We review the relationship between various types of mitochondrial DNA mutations and the prevalence as well as the pathobiochemical and clinical features of mitochondrial diabetes mellitus. An A to G transversion mutation in the tRNA(Leu(UUR)) gene is associated with diabetes in about 1.5% of the diabetic population in different countries and races. Phenotypically this type of mitochondrial diabetes is combined with deafness in more than 60% and is clinically distinguishable with respect to several characteristics from the two idiopathic forms of diabetes. The underlying pathomechanism is probably a delayed insulin secretion due to an impaired mitochondrial ATP production in consequence of the mtDNA defect.

Summary: a-and γ-enolase isoenzyme substance concentrations were measured in serum and plasma from healthy subjects and from 174 patients with different solid tumours. While α-enolase was found to be increased in the plasma of patients with tumours of quite different origin, γ-enolase apparently reflected malignancies of the neuroendocrine System. Before the beginning of the cytotoxic therapy γ-enolase was increased above the upper limit of the reference r nge (10 μg/l) in 27/27 patients (100%) suffering from small cell lung cancer. Most patients with squamous cell carcinoma of the lung or with prostatic cancer exhibited normal γ-enolase, while both tumour types produced high plasma substance concentrations of the aisoenzymes of enolase. Wertigkeit der Enolase-Isoenzyme als TumormarkerZusammenfassung: Die Substanzkonzentrationen von a-und γ-Enolase-Isoenzym wurden im Serum und Plasma von Gesunden und 174 Patienten mit unterschiedlichen, soliden Tumoren bestimmt. W hrend sich die α-Enolase-Formen als relativ unspezifisch, d. h. bei unterschiedlichen Tumoren im Plasma erh ht fanden, zeigten die γ-Isoenzyme maligne Erkrankungen des neuroendokrinen Systems relativ spezifisch an. Bei einem Kollektiv von 27 Patienten mit kleinzelligem Lungen-Karzinom fand sich vor der Therapie in 100% der F lle ein Anstieg der γ-Enolase ber den oberen Referenzwert (10 Hg/l). Patienten mit Plattenepithel-Karzinom der Lunge und solche mit Prostata-Karzinomen hatten in der Regel normale γ-Enolase-, dagegen erh hte aEnolase-Substanzkonzentrationen im Plasma. Introdiictionstudied and characterized by Marangos* group (2). Cells related to the amine precursor uptake and de-Recently it was found that small cell lung carcinoma carboxylation (APUD) System (1) share several com-cells also express APUD ceU-specific markers such s mon properties, which include the ability to produce bombesin, L-dopa decarboxylase and γ-enolase (3). and secrete peptides, the presence of storage vesicles The first report by Carney et al. (4) that γ-enolase is and a similar enzyine and isoenzyme pattern. One of elevated to a high degree in the serum of most small the marker proteinsforthis System is the γ-isoenzyme cell lung cancer patients was confirmed by others of enolase (neuron-specific enolase, NSE) extensively (5 -14), but it became evident that patients suffering

The mitochondrial DNA (mtDNA) of Japanese patients suffering from the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) exhibits a specific heteroplasmic A----G transition in the tRNA(Leu) at position 3243. In this study, we investigated mtDNA from skeletal muscle, cardiac muscle, brain, liver, diaphragm, fibroblasts and blood cells of four Caucasians with MELAS, one younger healthy sister of two MELAS patients, and eleven controls. We found that 1) the mutation was present in all investigated tissues of Caucasians with MELAS but not in controls, 2) within a single patient, the tissue-specific variation of the copy number of mutated mtDNA covered the same range as in the skeletal muscle of different patients, 3) the mutation was also present in the blood cells of the healthy sister of two MELAS siblings.

Carboxymethylation of lysine residues has been shown to result from oxidation of glycated proteins in vivo and in vitro leading to an augmentation of proteins' net negative charge. The metabolism of carboxymethylated low density lipoprotein (LDL) was studied in cultured human fibroblasts and mouse peritoneal macrophages. In vitro carboxymethylation was achieved by incubation of LDL with glyoxylic acid in the presence of Na(CN)BH3. Carboxymethylation inhibited metabolism of LDL via the high affinity receptor in fibroblasts as did methylation. The uptake of LDL into mouse peritoneal macrophages via the scavenger receptor, which was stimulated by acetylation, was not affected.

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