Integrated Metabolism During Starvation Lecture Notes PDF

Integrated metabolism during starvation  Definition of starvation Starvation is the deprivation of food, water and salts and may result from: 1. Inability to obtain food (during famine, ‫)مجاعه‬. 2. Desire to lose weight rapidly. 3. In clinical situations in which an individua...

Integrated metabolism during starvation  Definition of starvation Starvation is the deprivation of food, water and salts and may result from: 1. Inability to obtain food (during famine, ‫)مجاعه‬. 2. Desire to lose weight rapidly. 3. In clinical situations in which an individual can not eat because of brain trauma, burns… etc. 4. Political strike ‫اضراب سياسي‬. 5. Chronic anorexia, e.g., anorexia nervosa. The recorded time for a man survived while starved of food was 3 - 4 weeks but it may reach 9 - 10 weeks with large depot fat. The maximum starvation of water is 7 - 10 days and of salts is 2 weeks.  1. Role of the liver in metabolism during starvation (high glucagon /insulin ratio) : A) Carbohydrate metabolism: The liver maintains the blood glucose level firstly by increased glycogen degradation "glycogenolysis" and then by increased gluconeogenesis. Hepatic glycogenolysis is a transient response to early starvation as the liver glycogen exhausted after 8-12 hours of fasting. Gluconeogenesis starts 4-6 hours after the last meal and become fully activated as the liver stores of glycogen are depleted.  B) Fat metabolism: Increased fatty acid oxidation : – Oxidation of fatty acids derived from lipolysis of adipose tissue which is controlled by glucagons & catecholamines. Increased synthesis of ketone bodies: A. Mainly β-hydroxy butyric acid and start during the first day of starvation when the concentration of acetyl CoA produced from fatty acid oxidation exceeds the oxidative capacity of kreb's cycle as they used as fuel by most tissues including the brain. B. When the level of ketone bodies in the blood is sufficiently high , there will be no need for gluconeogenesis from amino acids and so decrease loss of essential proteins. C) Amino acid & protein metabolism: There is increased rate of amino acid degradation.  Role of the adipose tissue in metabolism during starvation: A) Carbohydrate metabolism: Low level of circulating insulin→ inhibition of glucose transport into the adipocytes thus decreases the fatty acid and TAGs synthesis. B) Fat metabolism: – Increased TAGs degradation : Decreased insulin & increased glucagon and catecholamines → activation (phosphorylation) of the hormone sensitive lipase and subsequently hydrolysis of the stored TAGs. – Increased release of fatty acids: Hydrolysis of the stored TAGs in the adipose tissue produces fatty acids that released in the blood where it binds to albumin and transported to various tissues for use as a fuel & glycerol that used as a gluconeogenic precursor by the liver.  Role of the skeletal muscles in metabolism during starvation: A) Carbohydrate metabolism: – Inhibition of glucose transport into muscles and its subsequent metabolism due to low levels of circulating insulin. B) Fat metabolism: During the first two weeks of starvation, muscles use fatty acids from the adipose tissue and ketone bodies from the liver as fuel. After that, muscles decrease their use of ketone bodies and oxidize fatty acids almost exclusively. This leads to a further increase in the already elevated level of circulating ketone bodies. C) Protein metabolism: During the first few days of starvation, there is a rapid breakdown of muscle protein providing amino acids that are used by the liver for gluconeogenesis. The loss in the tissue proteins differ according to the vitality of the organ , for example: – Brain loses 3% of its protein content. – Muscle loses 30 % of its protein content. – Liver loses 50% of its protein content. – Spleen loses 70% of its protein content. – Adipose tissue loses 100% of its protein content. This is mainly controlled by glucocorticoids. After several weeks of starvation, the rate of muscle breakdown decreased due to a decline in the need for glucose as a fuel for the brain and depends on the ketone bodies.  Role of the brain in metabolism during starvation During the first days of starvation, the brain continues to use glucose exclusively. Blood glucose is maintained by hepatic gluconeogenesis from the amino acids provided by the rapid breakdown of the muscle proteins. In prolonged starvation (>2-3 weeks) , plasma ketone bodies reached markedly elevated levels & are used as a fuel by the brain , this reduce the need for protein catabolism for gluconeogenesis.