They are water soluble substances.
2. They are synthesized at a relatively low rate in well nourished individuals.
3. Plasma level of ketone bodies < 1mg/dl.
4. Urinary level of ketone bodies <3 mg/24 hour urine.
Formation and utilization of ketone bodies; ketoacidosisJinal Tandel
Formation and utilization of ketone bodies is part of lipid metabolism. After completion of this topic one can understand about Ketogenesis, utilization of Ketone bodies and ketoacidosis
They are water soluble substances.
2. They are synthesized at a relatively low rate in well nourished individuals.
3. Plasma level of ketone bodies < 1mg/dl.
4. Urinary level of ketone bodies <3 mg/24 hour urine.
Formation and utilization of ketone bodies; ketoacidosisJinal Tandel
Formation and utilization of ketone bodies is part of lipid metabolism. After completion of this topic one can understand about Ketogenesis, utilization of Ketone bodies and ketoacidosis
Ketone Bodies
Fatty acids undergo 𝛽-oxidation in the liver mitochondria to generate a high amount of energy and form three compounds, that are known as “ketone bodies”. These ketone bodies are water-soluble and do not require lipoproteins for transportation across the membrane. Ketone bodies are lipid molecules having a carbonyl group attached to two -R groups.
The three ketone bodies formed are –
1. Acetoacetate
2. D-3-hydroxybutyrate
3. Acetone
Ketogenesis – Definition
Ketogenesis is a catabolic pathway of metabolism. In this process, fatty acids and certain ketogenic amino acids are broken down to derive energy by alternative means. Ketone bodies are produced in the ketogenesis process.
Our body continuously produces ketone bodies in low amounts, but in certain cases like starving, when carbohydrates are present in less amount in diet, ketogenesis is preferred to compensate for the energy requirements.
Ketone bodies accumulated in an excess amount may lead to a condition called ketoacidosis, which may be fatal.
Ketogenesis Pathway
Our body normally derives energy from stored carbohydrate by the process of glycogenolysis (glycogen → glucose) or from non-carbohydrate sources such as lactate by the process of gluconeogenesis.
Ketogenesis occurs continuously in a healthy individual, but under certain conditions, when there is an increased concentration of fatty acids or carbohydrate reserves are decreased, ketogenesis happens at a higher rate:
• Under low blood glucose level, e.g. during fasting or starvation
• On exhaustion of carbohydrate reserve, e.g. glycogen
• When there is insufficient insulin, e.g. Type-1 diabetes
All the main body parts such as the brain, skeletal muscles, heart, etc. can utilise the energy formed by ketogenesis.
Insufficient gluconeogenesis results in hypoglycemia and excessive production of ketone bodies resulting in a fatal condition called ketoacidosis.
Ketogenesis Steps
The ketogenesis process occurs primarily in the mitochondria of liver cells. Below are the steps in the process of ketogenesis:
1. Transfer of fatty acids in mitochondria by carnitine palmitoyltransferase CPT-1
2. 𝛽-oxidation of fatty acid to form acetyl CoA
3. Acetoacetyl-CoA formation: 2 acetyl CoA form acetoacetyl CoA. The reaction is catalyzed by the enzyme thiolase
4. 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthesis: the step is catalyzed by HMG-CoA synthase
5. Acetoacetate formation: HMG-CoA is broken down to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase
Acetoacetate thus produced forms other ketone bodies, acetone by decarboxylation and D-3-hydroxybutyrate by reduction.
Significance of Ketogenesis
• Ketogenesis is used to get energy by the brain, heart and skeletal muscles under fasting condition
• The ketogenic diet (low-carb, fat-rich diet) is used these days to lose weight.
KETONE BODY METABOLISM. FOR MBBS, BDS, LABORATORY MEDICINE pptxRajendra Dev Bhatt
Ketone bodies are produced from acetyl-CoA, mainly in the mitochondrial matrix of liver cells when carbohydrates are so scarce that energy must be obtained from breaking down of fatty acids.
The importance of Ketone bodies have been depicted in this presentation. Ketone bodies are very significant and produce ATPs for our body during extreme conditions.
Our Brain completely relies on the Ketone bodies for energy during fasting. Liver is the organ that metabolises these Ketone bodies.
Definition of Ketone bodies, types, uses etc... are clearly presented.
