Biochemistry from Dr. Dhiraj J. Trivedi SDM College of Medical Sciences and Hospital, Dharwad, INdia

1. Acetone bodies
OR
Ketone bodies

2. Introduction-
• Ketone bodies are namely-
• Acetoacetate
• Beta- hydroxy Butyrate and
• Acetone (a non metabolizable side
product)
• Synthesized from Primary substrates-
FFA

3. Their production-
• They are synthesized in liver
and are then transported to
peripheral tissues via blood.
• Normal level in blood is 1mg/dl.
(0.2 – 2.0 mmols / L)
• In urine concentration … which is
not easily detectable.

4. KetogenesisKetogenesis
Formation of ketone bodies
Site : Liver

5. β- Hydroxy β methyl
Glutaryl CoA
HMG CoA
Acetoacetyl CoA
Thiolase
Acetyl CoA
Acetyl CoA
CoA.SH
Acetyl CoA
CoA.SH
HMG CoA
Synthase
HMG CoA lyase
Aceto
acetate
Primary Ketone
bodies
Ketogenesis

6. β- Hydroxy butarate
dehydrogenase
NAD+
NADH + H+
Aceto acetate
β- Hydroxy Butyrate
Acetone
CO2
Spontaneous
Decarboxylation
Secondary
Ketone bodies
Ketogenesis

7. Acetyl CoA Acetyl CoA
Aceto acetyl CoA
Acetoacetate
Acetone
β Hydroxy butyric acid
Thiolase
CoA.SH
β- Hydroxy butyrate
dehydrogenase
NAD+
NADH + H+
CO2
CoA.SH
Minor pathway for ketogenesis in Liver

8. Excess production-
• In conditions like-
• Starvation
• Diabetes mellitus.
• Pregnancy
• Even high fat diet - called ketogenic diet

9. Excess production-
• During starvation and diabetes mellitus acetyl
CoA takes the alternative pathway i.e. instead
of TCA cycle it enters ketone body formation.
• In case of starvation, organs like brain get 60%
of their energy from ketone bodies.

10. Additional ketone bodies
• Amino acids like Leucine, Isoleucine,
Lysine, Tryptophan, Phenyl alanine and
Tyrosine are ketogenic.
• These amino acids produce Acetoacetyl
CoA or Acetyl CoA in liver and other
tissue.

11. •Ketolysis
•Degradation of ketone bodies

12. Tissues That Use Ketone Bodies
as fuel
• During Starvation:
• Brain
• Intestinal mucosa
• Adipocytes
• Developing fetus use ketone bodies
• All most all tissue Except Liver and
RBC

13. FFA
Acyl coA
acetoacetate
β -OH butyrate
2 Acetyl CoA
Acetoacetyl CoA
Acetoacetate
β -OH butyrate
succinate
Succinyl
CoA
Thiophorase
Thiolase
NADH + H
NAD
β -OH butyrate
DH
β oxidation

14. Energetics Ketone bodies
oxidation
• For Acetoacetyl CoA
• Equivalent to oxidation of two Acetyl
CoA in TCA ---- 20 ATP
• Utilized : One high energy phosphate
bond
• When Succinyl CoA is used …..Not
required.
• For β Hydroxy butyrate ..
• Additional 2.5 ATP from NADH

15. Liver can synthesize but ,
Can not metabolise Ketone
Bodies.
• The liver lacks
Thiophorase
• therefore is unable to use
acetoacetate as fuel.

16. Their importance-
• Importance source of energy for peripheral
tissues as-
a) soluble in aqueous solution.
b) produced in liver when amount of acetyl
coA present exceeds the oxidative capacity
of liver
c) used by extra hepatic tissue such as
skeletal ,cardiac muscle & renal cortex in
proportion to their conc.
In blood (also in brain during prolonged
starvation if their level rises sufficiently)

17. Regulation of Ketone body
metabolism

18. Regulation of Ketogenesis
• Three crucial steps
• 1. control of free fatty acid
mobilization from adipose tissue
• 2. Activity of carnitine acyl
transferase – I in liver
• 3. Partition of aceryl AoA between
two pathways Ketogenesis and TCA
cycle

19. ketosis
• ketonemia,
• ketonuria & smell of acetone in breadth.
• All above condition together leads to
ketosis• Diabetic ketoacidosis
• is a complication of diabetes mellitus
• caused by the buildup of by-products
of fat metabolism (ketones).
• Because glucose is not available as
a fuel source for the body cells.

20. Alcoholic keto-acidosis is
an accumulation of ketones (a type of acid)
in the blood,
caused by excessive alcohol consumption
Keto-acidosis - alcoholic
•Alternative names
•Definition

21. Contd…..
• The basic form of ketosis occurs in starvation
and involves depletion of available
carbohydrate coupled with mobilization of
FFA.
• This general pattern of metabolism is
exaggerated to produce the pathological
states found in Diabetes Mellitus, twin lamb
disease & ketosis in lactating cattle

23. In DM
Low insulin
Increased lipolysis & decreased
re-esterification of FFA
glucagon/ insulin ratio
Fatty acid oxidation
In liver Acetoacetate
Beta-OH-butyrate
(major fraction)
Acetone
(minor fraction)
NADH+H
NAD
CO2

24. Elevate blood glucose level–
by giving additional insulin,
As there is excessive fluid loss –
Replace fluids by IV fluid
Along with fluid there is Electrolyte loss
Replace fluid and Electrolytes
Treatment
I F E

25. What is ketogenic diet ?
• Ketogenic diet :
• 3: 1 ratio of lipid to carbohydrate
•In the treatment of pyruvate dehydrogenase deficiency,
ketone bodies can be used as fuel for brain in absence
of PDH and also provide source of Acetyl CoA.

26. Frequent urination or
frequent thirst for a day or more
Fatigue
Nausea and vomiting
Muscular stiffness or aching
Rapid deep breathing
Fruity breath (breath odor), Low blood pressure
Appetite – loss, Abdominal pain
A Patient suffering from following conditions:
What is your probable diagnosis ?

27. Fatigue , Slow, sluggish, lethargic movement
Breathing difficulty - leading to an abnormal breathing
pattern ,Irregular deep, Symptoms of dehydration, such as
dizziness
Confusion ,Agitation ,loss of consciousness
Lab test reports the following things:
•Blood and urine tests - Acidosis , Hypoglycemia,
•Blood chemistry tests – ketone bodies positive
•Tests quantify amount of alcohol in the blood
A patient reports with the following conditions:
What is the case ?

28. Causes of ketonemia
• Uncontolled Diabetes mellitus
• Starvation
• Chronic alcoholism
• Von- Gierke’s disease
• Heavy exercise
• Low carbohyderate diet for wt loss
• Glycogen storage disease Phosphorylase
kinase dificiency
• Pyruvate carboxylase deficiency

29. Causes of ketonemia
• Prolonged ether anesthesia
• Toxemia of pregnancy
• Certain conditions of alkalosis
• High fat feeding (ketogenic diet)

30. Starvation induced ketosis
• Prolonged fasting may be due to
• Inability to obtain food
• Desire to lose weight rapidly
• Trauma, surgery, neoplasms burns
• Decline insulin section
• Increased glucagon release