# GLUCOSE METABOLISM IN NEOPLASTIC TISSUES

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1992 · $177,132

## Abstract

The long term objective of this proposal is to understand the molecular
basis of the abnormal energy metabolism of many transformed cells, which is
characterized phenotypically by a high glucose catabolic rate.  The major
focus will be on the enzyme hexokinase which catalyzes the first and
committed step of glucose catabolism.  Significantly, hexokinase is
markedly elevated in many transformed cells where it targets mitochondrial
receptors.  Recent progress has shown that hexokinase is the only
glycolytic enzyme in tumor cells bound to the mitochondria, where it serves
to preferentially phosphorylate glucose with mitochondrially generated ATP
(Can. Res., 1988; JBC, 1988).  The purification of the tumor enzyme and its
mitochondrial receptor have been completed and a full-length cDNA of the
enzyme has been cloned, sequenced and overexpressed in active form in E.
coli (Biochem., 1986; Can. Res., 1988; JBC, 1990a, 1990b).  Some very
fundamental questions can now be addressed about the tumor hexokinase
molecule, its capacity for mitochondrial binding, and its high expression
during tumor cell growth.  Specific Aims are six-fold:

1.  To clearly define, using deletion analysis and synthetic     peptides,
those regions of the tumor hexokinase molecule     involved in
mitochondrial binding, catalysis, and regulation     by Glu-6-P.

2.  To identify, using random and site directed mutational     analysis,
those amino acids most critical for binding the     tumor hexokinase
molecule to the outer mitochondrial     membrane.

3.  To establish, using approaches outlined in "1" and "2" above,     the
relationship between that region of the tumor hexokinase     molecule
involved in membrane binding and that region     involved in ATP-dependent
enzyme release.

4.  To elucidate the molecular basis of the regulatory process in
transformed cells that is primarily responsible for the high     "net"
expression of the gene coding for mitochondrial     hexokinase.

5.  To determine to what extent tumor promoters and growth     regulators
induce normal cells to take on the cancer     phenotype in which hexokinase
levels, mitochondrial binding,     and high glucose catabolic rates
correlate.

6.  To elucidate the mechanism of the antitumor drug Lonidamine     which
inhibits mitochondrial bound hexokinase and glucose     catabolism in
certain tumor cell lines.

The proposed research is not only of fundamental significance to our
understanding of glucose catabolism and its regulation, in normal and
transformed cells, but may provide new insights into the design of
antitumor drugs that target energy metabolism.

## Key facts

- **NIH application ID:** 3170610
- **Project number:** 5R01CA032742-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** PETER L PEDERSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $177,132
- **Award type:** 5
- **Project period:** 1982-08-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170610

## Citation

> US National Institutes of Health, RePORTER application 3170610, GLUCOSE METABOLISM IN NEOPLASTIC TISSUES (5R01CA032742-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170610. Licensed CC0.

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