Hello friends ,this presentation is all about ketone bodies .this will help you to understand what are ketone bodies and their functioning .it will benefit specially bpharmacy students.
Ketone bodies, or simply ketones are substances produced by the liver during gluconeogenesis, a process which creates glucose in times of fasting and starvation. There are three ketone bodies produced by the liver. They are acetoacetate, beta-hydroxybutyrate, and acetone. These compounds are used in healthy individuals to provide energy to the cells of the body when glucose is low or absent in the diet.
Lipid metabolism is the synthesis and degradation of lipids in cells.
It involves the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes.
In animals, these fats are obtained from food or synthesized by the liver.
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ketogenesis and utilisation of ketone bodies.pptx
1. KETONE
BODIES
• INTRODUCTION
• Ketone bodies are metabolic products
that are produced in excess during
excessive breakdown of fatty acids.
• Acetoacetate, acetone and β-
hydroxybutyrate are collectively
known as ketone bodies (acetone
bodies).
• Only the first two are true ketones
while β-hydroxybutyrate does not
possess a keto (C=O) group.
• Ketone bodies are water-soluble and
energy yielding.
• In a normal man, concentration of
ketone bodies in the blood is usually
less than 3 mg/100ml.
2. SIGNIFICANCE OF KETONE
BODIES
Alternate source to glucose for energy needs
• Ketone bodies represent an alternative to glucose for the provision of
energy to the cells.
Production of ketone bodies under
conditions of cellular energy deprivation
• Ketone bodies are produced when excessive fatty acids are being
oxidized (because of increased adipose tissue lipolysis) and glucose
availability to the cells is limited.
• Such situations are seen in conditions such as diabetes mellitus and
starvation.
Utilization of ketone bodies by the brain
• Brain normally utilizes glucose for energy needs.
• Although ketone bodies cannot completely replace glucose for energy
needs in the brain, brain gets adapted to oxidize ketone bodies during
prolonged fasting and starvation.
3. KETOGENESIS
DEFINITION
• The process of the formation of ketone bodies is collectively called as
ketogenesis.
TISSUES
• Ketone bodies are synthesized only in liver.
LOCALIZATION OF REACTIONS
• The synthetic reactions occur in mitochondria since enzymes are
localized in the mitochondria.
REACTIONS
•
•
• The major pathway of ketone body formation is HMG CoA lyase
pathway.
• The reactions of this pathway are:
1. Formation of acetoacetyl CoA
Two molecules of acetyl CoA condence to form acetoacetyl CoA.
This reaction is catalyzed by thiolase, an enzyme involved in the final
step of β- oxidation.
4. 2. Formation of β-hydroxymethyl
glutaryl CoA
• Acetoacetyl CoA combines with another molecule of acetyl CoA to
produce β-hydroxy β-methyl glutaryl CoA (HMG CoA).
• HMG CoA synthase, catalysing this reaction, regulates the
synthesis of ketone bodies.
3. Formation of acetoacetate
• HMG CoA lyase cleaves HMG CoA to produce acetoacetate and
acetyl CoA.
4. Formation of β-hydroxybutyrate
• Acetoacetate can undergo spontaneous decarboxylation to form
acetone.
5. Formation of acetone
• Acetoacetate can be reduced by a dehydrogenase to β-
hydroxybutyrate.
CONDITIONS FOR KETONE BODIES
OVERPRODUCTION
• In certain conditions, such as during prolonged starvation or impaired
glucose oxidation (diabetes mellitus), fat becomes the source of
energy and its degradation is greatly accelerated.
6. REGULAITION OF
KETOGENESIS
• Ketogenesis is regulated mainly by:
1. Substrate availability
• Increased ketogenesis occurs when there is excessive availability of fatty
acids for oxidation. Thus, increased ketogenesis occurs during starvation or
diabetes mellitus.
2. Regulation of β-oxidation
• Increased glucagon and decrease insulin in fasting result in inhibition of
acetyl CoA carboxylase.
• This results in decrease in malonyl CoA.
• Decreased malonyl CoA results in increased β-oxidation of fatty acids
(activtion of carnitine palmitoyl transferase I).
3. Availability of ATP
• Increased β-oxidation results in more production of ATP through citric acid
cycle in liver.
