Welcome to the first lecture in Leaning Unit 3 where you will learn about the importance of nutrients in animal life I am Dr Peter Ferket and this lecture is about disorders and unique aspects of energy metabolism In the previous lectures of unit 1 and 2 you learned about what is normal about digestive physiology how nutrients are absorbed and metabolized and ending with energy metabolism In this lecture you will learn about some of the things that can go wrong in energy metabolism and how to avoid them 1 A number of metabolic disorders have their basis in disturbances related to energy metabolism As indicated in the figures to the right some of these disorders are associated with mitochondrial function or problem with cellular nutrition that results in premature cell death or apoptosis These metabolic disorders include ketosis diabetes and metabolic syndrome Other disorders of energy metabolism affect undesirable outcomes such as Obesity Poor quality of life Chronic illness and Shortened lifespan I will begin with ketosis in ruminants Ketosis is a metabolic disease in which excessive quantities of ketone bodies are produced It commonly occurs in starvation when body lipid is mobilized and is a frequent condition in domestic ruminants twin lamb disease or pregnancy paralysis in sheep ketosis and downer cow syndrome in dairy cattle A critical factor in the development of ketosis is insufficiency of glucose for brain metabolism which results in confusion and often immobility Below is a picture of twin lamb disease where the ewe is laying on her side and can t get up In the middle is a pregnant goat with pregnancy paralysis Next is a cow with ketosis 6 weeks post calving Note the poor body condition of this cow On the lower right is a cow just after calving that is down otherwise known as downer cow syndrome in dairy cattle Why does ketosis occur in ruminants more frequently in non ruminants Glucose is specifically required as an energy source by some tissues For example the brain and central nervous system require glucose although ketone bodies can be used to some extent The energy requirement of the brain under normal circumstances is met almost entirely from the metabolism of glucose The blood brain barrier limits the penetration of large molecules like lipids into the brain to use as an energy source The brain depends on glucose to meet its very high energy needs Ketosis in dairy cattle generally occurs during the early stage of lactation when cows are in a negative energy balance Inciting factors include an inadequate post parturient feed intake high milk production and mobilization of body lipid to sustain energy needs especially in cows with high body fat Ruminants do not absorb much carbohydrate yielding glucose from the digestive tract because most almost all of it is fermented by the rumen microbiota Moreover there is a lack of carbohydrate precursors such as propionate and amino acids for incorporation of fats as acetyl CoA into the citric acid cycle so ketone bodies are produced at greater rates than in normal states Ketosis is often secondary to other disorders that depress feed intake Insufficient feed intake is one of the root causes of ketosis Illustrated here is a schematic flow chart of how insufficient feed intake may lead to ketosis If feed intake does not meet the energy demand there is not enough ruminal production of propionic acid by the rumen microbiota Propionate is a precursor of glucose through gluconeogenesis Insufficient glucose causes hypoglycemia or low blood sugar which forces the cow to metabolize fatty acids and glycerol that are oxidized to form Acetyl CoA Because of the low feed energy intake relative to demand the liver cannot cope with all that access Acetyl CoA So that excess acetyl CoA is then converted to ketone bodies acetoacetate and beta hydroxybutyrate which accumulate and causes ketosis and associated symptoms A cow with ketosis excretes ketone bodies in urine and through the milk giving it an off flavor Diabetic people and animals are also susceptible to ketosis but for a different reason Diabetics are not able to metabolize glucose because of a lack of insulin or insulin resistance which forces their cells to catabolize fat which yields excessive ketone bodies Diabetes mellitus is a metabolic disorder characterized by elevated concentrations of blood glucose hyper glycaemia Diabetes is from a Greek word referring to excessive urination and mellitus from Greek word referring to sugar in urine There are four major categories of diabetes i Type 1 ii Type 2 iii gestational and iv secondary diabetes As I will discuss in more detail type 1 and type 2 diabetes are the major diabetic disorders but Type 2 is the most common form of diabetes accounting for 90 95 of the diabetics in the USA Gestational diabetes can develop during pregnancy in women who don t already have diabetes and it usually goes away after the baby is born Up to 10 of pregnancies in the US are affected by gestational diabetes mostly in overweight women and can be managed until a successful delivery Secondary diabetes results as a consequence of another medical condition endocrine disease or hereditary disease The illustration to the right depicts the symptoms of Type 1 and Type 2 diabetes how they differ and how they have similar symptoms 7 I will first talk about Type 1 Diabetes This type occurs most often during childhood and was formerly called juvenile onset diabetes or insulin dependent diabetes mellitus Type 1 diabetes is an autoimmune disorder where the immune system produces antibodies that attack and destroy the insulin producing beta cells of the pancreas The loss of beta cells results in a lack of insulin production leading to the onset of the signs of diabetes The symptoms of Type 1 diabetes include extreme thirst hunger frequent urination and fatigue All of these symptoms are a result of elevated blood glucose Click on this link in your notes to view an overview of Type 1 diabetes by a Mayo Clinic expert 8 In contrast to Type 1 diabetes where it develops during childhood and the patient cannot produce enough insulin from the pancreas type 2 diabetes occurs most frequently in middle aged or older adults Most people with this condition have normal or above normal concentrations of blood insulin but their body s cells cannot respond to insulin signals as they should Insulin functions in the transfer of glucose across cell membranes Insulin binds to insulin