Chp 22 - Gluconeogenesis

Exam 4

very important for big picture stuff

what does gluconeogenesis mean in simple terms?

making “new” glucose

gluconeogenesis is the _________ of glucose from _____________ precursors

synthesis, noncarbohydrate

what are the most common precursors in the human body that can be converted to glucose?

pyruvate, lactate, glycerol and amino acids

which two amino acids CANNOT be converted to glucose?

leucine and lysine

what is the major site of gluconeogenesis?

the liver

what site other than the liver can gluconeogenesis occur?

the kidney

when is gluconeogenesis important (in what situation)?

during fasting or starvation

what is glucose the primary fuel for?

the brain

what is glucose the ONLY fuel for?

red blood cells

when a human is fed, its dietary carbohydrates pass through the _______ and are converted into _______

gut, glucose

when a human is fasting or starved, what organ kicks in and begins gluconeogenesis?

the liver

what occurs first: glycogen degradation or gluconeogenesis?

glycogen degradation

why is gluconeogenesis important?

• glucose is the major metabolic fuel in the body

• we need glucose!!! → bad if we run out

glucose is converted to _________ in the cytoplasm of skeletal muscle cells

lactate (lactic acid fermentation)

what are the precursors for gluconeogenesis?

pyruvate, lactate, amino acids, glycerol

lactate is a product of what process…

lactic acid fermentation

lactate is excreted from _____ into the ______ ______

cells, blood stream

lactate can become reabsorbed by the _______ and used as a precursor to produce ________

liver, glucose

where are amino acids derived from?

proteins in the diet or muscle proteins during prolonged starvation

glycerol is a product of…

hydrolysis of triacylglycerols

can animals produce glucose from fatty acids?

NO!!

why can’t animals produce glucose from fatty acids?

• the product of fatty acid degradation is acetyl CoA

• oxaloacetate is only regenerated enough to keep the citric acid cycle going by combining with acetyl CoA to form citrate

• essentially: the processes involved with fatty acid degradation will not produce glucose

plants can produce glucose from fatty acids

true

gluconeogenesis occurs in the _____ while glycolysis occurs in the ______

liver, muscle

refresher: glycolysis converts what to what?

one molecule of glucose to two molecules of pyruvate

explain the processes listed here

breakdown:

GLYCOLYSIS: 1 molecule glucose → 2 molecule pyruvate, 2 ATP

LACTIC ACID FERMENTATION: 1 molecule pyruvate → 1 molecule lactate

all happening in muscle

explain the processes listed here

lactate → pyruvate (oxidation reaction catalyzed by the enzyme lactate dehydrogenase)

pyruvate → glucose GLUCONEOGENESIS

what two organs showcase inter-organ cooperation in a series of reactions?

the muscle and the liver

describe the Cori cycle

• lactate produced by the muscle gets absorbed by the blood stream

• the liver removes the lactate from the blood stream and converts it into glucose

• this glucose can be released into the blood and converted into lactate in the muscle

how many ATP are produced by glycolysis in the muscle?

2 ATP

how many ATP are used by gluconeogenesis in the liver?

6

glycerol is derived from what process?

the hydrolysis of triacylglycerols

glycerol must be converted into what molecule to be processed by gluconeogenesis or glycolysis?

dihydroxyacetone phosphate

the conversion of glycerol to dihydroxyacetone phosphate occurs in how many steps?

two (meaning two enzymes)

what is the intermediate in converting glycerol to dihydroxyacetone phosphate?

glycerol phosphate

what process converts pyruvate into glucose?

gluconeogenesis

is gluconeogenesis the reverse of glycolysis?

