Chloride transporter protein, defective

The primary structure refers to the amino acid sequence of the polypeptide chain. An error caused by a single incorrect amino acid amongst a chain of 1480 amino acids can seriously affect the function of the protein. This happens in people with cystic fibrosis who have a defective CFTR (cystic fibrosis transmembrane conductance regulator) gene, which produces a defective chloride transporter protein. In 70% of people with cystic fibrosis, the mutation is deletion of 3 base pairs in the DNA, which results in the loss of phenylalanine... 

Cystic fibrosis—a fatal, hereditary disease characterized by a heavy mucus buildup in the lungs—is caused by a defective plasma membrane protein. In persons with cystic fibrosis this transport protein, known as the sodium-potassium pump, abnormally transports sodium ions across the membrane without carrying the chloride ions that usually accompany them. Research is currently underway to correct through genetic engineering the faulty gene that codes for the plasma membrane protein. 

ABC transporters are involved in the transport of a wide variety of molecules. For example, cystic fibrosis is caused by a defective ABC transporter for chloride ion (cystic fibrosis transmembrane regulator. Chapter 12) and in Tangier s disease, the abnormality of cholesterol efflux is due to defects in an ABC protein (Chapter 20). 

Cystic fibrosis is the most common lethal autosomal recessive disease affecting the Caucasian population. It has a frequency of approximately 1 in 2500 and a carrier frequency of approximately 1 in 25. The protein affected is the cystic fibrosis transmembrane conductance regulator (CFTR), which is a chloride ion channel. There are over 1000 mutations that have been discovered in the CFTR gene and over 80 percent of these mutations lead to disease. The mutations lead to (1) defective or decreased protein production, (2) defective processing of the protein, (3) protein that is defective in the regulation of the chloride channel, or (4) defect in the transport of chloride ions. The most common mutation, a deletion of a phenylalanine residue at amino acid position 508 (AFjog), results in misfolding of the protein it consequently does not traffic to the membrane. 

Cystinuria is the prototype of a number of inborn errors of metabolism believed to result from the deficiency of carrier proteins involved in transporting molecules through the cell membrane. Transport defects in kidney, intestine, or both have also been described for other amino acids— glycine, cystine, tryptophan, methionine—for glucose and galactose, and even for electrolytes such as calcium, chloride, and sodium [173]. Some of these inborn errors are described in other chapters. 

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