages of starvation

, heart and skeletal muscle
consume primarily ketone
bodies to preserve glucose
for use by the brain.

After several weeks of

starvation, ketone bodies
become the major fuel of
the brain.
DIABETIC KETO- ACIDOSIS

Diabetic Ketoacidosis may

be diagnosed when the
combination
of hyperglycemia (high
blood sugars), ketones on
urinalysis and acidosis
are demonstrated.
1. Blood Sugar Level

In normal animal (cow) In ketosis

40mg/dl blood Reduced

2.Ketones Bodies in Blood

Ketone bodies Normal value In ketosis

Acetoacetic acid 0.1mg/dl Increase up to 7mg/dl

BHB 8 mg/dl Increase up to 30mg/dl
Free fatty acids 9 mg/dl Increase up to 28 mg/dl

(Veterinary Mercks Manual)

THANK YOU..