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Gluconeogenesis and Diff BW Gluconeogenesis and Glycolysis

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21 views16 pages

Gluconeogenesis and Diff BW Gluconeogenesis and Glycolysis

Uploaded by

nimrasiddiqui2004
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Biochemistry

Gluconeogenesis
Dr Tehniat Faraz
Learning objectives
• Define gluconeogenesis
• Outline the steps of Gluconeogenesis
• Understand the differences between glycolysis and gluconeogenesis
• Outline the irreversible steps of glycolysis
• Understand how the irreversible steps are bypassed in
gluconeogenesis
Definitions
Glycolysis is the set of reactions that oxidize glucose into two pyruvate
molecules

Gluconeogenesis is the synthesis of glucose from non-carbohydrate


molecules
Gluconeogenesis
• During fasting, the liver maintains glucose levels in blood through
glycogenolysis or gluconeogenesis.
• These pathways are promoted by glucagon and epinephrine and
inhibited by insulin.
• In fasting, glycogen reserves drop dramatically in the first 12
hours, during which time gluconeogenesis increases.
• After 24 hours, it represents the sole source of glucose.
• Gluconeogenesis requires expenditure of ATP that is provided by
β-oxidation of fatty acids.
• Therefore, hepatic gluconeogenesis is always dependent on β-
oxidation of fatty acids in the liver.
Substrates for Gluconeogenesis
• Glycerol 3-phosphate (from triacylglycerol in adipose)
• Lactate (from anaerobic glycolysis)
• Propionyl CoA (from odd number carbon fatty acids)
• Gluconeogenic amino acids (protein from muscle)
• TCA intermediates (citrate, isocitrate,α-ketoglutarate,
succinyl co-A, succinate, fumarate and malate)
Gluconeogene
sis
Regulation by Acetyl CoA
• Pyruvate carboxylase and pyruvate dehydrogenase are
both regulated by acetyl-CoA.
• In the well-fed, absorptive state (insulin), accumulating
acetyl-CoA is shuttled into the cytoplasm for fatty acid
synthesis.
• Between meals, when fatty acids are oxidized in the
liver for energy, accumulating acetyl-CoA activates
pyruvate carboxylase and gluconeogenesis and inhibits
PDH
Cori’s Cycle
• During fasting, lactate from red blood cells (and
possibly exercising skeletal muscle) is converted
in the liver to glucose that can be returned to the
red blood cell or muscle.
• This is called the Cori cycle.
Differences Between
Glycolysis and
Gluconeogenesis
Glycolysis Catabolic reaction
Net ATP production

Gluconeogenesis Anabolic reaction


Net ATP consumption
Substrates
Glycolysis glucose

Gluconeogenesis
• Glycerol 3-phosphate (from triacylglycerol in adipose)
• Lactate (from anaerobic glycolysis)
• Gluconeogenic amino acids (protein from muscle)
• TCA intermediates
Location in the cell
Glycolysis Cytoplasm

Gluconeogenesis Mitochondria and Cytoplasm


Regulation
Gluconeogenesis

Glycolysis

Promoted by Promoted by
Ingestion of glucose Fasting
Higher ADP/ATP ratio Higher AMP/ADP ratio
Insulin Glucagon and epinephrine
Enzymes involved
References
• Harper’s illustrated Biochemistry, 31st ed, Victor W. Rodwell
• USMLE Step 1 Lecture Notes (Kaplan) 2018: Biochemistry and Medical Genetics,
Sam Turco

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