Hypoglycemia Gluconeogenesis

Glucagon is secreted as a response to hypoglycemia and activates both glycogenolysis and gluconeogenesis in the liver, causing release of glucose into the blood. 

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. 

Most patients with pyruvate-carboxylase deficiency present with failure to thrive, developmental delay, recurrent seizures and metabolic acidosis. Lactate, pyruvate, alanine, [3-hydroxybutyrate and acetoacetate concentrations are elevated in blood and urine. Hypoglycemia is not a consistent finding despite the fact that pyruvate carboxylase is the first rate-limiting step in gluconeogenesis. 

Alcoholics are very susceptible to hypoglycemia. In addition to poor nutrition and the fact that alcohol is metaboUzed to acetate (acetyl CoA), the high amounts of cytoplasmic NADH formed by alcohol dehydrogenase and acetaldehyde dehydrogenase interfere with gluconeogenesis. High NADH favors the formation ofi... 

The answer is B. While all of the listed conditions are consistent with lethargy and developmental defects, the lactic acidosis rules out pyruvate kinase deficiency. Thiamine and niacin deficiencies are unlikely due to the lack of effect of vitamin supplementation. Excess pyruvate is the source of the elevated alanine in the serum. The clinical findings are thus consistent with pyruvate carboxylase deficiency, which is associated with severe hypoglycemia due to fasting due to impaired gluconeogenesis. 

Individuals with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. The metabolic derangements caused by metabolism of large amounts of ethanol can result in hypoglycemia, as a result of impaired hepatic gluconeogenesis, and in ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

The consumption and subsequent metabolism of ethanol inhibits gluconeogenesis, leading to hypoglycemia in individuals with depleted stores of glycogen. Alcohol consumption can also increase the risk for hypoglycemia in patients using insulin. 

The release of insulin is closely coupled with the glucose level. Hypoglycemia results in a low level of insulin and a high level of glucagon and, hence, favors the processes of glycogenolysis and gluconeogenesis. 

Subsequent studies have shown (e.g. 5,6, Table I) that the liver of newborns is indeed deficient in enzymes needed not only for drug metabolism but also for the elimination of natural products. For example, because of the lack of UDP-glucuronyl transferase resulting in the inability to dispose of bilirubin, the newborn is at risk for brain damage by kernicterus. That PEP carboxykinase, the key catalyst of gluconeogenesis de novo is absent at 7 months and still at low titers 3 days after birth (Table I), probably contributes to the fact that transient hypoglycemia (which can also cause brain damage) represents a hazard to full term as well as premature infants. The immaturity of the hepatic enzyme composition imposes limitations on the choice of nutrients used to supplement or re-... 

Answer The first step in the synthesis of glucose from lactate in the liver is oxidation of the lactate to pyruvate like the oxidation of ethanol to acetaldehyde, this requires NAD+. Consumption of alcohol forces a competition for NAD+ between ethanol metabolism and gluconeogenesis, reducing the conversion of lactate to glucose and resulting in hypoglycemia. The problem is compounded by strenuous exercise and lack of food because at these times the level of blood glucose is already low. 

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