Glutamine deficiency

Glutamine deficiency occurs in critically ill patients, especially burn patients, as a result of increased protein turnover in the hypercatabolic state (56,57). Low levels of Glutamine on admission are associated with shock and increased hospital mortality and are more common in older persons (58). Glutamine supplementation in ICU patients was reviewed by the Italian Society of Enteral and Parenteral Nutrition (SINPE) (59), which noted that increased plasma glutamine levels were associated with improved outcomes in ICU patients. Other antioxidants such as parenteral selenium are also of interest in ICU patients (60). 

Hyperammonemia Type 2. A deficiency of ornithine transcarbamoylase (reaction 2, Figure 29-9) produces this X chromosome-linked deficiency. The mothers also exhibit hyperammonemia and an aversion to high-protein foods. Levels of glutamine are elevated in blood, cerebrospinal fluid, and urine, probably due to enhanced glutamine synthesis in response to elevated levels of tissue ammonia. 

An underweight 4-year-old boy presents semi-comatose in the emergency room at 10 a.m. Plasma glucose, urea, and glutamine are abnormally low acetoacetate is elevated and lactate is normal. He Is admitted to the ICU, where an increase in blood glucose was achieved by controlled infusion of glucagon or alanine. Which metabolic pathway is most likely deficient in this child ... 

IWo days after a full-term normal delivery, a neonate begins to hyperventilate, develops hypothermia and cerebral edema, and becomes comatose. Urinalysis reveals high levels of glutamine and orotic acid. The BUN is below normal. Which enzyme is most likely to be deficient in this child ... 

Orotic acid in the diet (usually at a concentration of 1 per cent) can induce a deficiency of adenine and pyridine nucleotides in rat liver (but not in mouse or chick liver). The consequence is to inhibit secretion of lipoprotein into the blood, followed by the depression of plasma lipids, then in the accumulation of triglycerides and cholesterol in the liver (fatty liver) [141 — 161], This effect is not prevented by folic acid, vitamin B12, choline, methionine or inositol [141, 144], but can be prevented or rapidly reversed by the addition of a small amount of adenine to the diets [146, 147, 149, 152, 162]. The action of orotic acid can also be inhibited by calcium lactate in combination with lactose [163]. It was originally believed that the adenine deficiency produced by orotic acid was caused by an inhibition of the reaction of PRPP with glutamine in the de novo purine synthesis, since large amounts of PRPP are utilized for the conversion of orotic acid to uridine-5 -phosphate. However, incorporation studies of glycine-1- C in livers of orotic acid-fed rats revealed that the inhibition is caused rather by a depletion of the PRPP available for reaction with glutamine than by an effect on the condensation itself [160]. 

FIGURE 18-14 Treatment for deficiencies in urea cycle enzymes. The aromatic acids benzoate and phenylbutyrate, administered in the diet, are metabolized and combine with glycine and glutamine, respectively. The products are excreted in the urine. Subsequent synthesis of glycine and glutamine to replenish the pool of these intermediates removes ammonia from the bloodstream. 

Choline deficiency developed in a 41-year-old woman with advanced cervical cancer who underwent prolonged parenteral nutrition (915). Her liver function tests became abnormal and she became jaundiced and complained of nausea and vomiting. The serum choline concentration was 5.77 mmol/1 and there was histological evidence of hepatic steatosis. There was steady improvement with oral choline supplementation, 3 g/ day, and with oral glutamine 15 g/day. There was a 45% improvement in serum choline concentration over baseline. 

Consideration of other plasma amino acids also informs the diagnosis of inborn errors of urea synthesis. The plasma concentrations of glutamine and alanine are often elevated in parallel with or prior to the ammonium concentration as they act as a nitrogen buffer. Plasma arginine concentrations are low since the only synthetic route for arginine in humans is via the urea cycle. In contrast, the arginine concentration is elevated in ARG-1 deficiency. Hyperornithinemia and homocitrullinuria are the characteristic features of the hyperammonemia, hyperornithinemia, and homocitrullinuria (HHH) syndrome caused by a defect in the ornithine transporter (ORNT-1). 

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