Gluconeogenesis

What happens in the first step of gluconeogenesis?

The first step, pyruvate carboxylase converts pyruvate to oxaloacetate

• carboxylation using a biotin cofactor

• requires transport into the mitochondria

What happens in the second step of gluconeogenesis?

The second step, phosphoenolpyruvate carboxykinase converts oxaloacetate to PEP.

• phosphorylation from GTP and decarboxylation

• occurs in mitochondria or cytosol depending on the organism

How does biotin function in pyruvate carboxylase (site 1, site 2, and lysine)?

Biotin is covalently attached to a Lys residue and acts as a swinging CO₂ carrier between two active sites. It picks up CO₂ at site 1 and drops it off at site 2

There are two different pathways that can create PEP, how are these pathways regulated?

These reactions depend on the conc. of NADH

There are two pathways that can make PEP explain the one where PEP gets shipped out of the mitochondria.

In the cytosol lactate in reduced to pyruvate, which then pyruvate gets shipped into the mitochondria. Then that pyruvate is changed into oxaloacetate which is then turned into PEP. This PEP is then shipped out of the mitochondria

There are two pathways that can make PEP explain the one where Malate gets shipped out of the mitochondria.

First in the cytosol pyruvate gets shipped into the mitochondria. Then pyruvate gets changes into oxaloacetate which then gets changed into malate. Malate then gets shipped out of the mitochondria. After being shipped out it gets turned into oxaloacetate. Then oxaloacetate gets turned into PEP

The inner mitochondrial membrane is selectively permeable, what is permeable here? What cannot escape here?

Malate, PEP, and pyruvate are permeable, while oxaloacetate cannot escape

Oxaloacetate can be utilized in what cycle is needed?

The citric acid cycle (Kreb’s cycle)

Oxaloacetate can be converted to what to allow transport to cytosol for gluconeogenesis?

Oxaloacetate can be converted to PEP or malate to allow transport to cytosol for gluconeogenesis.

In the step in gluconeogenesis what happens in fructose 1,6-bisphosphate → fructose 6-phosphate?

• this changes happens by fructose bisphophatase-1

• coordinately/oppositely regulated with PFK

• cleaves phosphate with water

• DOES NOT generate ATP

In the step in gluconeogenesis what happen when glucose 6-phosphate → glucose?

• this change happens by glucose 6-phosphatase

• segregated in the endoplasmic reticulum

• cleaves phosphate with water

• DOES NOT generate ATP

Gluconeogenesis is expansive, why does the body do through it when it has to use so many resources?

it is physiologically necessary: brain, nervous system, and red blood cells generate ATP ONLY from glucose

Gluconeogenesis allows for the generation of glucose when glycogen stores are depleted when is that?

• during starvation

• during vigorous exercise

• can generate glucose from amino acids, BUT NOT FATTY ACIDS

Animals can produce glucose from sugars or proteins what are those sugars and proteins?

• sugars: pyruvate, lactate, or oxaloacetate

• protein: from amino acids that can be converted to citric acid cycle intermediates

Why can animals not produce glucose from fatty acids?

• the product of fatty acid degradation is acetyl-CoA

• cannot have a net conversion of acetyl-CoA to oxaloacetate