NO!!

what is the first step of gluconeogenesis if your precursor is pyruvate?

pyruvate → oxaloacetate

what is the enzyme that catalyzes the first step in gluconeogenesis when pyruvate is the precursor:

pyruvate → oxaloacetate

pyruvate carboxylase

what is the second step in gluconeogenesis if the precursor is pyruvate?

oxaloacetate → phosphoenolpyruvate

oxaloacetate → phosphoenolpyruvate

what is the enzyme?

phosphoenolpyruvate (PEP) carboxykinase

many reactions are common for glycolysis and gluconeogenesis. however, there are three irreversible steps in glycolysis that must be bypassed in gluconeogenesis. list the enzymes for these steps

hexokinase, phosphofructokinase 1, pyruvate kinase

what are the enzymes unique to gluconeogenesis?

pyruvate carboxylase, phosphoenolpyruvate (PEP) carboxykinase, fructose 1,6 biphosphatase, glucose 6-phosphatase

what enzymes in gluconeogenesis are needed to bypass the irreversible step catalyzed by pyruvate kinase in glycolysis?

pyruvate carboxylase and phosphoenolpyruvate carboxykinase

breakdown:

• in glycolysis, pyruvate kinase catalyzes phosphoenolpyruvate → pyruvate

• in gluconeogenesis, 2 enzymes listed above catalyze pyruvate → phosphoenolpyruvate

which enzyme in gluconeogenesis requires a biotin cofactor?

pyruvate carboxylase

(converts pyruvate to oxaloacetate)

where does the conversion of pyruvate to oxaloacetate occur? (gluconeogenesis)

the mitochondria

biotin serves as a carrier of activated ____

CO2

the first step in gluconeogenesis requires what energy source?

first step: pyruvate → oxaloacetate

answer: ATP

the second step in gluconeogenesis requires what energy source?

second step: oxaloacetate → phosphoenolpyruvate

answer: GTP

during the first step of gluconeogenesis for pyruvate, the same _______ is added and immediately removed from the structure in the second step

carbon

think about it, THIS MAKES SENSE bc oxaloacetate has one more CO2 group than pyruvate!!

where is oxaloacetate converted into phosphoenolpyruvate?

the cytoplasm

how does oxaloacetate leave the mitochondria and travel to the cytoplasm?

oxaloacetate gets converted into malate, leaves the mitochondria and gets converted BACK to oxaloacetate once in the cytoplasm

what energy source is used to convert malate to oxaloacetate in the cytoplasm?

NAD+ is used and converted to NADH + H+

once oxaloacetate is in the cytoplasm, what reaction can occur now?

oxaloacetate → phosphoenolpyruvate

enzyme: phosphoenolpyruvate carboxykinase

what is the phosphoryl donor in this reaction:

oxaloacetate → phosphoenolpyruvate

GTP

look at everything outlined here, find what parts are leaving and what parts are being gained (notice the gain of the phosphoryl group)

is this reaction reversible or irreversible in gluconeogenesis?

fructose 1,6-biphosphate → fructose 6-phosphate

irreversible

this reaction is coordinately/oppositely regulated with what enzyme?

fructose 1,6-biphosphate → fructose 6-phosphate

phosphofructokinase-1 (PFK)

fructose 1,6-biphosphate → fructose 6-phosphate

this reaction cleaves phosphate using what molecule?

water

does this step in gluconeogenesis generate ATP?

fructose 1,6-biphosphate → fructose 6-phosphate

NO

where does this reaction occur?

glucose 6-phosphate → glucose

the endoplasmic reticulum

does this reaction generate ATP?

glucose 6-phosphate → glucose

NO

what is the final step in gluconeogenesis?

include reactant, product and enzyme

glucose 6-phosphate → glucose

enzyme: glucose 6-phosphatase

where is glucose 6-phosphate transported before it is catalyzed by glucose 6-phosphatase?

the lumen (interior) of the endoplasmic reticulum

\

what must occur before glucose-6-phosphate can be transported out of the liver?

it must be dephosphorylated

glucose 6-phosphate is dephosphorylated because glucose 6-phosphatase is found (on what organelle?)…

sequestered in the ER lumen

in which organ would you find glucose 6-phosphatase?

the liver

at what times does the liver release glucose into the blood?

during muscular activity and between meals

phosphorylated glucose gets trapped inside the…

cell

what is the net reaction of gluconeogenesis? include all reactants and products (energy sources, molecules, etc)

2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H⁺ + 4 H2O

→

1 glucose + 4 ADP + 2 GDP + 6 P_i + 2 NAD⁺