• This results in increased availability of acetyl CoA for ketogenesis.
4. Induction of HMG CoA synthase
• HMG CoA synthase is the rate limiting enzyme in ketogenesis.
• The synthesis of HMG CoA synthase is stimulated by fasting, increased intake of
fat and diabetes mellitus.
• Fatty acids are strong inducers of HMG CoA synthse.
• The increased synthesis of enzyme occurs by increased transcription.
7. 3. Availability of ATP
• Increased β-oxidation results in more production of ATP
through citric acid cycle in liver.
• This results in increased availability of acetyl CoA for
ketogenesis.
4. Induction of HMG CoA synthase
• HMG CoA synthase is the rate limiting enzyme in ketogenesis.
• The synthesis of HMG CoA synthase is stimulated by
fasting, increased intake of fat and diabetes mellitus.
• Fatty acids are strong inducers of HMG CoA synthse.
• The increased synthesis of enzyme occurs by increased
transcription.
8. UTILIZATION OF KETONE
BODIES(KETOLYSIS)
INTRODUCTION
• Ketone bodies are utilized for energy needs in the extrahepatic tissues
such as brain, heart, skeletal muscle and kidney.
• The two ketone bodies-acetoacetate and β-hydroxybutyrate serve as
important sources of energy for the peripheral tissues.
• The tissues which lack mitochondria (e.g. erythrocytes) however, cannot
utilize ketone bodies.
• During prolonged starvation, ketone bodies are the major fuel source for
the brain and other parts of CNS.
• The ketone bodies can meet 50-70% of the brain’s energy needs.
REACTIONS
• The major pathway of ketone bodies utilization is Transacylase pathway.
1. Formation of acetoacetate from β-hydroxybutyrate
• β-hydroxybutyrate is converted to acetoacetate by β-hydroxybutyrate
dehydrogenase.
9. 2. Formation of
acetoacetyl
CoA
• Acetoacetate is activated
to form acetoacetyl CoA
by the transfer of CoA
molecule from succinyl
CoA.
• The reaction is catalyzed
by succinyl
CoA:Acetoacetate CoA
transferase.
3. Formation of acetyl
CoA
• Acetoacetyl CoA is cleaved
to form acetyl CoA and
acetyl CoA in a reaction
catalyzed by thiolase.
11. KETOSIS
DEFINITION
• Ketosis is a disorder of excessive production of ketone bodies.
CAUSE
• Excessive ketone bodies are produced mainly in two conditions:
1. Starvation (carbohydrate deprivation)
2. Uncontrolled diabetes mellitus (impaired uptake of glucose by the
peripheral
tissues).
BIOCHEMICAL AND CLINICAL FINDINGS
• The important features of ketosis are ketonemia, ketonuria, acetone
odor of breath, metabolic acidosis and hyperkalemia.
1. Ketonemia
• In ketosis, the plasma concentration of ketone bodies is well above
normal limits. The condition is called ketonemia.
2. Ketonuria
• When the concentration of ketone bodies significantly increased
(above
70mg/dl) in plasma, they appear in urine. The condition is called
ketonuria.
12. 3. Acetone in
breath
• Acetone is also excreted by the lungs and produces a characteristic odor in
breath
(acetone odor of breath).
4. Metabolic acidosis
• Metabolic acidosis is caused by excessive accumulation of β-
hydroxybutyrate and acetoacetate.
5. Hyperkalemia
• Acidosis results in the shift of potassium from intracellular to
extracellular compartment.
BIOCHEMICAL DIAGNOSIS
1. β-hydroxybutyrate in plasma
2. Acetoacetate in urine
3. Rothera’s test
MANAGEMENT
1. Provision of glucose to the tissues
• Ketosis is suppressed by restoring adequate level of carbohydrate
metabolism.
2. Correction of electrolyte imbalance and acid-base imbalance
• Metabolic acidosis is corrected by bicarbonate administration.
13. TESTS FOR DETECTION OF KETONES IN URINE
1. ROTHERA’S’ TEST (Classic Nitroprusside Reaction)
Acetoacetic acid or acetone reacts with nitroprusside in an alkaline
solution to form a purple-colored complex . Rothera’s test is sensitive to
1-5 mg/dl of acetoacetate and 10-25 mg/dl of acetone.