This document discusses ketone bodies and ketosis. It defines ketone bodies as water-soluble transporters of acetyl units produced in the liver from fatty acids during periods of low carbohydrate availability. The three main ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone. Ketone bodies serve as an alternative fuel for tissues like the brain during glucose deprivation. The document outlines the pathways of ketone body synthesis in the liver and utilization in other tissues, as well as conditions that cause excess ketone production (ketosis).
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.
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.
De novo synthesis of fatty acids (Biosynthesis of fatty acids)Ashok Katta
Synthesis of fatty acids in the body. Detailed pathway for de novo synthesis of fatty acids in the body including its energetic and regulation. also cover Multienzyme complex
De novo synthesis of fatty acids (Biosynthesis of fatty acids)Ashok Katta
Synthesis of fatty acids in the body. Detailed pathway for de novo synthesis of fatty acids in the body including its energetic and regulation. also cover Multienzyme complex
Gluconeogenesis- Steps, Regulation and clinical significanceNamrata Chhabra
Gluconeogenesis- Thermodynamic barriers, substrates of gluconeogenesis, reciprocal regulation of glycolysis and gluconeogenesis, biological and clinical significance
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.
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.
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
Cholesterol is the major sterol in the animal tissues.
Cholesterol is present in tissues and in plasma either as free cholesterol or as a storage form, combined with a long-chain fatty acid as cholesteryl ester. This presentation provide an overview of how cholesterol and ketone bodies are synthesised.
The citric acid cycle is the central metabolic hub of the cell.
It is the final common pathway for the oxidation of fuel molecule such as amino acids, fatty acids, and carbohydrates.
Copper- sources, daily requirement, absorption, transportation, storage, excretion, role in enzymatic action, role in iron metabolism, role in elastin maturation, role in bone formation, copper deficiency, copper toxicity, Wilson disease, Menkes disease.
Folic acid- Chemistry, One carbon metabolism and megaloblastic anemiaNamrata Chhabra
Folic acid- Structure, forms, absorption, transportation, storage, excretion, role in one-carbon metabolism, role in methionine synthesis, role in nucleotide biosynthesis, folate trap, folate antagonists, megaloblastic anemia
Sugar derivatives and reactions of monosaccharidesNamrata Chhabra
Reactions of monosaccharides, osazone formation, reduction, oxidation, reaction with acids and alkalies, ester formation and formation of amino sugars, amino sugar acids and deoxy sugars.
Definition of ELISA, Immunochemical principle of ELISA, Direct, Indirect, Sandwich and Competitive ELISA, applications of ELISA in the diagnostic field, and benefits/drawbacks of ELISA.
Molecular biology revision-Part 3 (Regulation of genes expression and Recombi...Namrata Chhabra
Regulation of gene expression in prokaryotes and eukaryotes, Recombinant DNA technology, Southern hybridization, Northern Hybridization, Western hybridization, cloning, PCR, Applications of RDT, Animal cloning, Multiple choice questions
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
2. Learning objectives
By the end of this presentation you will be
able to understand :
• Types of ketone bodies
• Significance of ketone bodies
• Steps of synthesis and utilization of
ketone bodies
• Conditions causes ketosis
2/20/2017 Namrata Chhabra, M.D. 2
3. What are ketone bodies ?
• Ketone bodies can be
regarded as water-soluble,
transportable form of acetyl
units.
• Acetoacetate, D(-3) –
hydroxy butyrate (Beta
hydroxy butyrate), and
acetone are often referred to
as ketone bodies.
2/20/2017 Namrata Chhabra, M.D. 3
4. Ketone bodies
• The term "ketones" is a misnomer
because 3-hydroxybutyrate is not a
ketone and there are ketones in
blood that are not ketone bodies,
e.g., pyruvate, fructose.
• Fatty acids released by adipose tissue
are converted into acetyl units by the
liver, which are then exported as
ketone bodies.
2/20/2017 Namrata Chhabra, M.D. 4
5. Ketonemia, ketonuria and ketosis
• Ketonemia - increased concentration of ketone bodies in blood
• Ketonuria- Excess excretion of ketone bodies in urine
• Ketosis- Excess ketogenesis with impact on various organ functions
2/20/2017 Namrata Chhabra, M.D. 5
6. What is the significance of ketone bodies ?
Ketone bodies serve as a fuel for extra hepatic tissues.
• Liver can synthesize but cannot utilize the ketone bodies
• Brain can utilize but cannot synthesize the ketone bodies
• Brain utilizes ketone bodies only under conditions of glucose
deprivation
2/20/2017 Namrata Chhabra, M.D. 6
7. Ketogenesis
Ketogenesis takes place in liver using Acetyl co A as a substrate or a
precursor molecule.
