The effect of coenzyme A and structurally related thiols on the mammalian fatty acid synthetase

A comparison was made of the structural features of thiol compounds which can interact with the mammalian fatty acid synthetase. Three functional characteristics were examined: (i) the ability of the free thiols, at low concentrations, to satisfy the essential thiol requirement of the enzyme, (ii) the ability of the free thiols, at higher concentrations, to inhibit enzyme activity, and (iii) the ability of the malonyl esters of these thiol compounds to act as substrates for fatty acid synthesis. The relative effectiveness of the various thiols studied was identical in all three roles. Coenzyme A and N-hexanoylcysteamine were the most effective, pantetheine and N-butyrylcysteamine were less effective, and N-acetylcysteamine was totally ineffective. These results lend strong support to our hypothesis (A. Stern, B. Sedgwick, and S. Smith, 1982, J. Biol. Chem.257, 799–803) that the various effects of CoA and structurally related thiols are localized at one and the same site, namely, the site of transfer of substrates between coenzyme A ester form and enzyme-bound form.     

Wood duck hatch date: relationship to pairing chronology, plasma luteinizing hormone, and steroid hormones during autumn and winter

We examined variation in courtship activity and hormone levels of male and female wood ducks (Aix sponsa) in relation to hatch date. Young wood ducks were assigned in groups of 8 (4 males and 4 females) to 4 experimental pens; 2 pens contained early-hatched ducks (3-12 April) and 2 pens contained late-hatched ducks (7-16 June). Courtship behaviors occurred less frequently in October and November than in December and January-February for both early- and late-hatched groups. Early-hatched wood ducks participated in courtship more frequently and formed pair bonds sooner than late-hatched individuals. Testosterone (T) and androstenedione (AD) levels of males did not differ between treatment groups; however, average levels of luteinizing hormone (LH) were greater for early-hatched males. Differences in LH occurred in 2 of 12 samples (6 October and 3 November); otherwise, LH did not vary by treatment. Levels of T and LH in males varied temporally, but there was no significant temporal variation in AE levels. Temporal variation in hormone levels was similar for early- and late-hatched males. Estradiol (E), progesterone (P), and LH levels of females did not differ between treatment groups. There was temporal variation in levels of E and LH, but not of P; this variation was similar for early- and late-hatched females. These data indicate that behavioral differences occurring temporally and between early- and late-hatched wood ducks were not related to corresponding differences in hormone levels.     

Gelation of liposome interior. A novel method for drug encapsulation.

Liposomes can be loaded with weak acids and bases, which exist in solutions in equilibrium with membrane permeable uncharged form, using various gradients across their membranes. Because in some cases the estimated drug concentration in the loaded liposomes exceeds their aqueous solubility we investigated the physical state of the liposome encapsulated anticancer drug Doxorubicin. X-Ray diffraction, electron microscopy, and test tube solubility experiments have shown that upon encapsulation the drug molecules form a gel-like phase.     

Fecundity of Euphausia lucens (Hansen) - laboratory evidence for multiple broods

There has been much controversy in the past as to how many broods euphausiids are capable of producing per season. Several authors have suggested that multiple broods are possible, although this has not been demonstrated in the laboratory. In the present study, two Euphausia lucens females were shown to spawn continuously over a period of at least 2.5 months. The euphausiids produced ≈ 33–40 broods during this period, representing 134–192% of their body carbon. Daily egg production rates varied from 0 to 86 eggs, representing a mean of 3–4% of their body carbon d⁻¹. Egg production rates were often severely depressed during moulting, and were also somewhat lower during experimental manipulation (changing food conditions). The results suggest that egg production by E. lucens, and perhaps by many other euphausiid species, are considerably higher than was previously thought.     

Clustering of lipid-bound annexin V may explain its anticoagulant effect.

In 1985 we isolated a new vascular anticoagulant protein VAC alpha, now called annexin V, with a high binding affinity (Kd less than 10(-10) M) for phospholipids. Its anticoagulant effect was attributed to displacement of coagulation factors from the phospholipid membrane. The present study demonstrates that the inhibition of prothrombinase activity by annexin V strongly depends on the curvature of the membrane surface and on the calcium concentration. Half-maximal inhibition of prothrombinase on and binding of annexin V to small vesicles, composed of 20% phosphatidylserine and 80% phosphatidylcholine, requires 2-3 mM calcium. With large vesicles and planar bilayers considerably less calcium is required for inhibition of prothrombinase and for lipid binding. Half-maximal binding of annexin V to large vesicles and to planar bilayers occurs at 0.7 and 0.2 mM calcium, respectively. This seemingly confirms the displacement model. The displacement of coagulation factors, however, proved to be incomplete, with residual surface concentrations of factors Xa, Va, and prothrombin sufficient for effective production of thrombin. Cryoelectron microscopy revealed that annexin V binding to large vesicles caused planar facets, indicating the formation of large sheets of clustered annexin V. Apparently, the formation of these two-dimensional arrays is promoted by calcium and hampered by high surface curvature. It is speculated that the complete inhibition (greater than 99%) of prothrombinase activity by annexin V is caused by the reduced lateral mobility of prothrombin and factor Xa in rigid sheets of annexin V covering the membrane.