Gluconeogenesis Flashcards
what is the role of gluconeogenesis
synthesizing glucose from NON CARBOHYDRATE precursors
-lactate
-glycerol
-amino acids
where does gluconeogenesis occur
LIVER
-lesser extent in kidney
why is gluconeogenesis important for maintaining blood glucose level
provides adequate glucose to the brain, red blood cells, and renal medulla (primary fuel source)
What three glycolytic steps are bypassed during gluconeogenesis and why
-the IRREVERSIBLE steps of glycolysis are bypassed
- Hexokinase/glucokinase
- bypassed by glucose-6-phosphate - Phosphofructokinase- 1 (PFK-1)
-bypassed by fructose-1,6-bisphosphate - Pyruvate Kinase
(bypassed by pyruvate carboxylase and phosphoenolpyruvate carboxykinase)
-these steps are bypassed because they are highly EXERGONIC and UNIDIRECTIONAL under physiological conditions
what is the function of pyruvate carboxylase
-carboxylate= adds a carboxyl group (-COOH)
-which involves the fixation of a CO2 molecule
-requires an enzyme
-requires ATP
converts pyruvate to oxaloacetate
pyruvate + CO2 + ATP —>
Oxaloacetate + ADP +Pi
-MITOCHONDRIA
-requires biotin as a cofactor and is activated my acetyl-CoA
what is the function of phosphoenolpyruvate kinase (PEPCK)
converts oxaloacetate to phosphoenolpyruvate
-requires GTP (guanosine triphosphate)
-CYTOSOL or MITOCHONRDIA
what is the function of fructose 1,6- bisphosphoTASE
converts fructose- 1,6-bisphosphate to fructose-6-phosphate
what is the function of glucose-6-phophaTASE
converts glucose-6-phosphate to glucose
what are the net reactions of gluconeogenesis (reactants and products)
2 pyruvates + 4ATP + 2GTP +2NADH +6H2O –>
glucose + $ADP + 2 GDP + 6Pi + 2 NAD+
what are the key REGULATORY points of glyconeogensis
- Fructose-1,6-bisphosphatase: Inhibited by AMP and fructose-2,6-bisphosphate; activated by ATP.
- Pyruvate carboxylase: Activated by acetyl-CoA.
- PEPCK: Regulated at the transcriptional level by glucagon and cortisol
How does glucagon influence gluconeogensis
Glucagon increases gluconeogenesis by:
- Activating protein kinase A (PKA)—> decreases fructose-2,6-bisphosphate levels—> inhibition of fructose-1,6-bisphosphatase.
Upregulating PEPCK gene expression
What happens to gluconeogenesis during fasting or prolonged exercise?
Gluconeogenesis increases during fasting or prolonged exercise due to elevated levels of glucagon and cortisol, providing glucose to maintain blood glucose levels.
What are the major precursors for gluconeogensis
- Lactate
- Glycerol
- Amino Acids (Alanine)
when does lactate occur and where does it go as it relates to gluconeogenesis
Source: Produced during ANAEROBIC GLYCOLYSIS in tissues like skeletal muscle and red blood cells.
Conversion: Lactate is TRANSPORTED TO LIVER and converted to pyruvate by the enzyme lactate dehydrogenase (LDH).
Reaction:
Lactate + NAD⁺ → Pyruvate + NADH + H⁺
This process is part of the CORI CYCLE, which recycles lactate from peripheral tissues into glucose in the liver.
what is glycerol and where does it go as it relates to gluconeogenesis
Source: Derived from the breakdown of triglycerides (lipolysis) in adipose tissue.
Conversion:
Glycerol is phosphorylated by glycerol kinase to form glycerol-3-phosphate.
Reaction: Glycerol + ATP → Glycerol-3-phosphate + ADP
Glycerol-3-phosphate is oxidized by glycerol-3-phosphate dehydrogenase to form dihydroxyacetone phosphate (DHAP), an intermediate of gluconeogenesis and glycolysis.