Enzymes responsible for ketone body formation are associated
mainly with the mitochondria
2/20/2017 Namrata Chhabra, M.D. 7
8. Steps of ketogenesis
Step-1:
Two molecules of acetyl CoA condense to form Acetoacetyl CoA.
This reaction, which is catalyzed by Thiolase, is the reverse of the
thiolysis step in the oxidation of fatty acids.
2/20/2017 Namrata Chhabra, M.D. 8
9. Ketogenesis
Step-2:
Acetoacetyl CoA then reacts with acetyl CoA and water to give 3-hydroxy-3-
methylglutaryl CoA (HMG-CoA) and CoASH.
The reaction is catalyzed by HMG co A synthase.
This enzyme is exclusively present in liver mitochondria.
There are two iso-forms of this enzyme-cytosolic and mitochondrial.
The mitochondrial enzyme is needed for ketogenesis while the cytosolic form
is associated with cholesterol biosynthesis.
2/20/2017 9Namrata Chhabra, M.D.
11. Ketogenesis
Both enzymes(HMG CoA Synthase and HMG Co A Lyase) must be present in
mitochondria for ketogenesis to take place.
This occurs solely in liver.
The other two ketone bodies-Acetone and D(-)- 3-Hydroxybutyrate are formed
from Acetoacetate, the primary ketone body.
112/20/2017 Namrata Chhabra, M.D.
12. Formation of Acetone
• Acetone is formed by decarboxylation in the
presence of decarboxylase enzyme and,
because it is a beta-keto acid, acetoacetate
also undergoes a slow, spontaneous
decarboxylation to acetone.
• The odor of acetone may be detected in the
breath of a person who has a high level of
acetoacetate in the blood.
• “Acetone-breath” has been used
as a crude method
of diagnosing individuals with untreated
Type I diabetes mellitus.
2/20/2017 12Namrata Chhabra, M.D.
13. Formation of β-Hydroxy Butyrate
D (-)-3-Hydroxybutyrate (β-Hydroxy Butyrate) is formed by the
reduction of acetoacetate in the mitochondrial matrix by D(-)3-
hydroxybutyrate dehydrogenase.
D(-)-3-Hydroxybutyrate is quantitatively the predominant ketone
body present in the blood and urine in ketosis.
The ratio of β hydroxybutyrate to acetoacetate depends on the
NADH/NAD+ ratio inside mitochondria.
If NADH concentration is high, the liver releases a higher proportion
of β-hydroxybutyrate.
2/20/2017 13Namrata Chhabra, M.D.
14. Ketolysis
• Ketone bodies are utilized by extrahepatic tissues via a series of
cytosolic reactions that are essentially a reversal of ketone body
synthesis,
• Thus, the ketones must be reconverted to acetyl CoA in the
mitochondria.
2/20/2017 Namrata Chhabra, M.D. 14
15. Steps of ketolysis
Utilization of Beta-hydroxybutyrate
1) Beta-hydroxybutyrate, is first oxidized to acetoacetate with the
production of one NADH (1).
2) Under conditions where tissues are utilizing ketones for energy
production their NAD+/NADH ratios are going to be relatively high,
thus driving the β-hydroxybutyrate dehydrogenase catalyzed
reaction in the direction of acetoacetate synthesis.
2/20/2017 Namrata Chhabra, M.D. 15
16. Utilization of ketone bodies
2) Utilization of Acetoacetate-
Coenzyme A must be added to the acetoacetate.
The thioester bond is a high energy bond, so ATP equivalents must
be used.
In this case the energy comes from a trans esterification of the
CoASH from Succinyl CoA to acetoacetate by Coenzyme A transferase,
also called Succinyl co A : Acetoacetate co A transferase, also known
as Thiophorase.
2/20/2017 16Namrata Chhabra, M.D.
17. Utilization of Acetoacetate
The Succinyl CoA comes from the TCA cycle.
This reaction bypasses the Succinyl CoA synthetase step of the TCA
cycle,
hence there is no GTP formation at this steps although it does not
alter the amount of carbon in the cycle.
2/20/2017 Namrata Chhabra, M.D. 17
18. Utilization of ketone bodies
The liver has acetoacetate available to supply to other organs because it
lacks the particular CoA transferase and that is the reason that “Ketone
bodies are synthesized in the liver but utilized in the peripheral tissues”.
182/20/2017 Namrata Chhabra, M.D.
19. Liver v/s Peripheral tissues for ketones as fuel
molecules
• The enzyme, Succniyl co A Acetoacetate co A transferase, also
known as Thiophorase, is present at high levels in most tissues
except the liver.
• Importantly, 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,
and
• Also, lack of this enzyme in the liver prevents the futile cycle of
synthesis and breakdown of acetoacetate.
2/20/2017 19Namrata Chhabra, M.D.
