Superactive insulin: (B10-aspartic acid)insulin(human)
The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, (Asp/sup B10/) insulin, corresponding to the mutant proinsulin and evaluated its biological activity. (Asp/sup B10/) Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone.
- Research Organization:
- City Univ. of New York, NY (USA)
- OSTI ID:
- 7143351
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:18
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
INSULIN
AMINO ACID SEQUENCE
BIOSYNTHESIS
CONFIGURATION INTERACTION
RECEPTORS
ASPARTIC ACID
CELL MEMBRANES
GENE MUTATIONS
GLUCOSE
HEREDITARY DISEASES
HISTIDINE
IODINE 125
LIQUID COLUMN CHROMATOGRAPHY
LIVER
RATS
THIN-LAYER CHROMATOGRAPHY
TRITIUM COMPOUNDS
ALDEHYDES
AMINO ACIDS
ANIMALS
AZOLES
BETA DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HEXOSES
HORMONES
IMIDAZOLES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
MOLECULAR STRUCTURE
MONOSACCHARIDES
MUTATIONS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PROTEINS
RADIOISOTOPES
RODENTS
SACCHARIDES
SEPARATION PROCESSES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques