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Hepatic  -Cystathionase Deficiency in Patients With AIDS
To the Editor: Patients infected with the human immunodeficiency virus (HIV) exhibit low plasma cysteine levels at all stages of the disease.1 Glutathione (GSH) levels are also reduced in plasma, T lymphocytes, erythrocytes, and lung epithelial-lining fluid in patients with HIV infection.2-3
Most circulating GSH is synthesized in the liver where L-cysteine concentration is a rate-limiting factor. The liver obtains most of its cysteine from L-methionine through the trans-sulfuration pathway, which involves  -cystathionase activity. Jahoor et al3 reported that the low GSH levels found in erythrocytes from HIV-infected subjects are due, at least in part, to a diminished availability of L-cysteine.3 However, the cause of this cysteine deficiency is not clear.
Methods
We followed the method described by Sturman et al4 to measure -cystathionase activity in liver samples obtained from autopsies of 3 men with the acquired immunodeficiency syndrome (AIDS) and 6 healthy men (17-44 years old) who died in automobile crashes. The first patient with AIDS was 27 years old and died of multiple organ failure and Pneumocystis carinii bronchopneumonia; the second patient was 38 years old and died of cytomegalovirus pneumonia and gastric hemorrhage; and the third patient was 59 years old and died of generalized Kaposi sarcoma.
Results
We found that -cystathionase activity was substantially reduced in the liver samples of the 3 men with AIDS compared with the 6 control subjects (Figure 1).
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Figure. -Cystathionase Activity in Liver Samples From Patients With the Acquired Immunodeficiency Syndrome (AIDS) and Healthy Controls
Results are expressed as mean (± SD). There were 3 samples from the patients with AIDS and 6 samples from the healthy controls. Difference between the groups was significant at P<.01.
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Comment
Reduced -cystathionase activity would be expected to result in low L-cysteine and GSH levels. Consequently, our results may help explain why AIDS is associated with a systemic deficiency of GSH and also provide a rationale for treating patients with AIDS with N-acetyl cysteine, which is a source of L-cysteine that is independent of the trans-sulfuration pathway.
We reported previously that inhibition of -cystathionase causes high rates of proteolysis in animals.5 The findings reported herein may provide a partial explanation for the increased proteolysis and cachexia that occurs in AIDS. Moreover, the very low -cystathionase activity renders L-cysteine an essential amino acid for patients with AIDS.
AUTHOR INFORMATION
Funding/Support: This work was supported by a grant from Conselleria de Sanitat of Generalitat Valenciana to Dr Viña.
José Antonio Martin, PhD;
Juan Sastre, PhD;
José García de la Asunción, MD,PhD;
Federico V. Pallardó, MD,PhD;
José Viña, MD,PhD
Departamento de Fisiología
Universidad de Valencia
Valencia, Spain
1. Droge W, Schulze-Osthoff K, Mihm S, et al. Functions of glutathione and glutathione disulfide in immunology and immunopathology. FASEB J. 1994;8:1131-1138.
ABSTRACT
2. Staal FJ, Ela SW, Roederer M, Anderson MT, Herzenberg LA, Herzenberg LA. Glutathione deficiency and human immunodeficiency virus infection. Lancet. 1992;339:909-912.
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3. Jahoor F, Jackson A, Gazzard B, et al. Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate. Am J Physiol. 1999;276:E205-E211.
4. Sturman JA, Gaull G, Raiha NCR. Absence of cystathionase in human fetal liver: is cystine essential? Science. 1970;169:74-76.
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5. Triguero A, Barber T, García C, Puertes IR, Sastre J, Viña JR. Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats. Br J Nutr. 1997;78:823-831.
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Letters Section Editors: Stephen J. Lurie, MD, PhD, Senior Editor; Jody W. Zylke, MD, Contributing Editor.
JAMA. 2001;285:1444-1445.
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