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Gluconeogenesis Cheat Sheet (DRAFT) by

This is a draft cheat sheet. It is a work in progress and is not finished yet.

Definition

the denovo synthesis of glucose, requires both mitoch­ondrial and cytosolic enzymes
Substr­ates: Glycerol, Lactate, amino acids
4 unique reactions in glucon­eog­enesis to overcome irreve­rsible reactions in glycolysis
Glucon­eog­enesis is regulated by glucagon, substrate availa­bility, acetyl-CoA and AMP

Substrates

Glycerol
released during TAG hydrol­ysis, converted to G3P by Glycerol kinase, then to DHAP by G3P DH, DHAP can then enter glucon­eog­enesis
Lactate
released by excreting skeletal muscles and nonmit­och­ond­riated cells, used via cori cycle where lactate is oxidized to pyruvate
Amino Acids
hydrolysis of tissue proteins lead to production of α-KG, which can then form OAA via the TCA cycle. Gives rise to ketone bodies.

Regulation

Glucagon (stimu­lant)
changes allosteric effectors (lower hepatic F2,6BP), covalent modifi­cation of enzyme activity (GPCR, cAMP, CDK-A; diverts PEP to glucon­eog­ene­sis), increase PEPCK transc­rip­tion.
Substrate availa­bility
more substrate = increased rate, decreased insulin leads to mobili­zation of AA to provide carbon skeletons, ATP and NADH is provided by FA[O]
Acetyl-CoA (allos.)
increases TAG hydrolysis in adipose, increasing FA above β-[O], Acetly-CoA accumu­lates and activates PC. Diverts pyruvate toward glucon­eog­enesis.
AMP inhibition (allos.)
F1,6BP inhibited, reciprocal reguation of glycolysis and glucon­eog­enesis
 

Reactions

Pyruvate Carbox­ylase
Pyruvate carbox­ylated to OAA, then to PEP by carbox­yki­nase. PC require biotin as a coenzyme. PC has two functions: produce PEP and replenish OAA in the TCA cycle. PC is allost­eri­cally activated by Acetyl­-CoA.
Reducation of OAA to malate
OAA can't transfer through mito membrane, so must be reduced to malate first by Malate DH. Once on the other side, MDH will reoxidize it to OAA. NADH is used throughout this process.
PEP carbox­ykinase
OAA converted to PEP, this is performed by coupling of PC to PEPCK. PEP can then continue through reverse glycolysis reactions until F1,6BP.
F1,6BPase
Key regulatory step, inhibited by high AMP:ATP ratio and by F2,6BP.
G6P DP
G6P DP hydrolyses G6P, bypassing glucok­inase. Primarily takes place in the liver, requires G6P transl­ocase to transport G6P through ER membrane.