Starvation ketosis

Addition of ethyl acetate to a specimen having a transaminase activity of 47 units was responsible for the following increases in enzyme activity 10 mg/100 ml, 60 units 20 mg/100 ml, 77 units 40 mg/100 ml, 107 units and 80 mg/100 ml, 150 units. Transaminase activity in these specimens determined by another method ranged from 32 to 34 units (C7). Thus, when serum from patients with ketosis is assayed for aspartate aminotransferase activity by the diazo method, false elevations of activity may be recorded due to reaction of acetoacetic acid. In Table 11 are shown some values obtained by the diazo method and by an ultraviolet NADH NAD aspartate aminotransferase technique (B12). Examination of the medical records of these patients indicated that they were either diabetics who were in ketosis or individuals who were eating very poorly and had some degree of starvation ketosis. Similar elevations have been observed in patients receiving p-aminosalicylic acid (G6). 

The three compounds, acetoacetate, acetone, and 3-hydroxybutyrate, are known as ketone bodies.60b The inability of the animal body to form the glucose precursors, pyruvate or oxaloacetate, from acetyl units sometimes causes severe metabolic problems. The condition known as ketosis, in which excessive amounts of ketone bodies are present in the blood, develops when too much acetyl-CoA is produced and its combustion in the critic acid cycle is slow. Ketosis often develops in patients with Type I diabetes mellitus (Box 17-G), in anyone with high fevers, and during starvation. Ketosis is dangerous, if severe, because formation of ketone bodies produces hydrogen ions (Eq. 17-5) and acidifies the blood. Thousands of young persons with insulin-dependent diabetes die annually from ketoacidosis. 

Uloodglucose eoiicenlration. This will be maintained even in the face of prolonged starvation. Ketosis develops during starvation and carbohydrate deficiency. Hyperglycacmia is frequently encountered as part of the metabolic response to injury. 

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

The basic form of ketosis occurs in starvation and involves depletion of available carbohydrate coupled with mobihzation of free fatty acids. This general pattern of metabohsm is exaggerated to produce the pathologic states found in diabetes meUitus, twin lamb disease, and ketosis in lactating catde. Nonpathologic forms of ketosis are found under conditions of high-fat... 

Ketosis is mild in starvation but severe in diabetes meUitus and ruminant ketosis. 

Ketosis, a metabohc adaptation to starvation, is exacerbated in pathologic conditions such as diabetes mellitus and ruminant ketosis. 

In the treatment of ketosis in starvation, diarrhoea, vomiting or high fever. 

Answer Lysine and leucine are exclusively ketogenic. These amino acids are degraded entirely to acetyl-CoA and acetoacetyl-CoA, and no parts of their carbon skeletons can be used for glucose synthesis. Leucine is especially common in proteins. Its degradation makes a substantial contribution to ketosis under starvation conditions. 

Direct Test on Urine Glucose, ketones, and pH— Labstix test Dip a Labstix strip briefly into the urine and read after 10 to 15 seconds. For glucose, the result should be correlated with blood-glucose determination. A positive result for ketones may indicate intoxication by acetone or isopropyl alcohol. This test may also be positive in starvation or in diabetic ketosis. 

Ketones commonly are elevated in the blood in states of starvation, as the body calls upon its fatty acids (stored as triglycerides) to break down and provide fuel. Ketones may also be elevated in diabetes mellicus, where glucose does not enter the cell and carmot be efficiently utilized. Triglycerides then break down to provide the fetty acids and acetyl CoA useful as fuel, sometimes with formation of ketones as well. In severe diabetic ketosis, one may actually detect the smell of acetone coming from the patient. 

The entire process of ketosis reversed by restoring an adequate level of carbohydrate metabolism. In starvation, restoration consists of adequate carbohydrate ingestion in diabetes melhtus, ketosis can be reversed by insulin administration, which permits circulating blood glucose to be taken up by the cells. With production of oxaioacetate, the... 

Ketosis can occur in starvation, in ethanol abuse, and following exercise, the last because of a switch in blood... 

Ketone body formation, which occurs within the matrix of liver mitochondria, begins with the condensation of two acetyl-CoAs to form acetoacetyl-CoA. Then acetoacetyl-CoA condenses with another acetyl-CoA to form /3-hydroxy-/3-methylglutaryl-CoA (HMG-CoA). In the next reaction, HMG-CoA is cleaved to form acetoacetate and acetyl-CoA. Acetoacetate is then reduced to form /3-hydroxybutyrate. Acetone is formed by the spontaneous decarboxylation of acetoacetate when the latter molecule s concentration is high. (This condition, referred to as ketosis, occurs in uncontrolled diabetes, a metabolic disease discussed in Special Interest Box 16.3, and during starvation. In both of these conditions there is a heavy reliance on fat stores and /3-oxidation of fatty acids to supply energy.)... 

Ketosis, abnormally high levels of blood ketone bodies, is a situation that arises under some pathological conditions, such as starvation, a diet that is extremely low in carbohydrates (as with the high-protein liquid diets), or uncontrolled diabetes mellitus. The carbohydrate intake of a diabetic is normal, but the carbohydrates cannot get into the cell to be used as fuel. Thus diabetes amounts to starvation in the midst of plenty. In diabetes the very high concentration of ketone acids in the blood leads to ketoacidosis. The ketone acids are relatively strong acids and therefore readily dissociate to release H+. Under these conditions the blood pH becomes acidic, which can lead to death. 

Drynan, L., Quant, P.A. Zammit, V.A. (1996) Biochem J311, 791-795 The role of changes in the sensitivity of hepatic mitochondrial overt carnitine palmitoyltransferase in determining the onset of the ketosis of starvation in the rat. 

Quantitative studies show that only a small fraction of the fatty acids are subject to co-oxidation in the liver under normal conditions [387]. Starvation, diabetes mellitus and ketosis apparently augment co-oxidation of fatty acids in experimental animals and man [388-390]. In these situations, several investigators estimated that 10-40% of the fatty acids may be initially co-oxidised [388,389,392]. The increase was probably not due to induction of the monooxygenase enzymes but could reflect a decreased rate of formation of fatty acid esters for reacylation [390]. However, monooxygenase metabolism of fatty acids is inducible. Treatment with pheno-barbital increased the hepatic co2-hydroxylation, while the col-hydroxylation of fatty acids was little affected [374]. Renal cortical hydroxylation of fatty acids could be induced by a high intake of fat in the diet [393]. 

Acetoacetate, p-hydroxybutyrate, and acetone are known as ketone bodies. They are synthesized in the liver from acetyl CoA. During starvation, in unchecked diabetes, and after excessive alcohol consumption, the level of ketone bodies becomes very high, leading to several conditions ketonemia, ketonuria, acetone breath, and ketosis. 

---