Lecture 13 Gluconeogenesis Overview

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What is gluconeogenesis?

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  • The synthesis of glucose from simpler precursors like pyruvate and lactate.

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Which tissues rely heavily on glucose?

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  • Brain, erythrocytes, kidneys, embryonic tissues.

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50 Terms

1
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What is gluconeogenesis?

  • The synthesis of glucose from simpler precursors like pyruvate and lactate.

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Which tissues rely heavily on glucose?

  • Brain, erythrocytes, kidneys, embryonic tissues.

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Where does gluconeogenesis primarily occur in mammals?

  • In the liver.

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How many glycolysis enzymes are shared by gluconeogenesis?

  • Seven out of ten.

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How does gluconeogenesis bypass the three irreversible steps of glycolysis?

  • By using energetically favorable reactions.

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What is the main energy source for the brain?

Glucose

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What is the key precursor molecule for gluconeogenesis?

Pyruvate

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Which enzyme converts pyruvate to oxaloacetate?

  • Pyruvate carboxylase.

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Why can't oxaloacetate be directly transported from mitochondria to the cytosol?

  • Mitochondria lack an oxaloacetate transporter.

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Which enzyme converts malate back to oxaloacetate in the cytosol?

Malate dehydrogenase.

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What is the first bypass in gluconeogenesis?

Conversion of pyruvate to phosphoenolpyruvate (PEP) via oxaloacetate.

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Which amino acids are glucogenic?

Amino acids that can be converted into glucose via the citric acid cycle.

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Can mammals convert fatty acids to glucose?

No, except for glycerol.

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What is reciprocal regulation?

The mechanism that prevents glycolysis and gluconeogenesis from occurring simultaneously.

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What pathway allows plants and microorganisms to convert fatty acids to glucose?

The glyoxylate pathway.

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Which enzymes are involved in the reciprocal regulation of glycolysis and gluconeogenesis?

Phosphofructokinase-1 (PFK-1) and fructose 1,6-bisphosphatase (FBPase-1).

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Which hexokinase is not inhibited by glucose-6-phosphate?

Hexokinase IV (glucokinase).

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Where is glucokinase primarily found?

Liver, pancreas, hypothalamus, and small intestine.

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How does ATP affect phosphofructokinase-1 (PFK-1)?

ATP inhibits PFK-1 by binding to an allosteric site.

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What molecule relieves ATP inhibition of PFK-1?

AMP and ADP

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What is the role of citrate in regulating glycolysis?

Citrate inhibits PFK-1, signaling that the cell's energy needs are being met.

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What does high AMP inhibit in gluconeogenesis?

Fructose bisphosphatase-1 (FBPase-1).

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What signals low blood glucose levels to stimulate gluconeogenesis?

Glucagon.

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What does insulin do to gluconeogenesis?

Inhibits it.

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What happens to blood glucose levels in diabetes mellitus?

They are elevated.

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Which type of diabetes involves autoimmune destruction of pancreatic beta cells?

Type 1 diabetes.

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Which gene is the strongest genetic risk factor for Type 2 diabetes?

TCF7L2 gene.

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What is hemoglobin A1c (HbA1c)?

A measure of blood glucose control over a period of 120 days.

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What happens when acetyl-CoA accumulates from fatty acid breakdown?

It signals to stop glucose oxidation and stimulates gluconeogenesis.

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What hormone promotes glucose uptake and storage in cells?

Insulin.

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What is the effect of fructose 2,6-bisphosphate on PFK-1?

It increases PFK-1's affinity for fructose 6-phosphate.

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What is the effect of fructose 2,6-bisphosphate on FBPase-1?

It reduces FBPase-1’s affinity for its substrate.

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How does glucagon affect fructose 2,6-bisphosphate levels?

Glucagon lowers its levels, inhibiting glycolysis and stimulating gluconeogenesis.

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How does insulin affect fructose 2,6-bisphosphate levels?

Insulin increases its levels, stimulating glycolysis and inhibiting gluconeogenesis.

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What is the main hormonal signal for gluconeogenesis during fasting?

Glucagon.

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How many bypass reactions occur in gluconeogenesis?

Three.

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Why is gluconeogenesis considered energetically expensive?

It requires a significant input of ATP and GTP to convert pyruvate to glucose.

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Which enzyme converts pyruvate to phosphoenolpyruvate (PEP)?

Phosphoenolpyruvate carboxykinase (PEPCK).

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Which tissues cannot utilize fats for energy and depend on glucose?

Brain and erythrocytes.

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What is the role of pyruvate carboxylase in gluconeogenesis?

It catalyzes the conversion of pyruvate to oxaloacetate

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Which molecule allosterically stimulates pyruvate carboxylase?

Acetyl-CoA.

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How does high ATP affect gluconeogenesis?

It stimulates gluconeogenesis by slowing down glycolysis.

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What is the effect of insulin on gluconeogenesis-related gene transcription?

Insulin regulates the transcription of more than 150 genes related to gluconeogenesis.

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What can diabetic ketoacidosis result from?

Insufficient insulin, causing the body to break down fats and produce ketones.

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What is the function of glucose 6-phosphatase in gluconeogenesis?

It catalyzes the final step, converting glucose 6-phosphate to free glucose.

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Which molecule is an indicator of low energy levels in the cell?

AMP.

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How does acetyl-CoA affect pyruvate dehydrogenase?

It allosterically inhibits pyruvate dehydrogenase, reducing glucose oxidation.

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What is the role of metformin in Type 2 diabetes treatment?

It lowers blood glucose by reducing gluconeogenesis in the liver.

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What is the consequence of high blood glucose in diabetes mellitus?

Damage to blood vessels and tissues, potentially leading to complications like kidney failure or blindness

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What does insulin promote besides glucose uptake?

Glycogen storage and fat synthesis.