Leif B. Sorensen

Origin and Extrarenal Elimination of Uric Acid in Man

The origin of uric acid, metabolic pathways of purine metabolism and the disposition of uric acid in normal man are reviewed. Two thirds of the uric acid is normally excreted through the kidney while one third gains entrance to the gut where it undergoes uricolysis. The pathogenesis of hyperuricemia in primary and secondary gout is discussed. Increased production or decreased excretion of uric acid are the two principal mechanisms of hyperuricemia. The known biochemical defects associated with primary overproduction gout are outlined. Extrarenal uricolysis assumes a greater role when the renal excretion of uric acid is compromised.

Diminished Renal Urate Secretion Per Nephron As a Basis for Primary Gout

Abstract In order to examine the role of the kidney in the pathogenesis of primary gout, the rate of uric acid turnover and renal transport were studied in 15 gouty patients. Uric acid turnover dat...

Guanosine 5′-phosphate reductase of human erythrocytes

Abstract 1. 1. Human GMP-reductase [NADPH: GMP oxidoreductase (deaminating), EC 1.6.6.8] was purified from erythrocytes with a yield of 15% and a 1200-fold increase in specific activity. 2. 2. The apparent K m for NADPH and GMP is 8.5·10 −6 and 4.9·10 −6 M, respectively. 1 molecule of IMP is formed for every molecule of NADPH oxidized to NADP + . 3. 3. The purified enzyme exhibits a rather sharp maximum of activity around pH 7.5 and is relatively thermostable, losing only 40% of its activity after heating at 67 °C for 15 min. 4. 4. A sulfhydryl donor is not an absolute requirement for the enzymatic reaction. However, activity was decreased to 50% of normal when a sulfhydryl compound was omitted from the reaction mixture. 5. 5. XMP is a potent inhibitor of GMP-reductase. The inhibition by XMP is competitive for GMP bindign by the enzyme with a K i = 1.1·10 −6 M. The enzyme was also inhibited by all divalent metal ions tested.

Cutaneous Immunofluorescence Studies to Adult Rheumatoid Arthritis in Sun‐exposed and Non‐sun‐exposed Areas

ABSTRACT: The incidence and significance of positive cutaneous immunofluorescence findings were assessed in biopsy specimens of both sun‐exposed and non‐sun‐exposed skin of 34 adult patients with rheumatoid arthritis (RA) who were not receiving systemic corticosteroids. The incidence of lupus erythomatosus (LE)‐band was low (8.6%) in both groups. Twenty‐eight percent of the patients had perivascular IgM and lor C3 deposits, and 74% had cytoid bodies in the papillary dermis. These studies indicate that the incidence of LE band is low in RA and that the detection of such a band in normal skin warrants close follow‐up of RA patients for possible development of LE.

Urate transporters: transforming the face of hyperuricemia and gout.

> …the causes which predispose to gout…are either such as produce an increased formation of uric acid in the system, or which lead to its retention in the blood. > > — A.B. Garrod, 1863 1 Although some readers of The Journal may find the September article by Torres, et al 2 a challenge, we believe the effort to persevere will be well worth it. This is because the report nicely illustrates how the burgeoning field of analysis of common variants in gene sequences (polymorphisms), when combined with scrupulous attention to the clinical characteristics of affected patients, can simplify and extend understanding of complicated disease mechanisms and, potentially, contribute to more informed clinical evaluation and management decisions. The disease at issue here is gout, an inflammatory metabolic disorder afflicting over 8 million of the estimated 40 million hyperuricemic American adults. Before discussing the Torres, et al report2, we present an historical overview of the pathogenesis of hyperuricemia and gout, with the aim of providing a context for work described therein. That hyperuricemia is a necessary, but not sufficient, risk factor for gout was postulated in 1859 and 1863 by A.B. Garrod1, who also proposed that crystals of “urate of soda” deposited in tissues were the cause of gouty inflammation and could remain for protracted periods, causing local destruction (tophaceous gout). An additional remarkable insight was that “…the kidneys are implicated in gout, probably in its early, but certainly in its chronic stages, and the renal affection, perhaps only functional at first, subsequently becomes structural….” As affirmed above, Garrod also clearly recognized the distinction between gout arising from uric acid overproduction and from impaired uric acid elimination. Garrod’s exposition of the hyperuricemia, urate crystal deposition, and acute and chronic inflammation pathogenetic triad in gout was verified and extended over the next century, particularly in the … Address correspondence to Dr. Becker, 237 East Delaware Place, Chicago, IL 60637-1713, USA. E-mail: becker{at}medicine.bsd.uchicago.edu

RECENT ADVANCES IN STUDY OF URIC ACID METABOLISM AND GOUT.

Increased understanding of the pathogenesis of acute gout has developed in the past few years. Investigators have indicated that an attack is precipitated by (1) deposition of sodium urate crystals, (2) development of an inflammatory reaction against these crystals, and (3) propagation of the inflammatory response by addition of more crystals to inflamed area.The nature of the inborn metabolic errors of primary gout is still obscure. Studies point to a dual cause of the hyperuricemia. Until more evidence is accumulated, it seems useful to separate patients into two categories: those with overproduction and those with normal production of uric acid.