BIOGENESIS AND STRUCTURE OF GLYCOGEN

Project: Research project

Description

This proposal is a continuation of a long-term study of the
structure of mammalian glycogen and how this giant molecule
originates in the cell. We have evidence that in rabbit muscle the
glycogen is convalently bound at two points to a protein (we call
the latter glycogenin) which we believe is the biosynthetic origin
of the molecule, i.e. glycogen is constructed on glycogenin as a
post-translational event to the synthesis of the protein. Our
evidence for the linkage between glycogen and glycogenin is that
it is a new type of carbohydrate to protein bond, involving
tyrosine, through its hydroxyl group. Insulin, with its still
unexplained ability to promote glycogen synthesis in muscle, acts
on its receptor so as to cause the latter to become an active
kinase which proceeds to phosphorylate itself and other cell
proteins at the tyrosine hydroxyl group. The connection between
tyrosine phosphorylation and the construction of glycogen on a
tyrosine residue may provide a clue to how insulin stimulates
glycogen synthesis. The discovery of glycogenin may also have
wider utility in explaining how other storage polysaccharides
originate. Another structural featrue of muscle and liver glycogen that we
have defined in some detail is the occurrence of two types of
phosphate ester. Some glucose residues carry a 6-phosphate
group. Others carry what appears to be a phosphodiester. We will further investigate the glycogen-protein bond, seeking
additional evidence for the involvement of tyrosine. Then we will
determine the peptide sequences of muscle glycogenin in the
regions where it is joined to glycogen and determine the precise
structure of the glycogen around the linkage to protein. Similar,
less-detailed studies will be made for glycogens and starches from
other sources. We will attempt in muscle to detect and
characterize the enzyme(s) that synthesize the protein to
carbohydrate linkage. We will determine the nature of the
phosphodiester and the location of the phospho-esters in the
glycogen molecule as well as exploring the enzymic mechanisms
whereby they are incorporated into glycogen. We will prepare and
use antibodies to locate glycogenin muscle and other sources of
glycogen. We will use the immature frog oocyte for in vivo
studies of the synthesis of glycogenin and glycogen as well as the
incorporation of phosphate esters.
StatusFinished
Effective start/end date5/1/878/31/99

Funding

  • National Institutes of Health: $206,287.00
  • National Institutes of Health: $208,384.00
  • National Institutes of Health: $203,644.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $210,551.00
  • National Institutes of Health
  • National Institutes of Health: $220,842.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Glycogen
Muscles
Proteins
Esters
Tyrosine
Hydroxyl Radical
glycogenin
Oocytes
Insulin
Glycogen Synthase
Anura
Liver Glycogen
Phosphorylation
Enzymes
Glucose
Starch

ASJC

  • Medicine(all)