A7 gluconeogenesis

What is the chemical logic of glycolysis and gluconeogenesis?

Glycolysis releases energy by oxidizing glucose to pyruvate

gluconeogenesis synthesizes glucose from non-carbohydrate precursors to maintain blood glucose levels.

Glycolysis

Produce ATP and pyruvate for energy and biosynthetic precursors.

Gluconeogenesis

Generate glucose for tissues when dietary glucose is low.

Glycogen metabolism

Store (glycogen synthesis) and mobilize (glycogen breakdown) glucose.

How are glycolysis and gluconeogenesis regulated to prevent futile cycling?

Through reciprocal regulation by allosteric effectors, hormones (insulin, glucagon), and key enzymes (PFK-1, FBPase-1, pyruvate kinase).

What is the Warburg effect?

Tumor cells prefer high glycolysis with lactate fermentation even under aerobic conditions; basis for PET tumor scans.

What is the fate of pyruvate under aerobic vs anaerobic conditions?

• Aerobic: Enters mitochondria → TCA cycle.

  • Anaerobic/fast metabolism: Converted to lactate.

What is the Cori cycle?

Lactate from muscle is sent to the liver, converted back to glucose, and returned to muscle.

What is the glucose-alanine cycle?

Muscle degrades protein → alanine (via transamination) → liver → pyruvate → glucose synthesis.

How does adipose tissue contribute to gluconeogenesis?

Supplies glycerol from triglyceride breakdown.

Describe the first bypass reaction (pyruvate to PEP).

• Pyruvate carboxylase (mitochondrial, requires biotin + ATP, activated by acetyl-CoA) converts pyruvate → oxaloacetate.

• PEPCK (cytosolic or mitochondrial, requires GTP) converts oxaloacetate → PEP.

  • Oxaloacetate is shuttled as malate to the cytosol before conversion.

Which enzyme deficiency corrected by biotin supplementation causes hypoglycemia?

Pyruvate carboxylase.

Describe the second bypass reaction.

FBPase-1 hydrolyzes fructose 1,6-bisphosphate → fructose 6-phosphate; irreversible, highly exergonic.

Describe the third bypass reaction.

Glucose 6-phosphatase in ER of liver/kidney converts glucose 6-phosphate → glucose; allows glucose release into blood.

What is the overall reaction of gluconeogenesis from pyruvate?

2 Pyruvate + 4 ATP + 2 GTP + 2 NADH → Glucose + 4 ADP + 2 GDP + 2 NAD+ + 6 Pi

Why is gluconeogenesis considered energetically expensive?

It consumes ATP, GTP, and NADH to produce glucose, preventing futile cycling with glycolysis.