FETAL BRANCHED CHAIN AMINO ACID AND KETO-ACID METABOLISM

  • Liechty, Edward, (PI)

Project: Research project

Description

During maternal fasting changes in ovine fetal metabolism occur such that
the fetus becomes less reliant on maternally acquired glucose and
increasingly reliant on amino acids as an energy source. Placental and
hind limb balance studies indicate that the branched chain amino acids may
be of central importance to the fetus during fasting. Thus, the proposed
investigation will characterize the ovine fetus utilization of the branched
chain amino acids and their alpha keto analogues. Utilizing the chronic
fetal lamb preparation the following specific questions will be addressed. 1. Does the fetal hind limb utilize completely it's large uptake of
branched chain amino acids or are significant quantities of the
alpha-ketoacids given off for inter-organ transport? Quantitative balance
studies for glucose, lactate, pyruvate, amino acids and branch chain
alpha-ketoacids will be determined across the fetal hind limb in fed and
fasted animals. 2. How does maternal fasting effect fetal tissue distribution and degree
of activity of the enzymes responsible for degradation of the branched
chain amino acids? Tissue samples from the in vivo preparations will be
obtained from fetal skeletal muscle, liver, kidney, heart, adipose tissue
and brain as well as placenta and maternal skeletal muscle and liver.
These samples will be assayed for branched chain aminotransferase activity,
branched chain keto acid dehydrogenase activity and pyruvate dehydrogenase
activity; phosphorylated and non-phosphorylated forms will be quantitated
for the latter two enzymes. 3. What is the placental balance of branched chain alpha-ketoacids? Do
changes in fetal branched chain amino acid carbon and nitrogen utilization
correlate with changes in fetal glucose carbon utilization? Ovine
placental balance of the alpha-ketoacids as well as other substrates
mentioned above will be quantitated in the fed and fasting state. In
addition, using radioactive and stable isotope techniques, fetal glucose
carbon and branched chain amino acid carbon utilization will be determined
simultaneously in both a fed and fasting state. In summary, the proposed research will characterize alterations in fetal
branched chain amino acid metabolism as the fetus adapts to a diminished
maternal nutrient supply.
StatusFinished
Effective start/end date8/1/845/31/05

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $314,389.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $307,336.00
  • National Institutes of Health
  • National Institutes of Health: $315,468.00
  • National Institutes of Health: $299,443.00
  • National Institutes of Health: $295,564.00
  • National Institutes of Health
  • National Institutes of Health: $118,722.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Branched Chain Amino Acids
Keto Acids
Fetus
Insulin-Like Growth Factor I
Insulin
Amino Acids
Glucose
Fasting
Proteolysis
Fetal Development
Fetal Proteins
Leucine
Sheep
Mothers
Ubiquitin
Proteins
Malnutrition
Carbon
Extremities
Somatomedins

Keywords

  • Medicine(all)