In the area of sperm metabolism we will isolate larger quantities of the seminal vesicle protein that is a specific inhibitor of calcium transport in spermatozoa. Antibodies to this protein will be used to develop a radioimmunoassay for the inhibitor of calcium transport to determine whether this is a ubiquitous regulator of Ca++ fluxes or whether it is confined to seminal vesicles and seminal fluid. The relation of alkali metal ion fluxes to the acrosomal reaction of mammalian spermatozoa will be examined using a sensitive method developed by Dr. D. F. Babcock. The role of acetyl carnitine in supporting the enhanced motility associated with sperm capacitation will be examined. The role of ferroactivator-4 in the synthesis of carnitine in testis and other tissues will be studied in detail. In the area of carbonhydrate metabolism we will continue the search for possible """"""""second messengers"""""""" produced by the plasma membrane Alpha adrenergic receptor and those for vasopressin and angiotensin. The mechanism by which hepatocytes and perfused liver fail to respond to the """"""""hyperglycemic"""""""" effect of 3-aminopicolinate will be studied as well as the hyperglycemic effects of lergotrile and related drugs. In the area of metabolic regulation, ferroactivators 3 and 4 will be purified and characterized. The protein to which FA-4 is bound will be isolated and its role in the hydroxylation of trimethyllysine and butyrobetaine will be examined. Ferroactivator 2 will be isolated from dog liver and its role in regulating dog liver P-enolpyruvate carboxykinase (PEPCK) will be examined. The mobilization of Fe++ from mitochondria by cytosolic Ca++ will be investigated in more detail as will the amount and cellular distribution of iron in liver and kidney of normal rats in comparison with those afflicted with metabolic disorders such as Fe++ deficiency anemia, excess dietary iron, diabetes, etc. Our long-term goal is to learn the cause and to find a rational method for prevention or treatment of diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM010334-20
Application #
3150772
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1978-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
20
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Graduate Schools
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Kneer, N; Lardy, H (2000) Thyroid hormone and dehydroepiandrosterone permit gluconeogenic hormone responses in hepatocytes. Arch Biochem Biophys 375:145-53
Coronel, C E; Maldonado, C; Aoki, A et al. (1995) Electron microscopic immunolocalization of caltrin proteins in guinea pig seminal vesicles. Arch Androl 35:233-46
Battelli, D; Bellei, M; Kneer, N et al. (1994) Effects of dehydroepiandrosterone and carnitine treatment on rat liver. Biochem Mol Biol Int 33:1063-71
Bobyleva, V; Kneer, N; Bellei, M et al. (1993) Comparative studies of effects of dehydroepiandrosterone on rat and chicken liver. Comp Biochem Physiol B 105:643-7
Bobyleva, V; Kneer, N; Bellei, M et al. (1993) Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone. J Bioenerg Biomembr 25:313-21
Coronel, C E; Novella, M L; Winnica, D E et al. (1993) Isolation and characterization of a 54-kilodalton precursor of caltrin, the calcium transport inhibitor protein from seminal vesicles of the rat. Biol Reprod 48:1326-33
San Agustin, J T; Lardy, H A (1993) Lysogenic activity of enhancer caltrin and the influence of phospholipids on its expression. Biol Reprod 49:723-9
Nagdas, S K (1992) Effect of chlorpromazine on bovine sperm respiration. Arch Androl 28:195-200
Coronel, C E; Winnica, D E; Novella, M L et al. (1992) Purification, structure, and characterization of caltrin proteins from seminal vesicle of the rat and mouse. J Biol Chem 267:20909-15
Coronel, C E; Lardy, H A (1992) Functional properties of caltrin proteins from seminal vesicle of the guinea pig. Mol Reprod Dev 33:74-80

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