20. Regulation of Ketosis
Ketogenesis is regulated at three steps-
1) Lipolysis in Adipose tissue
Ketosis does not occur unless there is an
increase in the level of circulating free
fatty acids that arise from lipolysis of
triacylglycerol in adipose tissue.
When glucose levels fall, lipolysis
induced by glucagon secretion causes
increased hepatic ketogenesis due to
increased substrate (free fatty acids)
delivery from adipose tissue.
Conversely, insulin, released in the well-
fed state, inhibits ketogenesis via the
triggering dephosphorylation and
inactivation of adipose tissue hormone
sensitive lipase (HSL).
20
2/20/2017 Namrata Chhabra, M.D.
21. Regulation of Ketosis
2) Fate of fatty acid-free fatty acids are either oxidized to CO2 or
ketone bodies or esterified to triacylglycerol and phospholipids.
There is regulation of entry of fatty acids into the oxidative pathway
by carnitine Acyl transferase-I (CAT-I)
Malonyl-CoA, the initial intermediate in fatty acid biosynthesis
formed by acetyl-CoA carboxylase in the fed state, is a potent
inhibitor of CAT-I .
Under these conditions, free fatty acids enter the liver cell in low
concentrations and are nearly all esterified to acylglycerols and
transported out of the liver in very low density lipoproteins (VLDL).
2/20/2017 21Namrata Chhabra, M.D.
22. Regulation of Ketosis
3) Fate of Acetyl co A
The acetyl-CoA formed in beta-oxidation is oxidized in the citric
acid cycle, or it enters the pathway of ketogenesis to form ketone
bodies.
As the level of serum free fatty acids is raised, proportionately
more free fatty acids are converted to ketone bodies and less
are oxidized via the citric acid cycle to CO2.
Entry of acetyl CoA into the citric acid cycle depends on the
availability of Oxaloacetate for the formation of citrate, but the
concentration of Oxaloacetate is lowered if carbohydrate is
unavailable or improperly utilized.
2/20/2017 22Namrata Chhabra, M.D.
24. 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. 242/20/2017 Namrata Chhabra, M.D.
25. Biological significance of ketone bodies
Ketone bodies serve as a fuel for extra hepatic tissues
Brain
It is metabolically active and metabolically privileged.
The brain generally uses 60-70% of total body glucose requirements, and
always requires some glucose for normal functioning.
Under most conditions, glucose is essentially the sole energy source of
the brain.
The brain cannot use fatty acids as they cannot cross the blood-
brain barrier.
As glucose availability decreases, the brain is forced to use either amino
acids or ketone bodies for fuel.
2/20/2017 25Namrata Chhabra, M.D.
26. Biological significance of ketone bodies
Acetoacetate and β-hydroxybutyrate are normal fuels of respiration and
are quantitatively important as sources of energy.
Heart muscle and the renal cortex use acetoacetate in preference to
glucose.
In contrast, the brain adapts to the utilization of acetoacetate during
starvation and diabetes.
In prolonged starvation,75% of the fuel needs of the brain are met by
ketone bodies.
Individuals eating diets extremely high in fat and low in carbohydrate, or
starving, or suffering from a severe lack of insulin (Type I
diabetes mellitus) therefore increase the synthesis and utilization of
ketone bodies
2/20/2017 26Namrata Chhabra, M.D.
27. Ketonemia
• Ketonemia - increased concentration of ketone bodies in blood
• It is due to increased production of ketone bodies by the liver
rather than to a deficiency in their utilization by extra hepatic
tissues.
• The production of ketone bodies occurs at a relatively low rate
during normal feeding and under conditions of normal
physiological status.
• Normal physiological responses to carbohydrate shortages cause
the liver to increase the production of ketone bodies from the
acetyl-CoA generated from fatty acid oxidation.
2/20/2017 27Namrata Chhabra, M.D.
28. Causes of Ketosis
Uncontrolled diabetes mellitus
Starvation
Chronic alcoholism
Von- Gierke’s disease
Heavy exercise
Low carbohydrate diet- For weight loss
Glycogen storage disease type 6(Due to phosphorylase kinase
deficiency)
Pyruvate carboxylase deficiency
2/20/2017 28Namrata Chhabra, M.D.
29. Causes of Ketosis
Prolonged ether anesthesia
Toxemia of pregnancy
Certain conditions of alkalosis
Nonpathologic forms of ketosis are found under conditions of high-
fat feeding and
After severe exercise in the post absorptive state.
2/20/2017 29Namrata Chhabra, M.D.
30. Summary
• The ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone)
are formed in hepatic mitochondria when there is a high rate of fatty
acid oxidation.
• The pathway of ketogenesis involves synthesis and breakdown of 3-
hydroxy-3-methylglutaryl-CoA (HMG-CoA) by two key enzymes, HMG-
CoA synthase and HMG-CoA lyase.
2/20/2017 30Namrata Chhabra, M.D.