Reaction: Glycerol-3-phosphate + NAD⁺ → DHAP + NADH + H⁺
what is an amino acid and where does it go as it relates to gluconeogenesis
Source: Released from muscle protein breakdown during fasting or starvation.
Conversion:
Alanine is converted to pyruvate by the enzyme alanine aminotransferase (ALT). This transamination reaction involves the transfer of an amino group to α-ketoglutarate, forming glutamate.
Reaction: Alanine + α-ketoglutarate → Pyruvate + Glutamate
Other glucogenic amino acids (e.g., glutamine, aspartate) are converted into TCA cycle intermediates like oxaloacetate or α-ketoglutarate, which feed into gluconeogenesis
What does phosphorylate mean
-phosphorylate (adding phosphate group (PO4 3-)
-catalyzed by enzymes (KINASES)
-A phosphate group is transferred, often from ATP (adenosine triphosphate)
Why can’t fatty acids be directly converted into glucose?
Fatty acids are metabolized to acetyl-CoA, which cannot be converted into pyruvate b/c the irreversible nature of the pyruvate dehydrogenase reaction.
However, odd-chain fatty acids produce propionyl-CoA, which can be converted into glucose.
How does alcohol consumption impair gluconeogenesis?
Alcohol metabolism increases NADH levels, shifting the equilibrium of key reactions (e.g., pyruvate to lactate and oxaloacetate to malate), thereby depleting precursors needed for gluconeogenesis.
What is oxidative phosphorylation?
Final step of cellular respiration, where the energy from high-energy electrons (carried by NADH and FADH₂) is used to produce ATP.
It occurs in the mitochondrial inner membrane and is the primary way cells generate energy in the presence of oxygen.
How does gluconeogenesis bypass the irreversible pyruvate kinase step of glycolysis?
2 STEPS
- Pyruvate –> Oxaloacetate
- pyruvate carboxylase
-mitochondria - oxaloacetate—> PEP
-PEPCK
-cytosol or mitochondria
Why does gluconeogenesis require the malate shuttle?
oxaloacetate is formed in the mitochondria BUT it CANNOT pass the membrane
-oxaloacetate (reduced to) —> malate
-transported to cytosol
-malate (reoxidized)—>oxaloacetate
-gluconeogenesis continues
How does the Cori cycle relate to gluconeogenesis?
The Cori cycle allows lactate produced by anaerobic glycolysis in muscles to be transported to the liver
—> where it is converted back into glucose via gluconeogenesis.
What does reduced mean in biochemistry
Gain electrons
-reduction is part of redox reaction —> one molecule gains electron –> one molecule loses (oxidized)
-often requires H+
Ex: pyruvate reduced to lactate (anaerobic conditions)
Pyruvate + NADH + H+ —>
Lactate + NAD+
-may also include losing O2
ex: ETC when O2 is reduce to form H2O
Reduction examples in biochemisrty
NAD+ —> NADH
-gains 2 electrons and one proton (H+)
Ex: Glycolysis
Glyceraldehyde-3-phosphate+NAD⁺+Pi→
1,3-Bisphosphoglycerate+NADH+H⁺
FAD —> FADH2
-gains 2 electrons and 2 protons (2H+)
Ex: Citric Acid Cycle
CO2 —> Glucose
-photosynthesis
-Calvin Cycle
Oxidation and Reduction Mnemonic
LEO
-Lose Electrons = Oxidation
GER
-Gain Electrons = Reduction
What is the role of Insulin and Glucagon in gluconeogenesis and glycolysis
Insulin = Decreases gluconeogenesis–>
promotes glucose storage/utilization.
Glucagon = Increases gluconeogenesis –> promotes glucose production.
Glucagon is secreted when
Fasting or starvation
Exercise
Low blood glucose levels (hypoglycemia)
= stimulates gluconeogenesis
