Glycolysis for WSU Biochem Test 4

a central sequence of reactions in biochemistry that converts glucose into two molecules of pyruvate.

It is taken into the mitochondria and burned to produce CO2 and several NADH and FADH2.

Dihydroxy Acetone

Glyceraldehyde

Glycerate

Pyruvate

Phosphoryl transfer

Phosphoryl shift

isomerization of a ketose into and isomer aldose or vise versa

adds a carbon in the form of CO2 to a molecule (Usually requires a biotin coenzyme)

aldol cleavage (splits a C6 into two C3, one is always and aldose and the other a ketose)

Oxidize alcohols and other molecules (FAD+ and NAD+ coenzymes)

• Glucose + ATP ---> G6P + ADP + H+ via hexokinase.
• A Phosphoryl transfer.
• Equilibrium is skewed to the right by coupling with ATP hydrolysis.

• Hexokinase requires ATP and Mg2+ or Mn2+.
• Mg or Mn complex with negative charges on ATP phosphates

• G6P <-----> F6P via phosphoglucoisomerase.
• Isomerization (general acid/base) aldose to ketose.
• Mass action

• F6P + ATP ---> F-1,6BP via phosphofructokinase.
• A phosphoryl transfer.
• Allosterically controlled

• Taught form = lower affinity for F6P, promoted by high levels of ATP (prevents too much lactic acid)
• Relaxed form = higher affinity, promoted by high levels of ADP.
• Inhibited by citrate.

• F-1,6BP <---> DHAP + G3P via aldolase.
• Reverse of an aldol condensation.
• Controlled by mass action

• G3P from carbons 4,5,6.
• DHAP from 1,2,3.

• DHAP <---> G3P via Triosephosphate isomerase.
• Isomerization (ketose to aldose) reaction.
• Mass action, G3P is pulled away for metabolic processes.

• G3P + NAD+ + Pi <---> 1,3BPG + NADH via G3P dehydrogenase.
• Oxidation.
• Substrate level phosphorylation.

Unfavorable Phosphorylation is coupled with favorable oxidation (no ATP required)

• The rxn is unfavorable under standard conditions. Synthesis of 1,3BPG is coupled with favorable oxidation of the aldehyde to an acid.
• Aldehyde + NAD + H2O ---> acid + NADH + 2H + +

• 1,3BPG + ADP <---> 3PG + ATP via phosphoglycerate kinase.
• Reverse of a kinase reaction.
• High energy transfer potential of the phosphoanhydride bond found in 1,3BPG favors or couples the unfavorable synthesis of ATP

• 1,3 BPG + ADP <---> 3PG + ATP.
• 2mol ATP and 2 NADH/glucose

• Arsenate (a poison) is very similar to phosphate and can act as the nucleophile in place of inorganic phosphate (Pi) which uncouples the formation of ATP in reactions 6 and 7.
• Phosphate and arsenate are chemically similar. However the arsenate bond is water labile and is easily hydrolyzed in the presence of water without an enzyme.
• The placement of arsenate onto G3P as it is converted to 1,3PG � Arsenate uncouples the synthesis of an ATP

• 3PG <---> 2 PG via phosphoglycerate mutase.
• Phosphoryl transfer reaction - high energy molecule constructed from low energy bond by removing -OH group.
• Mass action.

• 2PG <---> PEP via enolase.
• Formation of a double bond via elimination rxn.
• Phosphorylation.

PEP

• PEP + ADP ----> pyruvate + ATP via pyruvate kinase.
• Reverse of a kinase rxn.
• Allosterically regulated

2 atp and 2 NADH/mole glucose

The enzyme is basically regulated by phosphorylation through a signal initiated by the peptide hormones, glucagon and insulin.

• When blood sugar levels are high insulin is released from the pancrease and signals the fed state. Insulin initiates a series of events which cause the cells to take in additional glucose
• as part of this process P-PK (phosphorylated PK) is dephosphorylated and the enzyme changes to an open active conformation (higher binding affinity) ----> PK

• When blood sugar levels are low, glucagon is released from the pancrease and signals the fasting state. In this state sugar is reserved for the brain and muscle.
• The signal sent by glucagon activates a kinase which phosphorylates PK to P-PK conformation. The P-PK conformation is a taught conformation with low binding affinity for PEP.
• Net result � the glycolytic path is slowed way down in liver and other fuels are used to actually drive the synthesis of glucose and release it into the blood stream

It is converted to lactic acid

Buy time for survival - NADH produced in glycolysis is sacrificed to produce as much ATP as possible with limiting O2.

Pyruvate + NADH <---> Lactate + NAD+ via lactate dehydrogenase

NADH is sacrificed so that production of ATP can continue when O2 is limiting

• Pyruvate <---> Acetaldehyde + CO2 via pyruvate decarboxylase
• Acetaldehyde +NADH ---> Ethanol + NAD+ via alcohol dehydrogenase

It converts them into useful materials.

• It is almost completely filtered by the liver and processed before release into the blood stream.
• If not needed for energy, F6P is converted into glucose for storage or release into the blood stream.

• Fructose + ATP ----> F1P + ADP via fructokinase.
• F1P is then split by alsolase into DHA and Glyceraldehyde.
• DHA is phosphorylated into DHAP and converted to G3P.
• Glyceraldehyde + ATP ---> G3P + ADP via glyceraldehyde kinase.

• Galactose + ATP ---> Gal-1P + ADP.
• UDP-Glucose + Gal-1P <---> UDP-Galactose + Glu-1P via Gal-1p Uridyl transferase.
• UDP-Gal <---> UDP-Glu via UDP galactose epimerase.
• UDP-Glu is recycled to part 3 and the cycle continues until Gal levels drop.
• Glu-1P is then converted to Glu-6P and sent through glycolysis.

Problems with the uridyl transferase.

2

They are epimers