(2) Ketone Bodies

Excess — can be used to synthesize ketone bodies via ketogenesis

acetyl coA

Where does ketogenesis occur?

liver mitochondria

Two different sources of acetyl CoA in the body

pyruvate dehydration or beta oxidation

Where does acetyl CoA come from during a fasting state?

beta oxidation

Where does acetyl CoA come from during fed state?

pyruvate dehydrogenase reaction

Acetyl CoA has a great concentration in a (fed or fasting ) state

fasting

Show the ketone bodies, their names and how they may be converted between one another

Ketogenesis occurs during (an extended fast or a large meal)

extended fast

What can cause excess lipolysis?

fasting, prolonged exercise and low exercise levels

How does excess lipolysis result in ketogenesis?

it creates and overflow of acetyl coA as beta oxidation degrade fatty acids produced by lipolysis

Excess lipolysis results in what 2 outcomes?

ketogenesis in the liver and slowing of Krebs’ cycle as it is inhibited by high [NADH] and [Acetyl-CoA]

Ketogenesis

the synthesis/ production of ketone bodies. 2 acetyl-CoA are synthesized into acetoacetyl-CoA which is then converted to acetoacetate.

Ketone bodies stimulate — secretion which attenuates lipolysis. How does this hormone inhibit lipolysis?

insulin; it inhibits ATGL and HSL as well as increase malonyl-CoA levels which inhibits FA uptake into mitochondria and thus decreases beta oxidation

Show the feedback loop that ketone bodies are involved in within the image

The ketone body/insulin feedback loop is impaired in —--. Why?

type 1 diabetes due to issues with insulin production

Fatty acids and ketone bodies stimulate — secretion after (a few days of fasting or a large meal)

insulin; few days of fasting

What is the purpose of the ketone feedback loop?

prevents ketoacidosis, thus ensuring ketone bodies are only used as a fuel without causing damage to the organism

Ketogenic diets

low CHO diet. The body produces lots of ketone bodies as lipolysis proceeds rapidly. Based on the belief that the body will burn fat in the absence of carbs. Usually happens within 2 to 3 days of stopping carb intake. Limits carb intake to 20 g/day

Ketolysis

ketone body oxidation. Metabolic process of breaking down ketone bodies (beta-hydroxybutyrate and acetoacetate) into acetyl CoA to produce energy (ATP) in extrahepatic tissues

Ketone bodies are used in ketolysis in what cell types

brain, heart, skeletal muscle, and kidneys

Ketone bodies are NOT used in what cell types?

liver and RBCs

The brain (can or cannot) use ketone bodies

can

In a fed state, the brain gets –% of its energy from glucose and –% from ketone bodies. In a fasting state, it gets –% of energy from glucose and –% from ketone bodies

100 and 0; 25 and 75

t/f acetyl-CoA can be used a C-skeleton for glucose in the liver

false

Glucose sparing

phenomenon during which metabolic conditions degrade a large quantity of fatty acids via beta oxidation and high ketolysis inhibit glucose degradation, thereby contributing to glucose-sparing effect essential for brain survival during starvation.

Ketosis

physiological state of increased production of ketone bodies (typically occur 2-3 days after fasting/starving).

Ketosis represses —- by secreting —-, restoring homeostasis. Therefore it is not pathogenic to the body

lipolysis; insulin

Ketosis occurs sooner in people who consume very few —

carbs

Ketosis may be pathogenic under what conditions?

patients who have impaired glucose production from glycogen (e.g. glycogen storage diseases) or who have impaired gluconeogenesis

Ketoacidosis

dangerous, life-threatening pathological state in which ketone-overproductions exceed body’s ketone use. May cause depletion of blood [HCO3-] and blood acidification

Ketoacidosis manifests with very high rate of —- and —- is high

lipolysis and [ketone bodies] is high

Ketoacidosis is common seen with —-

insulin deficiency

Diabetic ketoacidosis

usually occurs in those with type 1 diabetes but is rare in type 2 diabetes. Characterized by extreme hyperglycemia, severe lack of insulin, high ketone level, low pH, low serum bicarbonate and dehydration

Diabetic ketoacidosis is the number — killer of children and adolescents with type 1 diabetes

1

If untreated, people with ketoacidosis can become —- and —-

unconscious and die

Ketostix

self-testing kit for detecting excess ketone bodies in urine

Small vs moderate vs large(high) concentration of ketone bodies in blood

Ketotic hypoglycemia

characterized by low blood glucose and high blood ketones

Possible causes of Ketotic hypoglycemia

prolonged fasting, metabolic disorders (diminished gluconeogenesis, impaired glycogen synthesis or degradation), diabetic over-injecting insulin, and/or ketogenic diet

Symptoms of Ketotic hypoglycemia

shakiness/trembling, confusion or lethargy, seizures, nausea, vomiting, abdominal pain, fruity smelling breath

Remedy for Ketotic hypoglycemia

immediate glucose administration

Non-ketoic (or hypo-ketotic) hypoglycemia

characterized by both low blood glucose and low blood ketones

Possible causes of non-Ketotic hypoglycemia

excess of drugs that stimulate insulin secretion, presence of insulinoma (pancreas tumors that over-secrete insulin), fatty acid oxidation disorder, and glycogen storage disorder type 1 (GSD 1)

Symptoms of non-Ketotic hypoglycemia

shaking, tremors, sweating, hunger, headache, dizziness, fatigue, irritability, vision changes, confusion, and heart palpitations

Remedy for non-Ketotic hypoglycemia

eating small meals every 3 hours to prevent blood sugar levels from dropping too low. Implant pumps that inject glucose constantly