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DENTAL BIOCHEMISTRY 2015 LECTURE 10 GLUCONEOGENESIS

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DENTAL BIOCHEMISTRY 2015 LECTURE 10 GLUCONEOGENESIS Michael Lea Lecture Outline Function of gluconeogenesis and tissue distribution Reaction sequence Rate-limiting ... – PowerPoint PPT presentation

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Title: DENTAL BIOCHEMISTRY 2015 LECTURE 10 GLUCONEOGENESIS


1
DENTAL BIOCHEMISTRY 2015LECTURE
10GLUCONEOGENESIS
  • Michael Lea

2
Lecture Outline
  • Function of gluconeogenesis and tissue
    distribution
  • Reaction sequence
  • Rate-limiting steps
  • Energy requirement
  • Substrates and regulation of gluconeogenesis
  • Suggested reading Lippincotts Biochemistry, 6th
    edition, pages 117-123

3
Function of gluconeogenesis and tissue
distribution
  • Gluconeogenesis is the synthesis of glucose from
    three carbon precursors including lactate,
    pyruvate and glycerol
  • Gluconeogenesis occurs in the liver and kidney

4
Reaction sequence
  • The conversion of pyruvate to glucose occurs in a
    series of eleven reactions.
  • Seven of the reactions are catalyzed by enzymes
    that are also used in glycolysis.
  • The conversion of pyruvate to phosphenolpyruvate
    occurs in two steps catalyzed by pyruvate
    carboxylase and phosphoenolpyruvate
    carboxykinase.
  • Two specific phosphatases catalyze the hydrolysis
    of fructose 1,6-bisphosphate and glucose
    6-phosphate.

5
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8
Rate-limiting Steps in Gluconeogenesis
  • Hormonal and dietary regulation is exerted on the
    enzymes whose function is restricted to
    gluconeogenesis pyruvate carboxylase,
    phosphoenolpyruvate carboxykinase, fructose
    1,6-bisphosphatase and glucose 6-phosphatase.
  • Activation of pyruvate carboxylase by acetyl
    coenzyme A is an important regulatory mechanism.

9
Energy Requirement
  • The conversion of two moles of pyruvate to one
    mole of glucose requires the equivalent of 6
    moles of ATP and two moles of NADH.

10
ADP ATP
X
11
Substrates for Gluconeogenesis
  • Major substrates include lactate, pyruvate and
    glycerol.
  • Most amino acids can be metabolized to form
    precursors for gluconeogenesis.

12
Reciprocal Control of Glycolysis and
Gluconeogenesis
  • Insulin increases glycolysis and decreases
    gluconeogenesis
  • Glucocorticoids and glucagon increase
    gluconeogenesis and decrease glycolysis.

13
Reciprocal Control of Glycolysis and
Gluconeogenesis by Fructose 2,6-bisphosphate
  • Fructose 2,6-bisphosphate (F26BP) is a switch
    molecule that increases glycolysis by activating
    phosphofructokinase 1 and inhibiting fructose
    1,6-bisphosphatase.
  • F26BP levels are controlled by an enzyme with 2
    active sites. The un-phosphorylated enzyme has
    phosphofructokinase 2 activity and yields F26BP.
    The phosphorylated enzyme has fructose
    2,6-bisphosphatase activity and lowers the
    concentration of F26BP.

14
ATP
ADP
X
X
15
Gluconeogenesis and Diabetes
  • In diabetes mellitus there is impaired uptake of
    glucose, particularly in muscle and adipose
    tissue.
  • The body responds as in starvation with an
    increase in gluconeogenesis. This results in a
    further elevation of blood glucose levels that
    may exceed the renal glucose threshold resulting
    in significant glucose in urine.

16
Lecture Objectives
  • After studying this lecture material you should
    be able to
  • Describe the function of gluconeogenesis
  • Identify where gluconeogenesis occurs
  • Distinguish the enzyme catalyzed reactions common
    to glycolysis and gluconeogenesis and those
    unique to gluconeogenesis
  • Identify the energy requirement for
    gluconeogenesis
  • Describe the substrates and regulation of
    gluconeogenesis
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