Biochemistry: Gluconeogenesis

Front 1

What is gluconeogenesis?

Back 1

Synthesis of glucose from amino acids, lactate, and glycerol

Front 2

What is meant by non-glucose precursors?

Back 2

Means you're using molecules that weren't derived from glucose or glucose-based molecules (such as glycogen)

Front 3

What are the three enzymes that go in the reverse direction as the three irreversible steps in glycolysis?

Back 3

Glucose-6-phosphatase [Hexokinase]
Fructose 1,6-bisphosphatase [PFK]
Pyruvate carboxylase (uses ATP pyruvate-->OAA) AND PEP carboxykinase (uses GTP OAA-->PEP) [to counter pyruvate kinase]

Front 4

How many high energy bonds per glucose synthesized?

Back 4

6 - 2 ATP from pyruvate --> OAA, 2GTP from OAA --> PEP, 2 from 3PG -->1,3BPG

Front 5

Which enzyme bypasess the hexokinase reaction? Is it found in skeletal muscle?

Back 5

Glucose-6-phosphatase
Found in liver and kidney

Front 6

Which enzyme bypasess PFK?

Back 6

Fructose 1,6 bisphosphatase

Front 7

What does reciprocal regulation mean?

Back 7

Something that would stimulate glycolysis would at the same time inhibit gluconeogenesis and vice versa to avoid futile cycles.

Front 8

How is F2,6BP made?

Back 8

From F6P, by PFK2.

Front 9

What effect does insulin have on the production of F2,6BP?

Back 9

Insulin dephosphorylates PFK2, which makes it produce F2,6BP, which stimulates PFK, pushing glucose through the glycolytic pathway.

Front 10

What effect does glucagon have on the production of F2,6BP?

Back 10

Glucagon phosphorylates PFK2, which makes it convert F2,6BP into F6P, which means that it is no longer stimulating PFK activity.

Front 11

What stimulates F1,6bisphosphatase? What inhibits it?

Back 11

ATP and citrate (same stuff that inhibits PFK!)

F2,6BP is a competitive inhibitor.

Front 12

How is pyruvate converted back into PEP?

Back 12

Pyruvate carboxylase uses ATP and biotin to convert pyruvate to OAA (in mitochondria)

PEP carboxykinase uses GTP to convert OAA to PEP. Also takes off a CO2. (mito and cytoplasm)

Front 13

How is pyruvate carboxylase regulated?

Back 13

Allosterically activated by acetylCoA
Competitively inhibited by ADP

Front 14

Which gluconeogenic step requires NADH?

Back 14

1,3 bisphosphoglycerate --> glyceraldehyde 3 phosphate

Front 15

What are the sources of carbon skeletons for gluconeogenesis?

Back 15

Lactate -->pyruvate (LDH)
Amino acids
Glycerol --> triose phosphates (glycerol kinase)

Front 16

Which amino acids can form glucose?

Back 16

tryptophan --> alanine --> pyruvate
Aspartate --> OAA
Glutamine, arginine, ornithine, proline, histidine --> glutamate --> a-ketoglutarate
Cysteine --> pyruvate
Valine --> succinylCoA
Leucine, isoleucine --> acetylCoA
Phenylalanine, tyrosine --> fumarate
Serine --> pyruvate
Glycine --> --> OAA
Threonine -->succinylCoA, pyruvate, glycine

Front 17

How does the body metabolize free glycerol produced during fat metabolism?

Back 17

Only in the liver because it has glycerol kinase. Free glycerol from adipose tissue will get picked up in the liver and get converted by glycerol kinase to glycerol3PO4 which then gets converted to DHAP (makes NADH) which then gets converted to glyceraldehyde3PO4

Front 18

What is the alanine cycle and what does it do?

Back 18

Muscles can break down branched chain amino acids (BCAAs) but the liver can't. The muscles use pyruvate and BCAAs to generate alanine and branched chain keto acids (BCKAs). BCKAs can be used in the TCA cycle for energy, and alanine is sent to the liver, where it gets converted to pyruvate. The NH3 is sent to urea. The liver can then send back the newly processed glucose back to muscle.
End result: No net gain or loss of glucose, NH3 gets sent to urea cycle.

Front 19

What tissue is the only one that can utilize glycerol for gluconeogenesis?

Back 19

Glycerol kinase is only found in the liver. It uses ATP to turn glycerol into glycerol 3 phosphate, which then uses NAD and glycerol phosphate dehydrogenase to make DHAP. DHAP <--> Glyceraldehyde 3 phosphate <--> F1,6BP --> --> Glucose.