lecture 11 gluconeogenesis

Question 1

what is gluconeogenesis?

Answer 1

creates new glucose molecules using noncarbohydrate precursors such as lactate, pyruvate, and some amino acids which can be converted into pyruvate

Question 2

which organ is primarily responsible for creating new glucose?

Answer 2

liver

Question 3

what’s the cori cycle?

Answer 3

Lactate as a precursor can come from the working muscle to the liver via the blood and liver returns glucose via the blood

Question 4

what is glucose synthesized from?

Answer 4

pyruvate. Noncarbohydrate precursors of glucose are first converted into pyruvate or enter the pathway at later intermediates

Question 5

Most of the decrease in free energy in glycoly- sis takes place in the three essentially irreversible steps catalyzed by ___

Answer 5

hexokinase, phosphofructokinase, and pyruvate kinase.

Question 6

what happens to the 3 irreversible (large negative delta G) steps in glycolysis during gluconeogenesis?

Answer 6

these steps must be bipassed

Question 7

1st step of gluconeogenesis- how do you create PEP?

Answer 7

Carboxylation of pyruvate in the mito matrix to form oxaloacetate

Question 8

step 2 gluconeogenesis; what happens with oxaloacetate?

Answer 8

(OA -> PEP : remove COO-, phosphorylate. Large negative delta G) OA is decarboxylated. This step has enough free energy to allow a phosphate group to attach to the 3-carbon fragment, forming PEP.

Question 9

after you create PEP what happens?

Answer 9

all steps are simply reversed until you reach Fructose, 1,6 bisphosphate

Question 10

what happens once you reach fructose 1,6 bisphosphate?

Answer 10

Fruc 1,6 BP – remove PO3 group. Turns into fruc 6 phosphate

Question 11

fruc 6 phosphate –> glucose?

Answer 11

convert fruc 6 phosphate into a glucose via ‘isomerase’ ; now its glucose-6-phosphate (theres a phosphate at the 6 position of a regular glucose molecule) glucose-6-phosphatase removes one phosphate from G6P to create glucose (hexokinase cannot be reversed)

Question 12

The formation of oxaloacetate by pyruvate carboxylase occurs in the ____

Answer 12

mitochondria

Question 13

how is oxaloacetate shipped into the cytoplasm if there is no transporter for it?

Answer 13

reduced to malate, shipped out, and then reoxidized to oxaloacetate with the generation of cytoplasmic NADH

Question 14

why do we want oxaloacetate in the cytoplasm?

Answer 14

all glycolytic enzymes are located in the cytoplasm

Question 15

The generation of free glucose occurs only in the ___because no other cell type has the phosphatase enzyme.

Answer 15

liver

Question 16

what turns glucose-6-phosphate into glucose to finish gluconeogenesis?

Answer 16

glucose-6-phosphatase- removes the phosphate group to make it normal free glucose

Question 17

where does glucose-6-phosphatase live?

Answer 17

in the ER on the lumen side

Question 18

based on glucose-6-phosphatase’s location, how do you finish gluconeogenesis to create free glucose?

Answer 18

Glucose 6-phosphate must be transported into the lumen of the endoplasmic reticulum for the reaction to take place. Then, glucose is shipped back to cytoplasm and by facilitated transport sent back to blood

Question 19

how many ATP equivalents are used in gluconeogenesis

Answer 19

6

Question 20

overall gluconeogensis reaction

Answer 20

Question 21

___high transfer potential phosphoryl groups are spent in synthesizing glucose from pyruvate

Answer 21

six

Question 22

how is gluconeogenesis regulated?

Answer 22

If energy charge is low, glycolysis predominates. If glucose is low, gluconeogenesis is active.

Question 23

do glycolysis and GNG occur at the same time?

Answer 23

no, its one or the other, and it depends on current levels in the cell; Glycolysis will predominate when glucose is abundant, and gluconeogenesis will be highly active when glucose is scarce.

Question 24

what are the 3 points in glycolysis/GNG where they are regulated to determine which path will proceed?

Answer 24

surprise surprise, the 3 irreverisble steps! you’d need to stop those 3 enzymes from working in either case- either to prevent glycolysis or prevent GNG

Question 25

energy charge of cell; ATP-generating (catabolic) pathways are inhibited by a ___ (high/low) energy charge

AMP is the signal for ___ (high/low) energy state

Answer 25

high

high charge, lots of ATP, tells cell ‘stop making atp’

2. low

Question 26

Substrates for gluconeogenesis come from ___, ___ or ___ that can be converted into glycolytic intermediates.

Answer 26

pyruvate, amino acids or lactate

Question 27

___ produced by muscle during contraction is released into the blood. Liver removes the lactate and converts it into glucose, which can be released into the blood

Answer 27

lactate

Question 28

who puts CO2 onto pyruvate to form oxaloacetate( hint its a vitamin)

Answer 28

biotin

Question 29

how do we go from pyruvate -> PEP since we can’t use pyruvate kinase?

Answer 29

form oxaloacetate as an intermediate. add COO- then decarboxylate it in an energy rich reaction to form PEP. GTP-> GDP to add energy

Question 30

why is oxaloacetate shipped into cytoplasm

Answer 30

carboxylation of pyruvate only occurs in matrix, however, all necessary enzymes are in cytoplasm. solution: ship OA to the cytoplasm. but no transporter for it in mito membrane- however, there is a transporter for malate, so we bring it out as malate and then reconvert it to OA, to then decarboxylate it to PEP

Question 31

what’s special about the last step of gluconeogensis (G6phosphatase to gluose)?

Answer 31

highly regulated, only gets dephosphorylated in times of need for glucose

enzyme is hiding in ER lumen. only in kidney/liver. doesnt automatically remove phosphate from glucose so that we can control G6P buildup

Question 32

pyruvate carboxylase

Answer 32

first step of GNG. turns pyruvate into OA