Gluconeogenesis Lecture – Key Vocabulary

Ten vocabulary flashcards covering enzymes, coenzymes, pathways, and mechanisms essential for understanding gluconeogenesis.

Gluconeogenesis

converts pyruvate and related compounds into glucose; mainly occurs in the liver in mammals

Biotin

enzyme that picks up CO2 and moves it from site 1 to site 2, delivering it to pyruvate in site 2, forming oxaloacetate

Bypass Reactions

The three alternative steps in gluconeogenesis that circumvent the irreversible glycolytic reactions; these include step 1 (glucose + ATP → G6P + ADP), step 3 (F6P + ATP → F1,6BP + ADP), and step 10 (PEP + ADP → pyruvate + ATP)

Glyceroneogenesis

conversion of pyruvate into DHAP via early rxns of gluconeogenesis, followed by a reduction to glycerol 3-phosphate; occurs in adipocytes

First bypass: pyruvate → PEP

pyruvate enters mitochondria from the cytosol; pyruvate carboxylase converts pyruvate into oxaloacetate (using biotin); oxaloacetate converted into malate, transported back to cytosol, then re-converted into oxaloacetate

PEP carboxykinase

converts oxaloacetate to PEP using Mg2+ and GTP; reversible step

second bypass: dephosphorylation

FBPase-1 converts F1,6BP to F6P by hydrolysis of C-1 phosphate

third bypass: hydrolysis

G6Pase catalyzes hydrolysis of G6P into glycose

glycogen

energy storage in the liver; used in glycogen mobilization

fed state

high BG, so glycogen is stored; stimulates insulin release, which binds to liver receptor and promotes glucose uptake and storage, and PP1 release

reciprocal regulation

conditions that favor one pathway inhibit the other

fasted state

low GB; liver releases glucose via glycogen breakdown and gluconeogenesis

PP1

removes P from glycogen synthase and phosphorylase to promote glycogen synthesis and inhibit glycogen breakdown. Also dephosphorylates SPK, inactivating it by preventing it from binding to GPase

glycogen synthase

catalyzes the addition of UDP subunits to growing glycogen molecule; A (dephosphorylated) = active, B = inactive

glycogen phosphorylase

catalyzes the cleavage of glucose subunits; active, phosphorylated = A, inactive, dephosphorylated = B

glucagon

hormone released by the pancreas; binds to GCPR on liver, ultimately activating PKA, which phosphorylates glycogen synthase, deactivating it, and SPK, activating it to activate glycogen phosphorylase

PFK-2

glucagon deactivates, inhibiting glycolysis and promoting neogenesis; insulin activates via PP1, promoting glycolysis and inhibiting neogenesis

F2,6BPase

glucagon activates via PKA, inhibiting glycolysis and promoting neogenesis; insulin deactivates, inhibiting neogenesis and promoting glycolysis

ATP as a regulator

allosteric regulator of PFK-1 and pyruvate kinase (inhibits when [ATP] is high); slows CAC and Acetyl-CoA builds up, so it attaches to pyruvate carboxylate, promoting gluconeogenesis

ADP as a regulator

high levels indicate low energy availability; inhibits pyruvate carboxylase and PEP carboxylkinase

G6P as inhibitor

inhibits hexokinase when in a high energy state, inhibiting glycolysis