• Monosaccharides with five or more carbons
• exist predominantly in a cyclic form in solution
How the body uses glucose
Stored as polysaccharides (glycogen starch) or as sucrose
• Energy Production
• => oxidized via glycolysis to Pyruvate (3C) to give ATP and metabolic intermediates
• => oxidized via the pentose phosphate pathway to give ribose 5phosphate and NADPH
• Used in the synthesis of complex polysaccharides destined for the extracellular matrix and cell
wall. Cellular respiration 20140415
Glucose + oxygen = carbon dioxide + water + ‘energy’
C 6 O12+66O 2à 6CO +26H O +2heat/ATP + FADH2 + NADH + GTP
Steps of cellular respiration
Glycolysis (6carbon) à Pyruvate Oxidation (2x 3carbon) à Citric Acid Cycle (2x 2carbon) à Electron
Transport Chain (electrons (NADH/FADH )) 2
Glycolysis occurs in the cytoplasm
Pyruvate oxidation and citric acid cycle occur in the mitochondria matrix.
Electron transport and chemiosmosis occur in the inner membrane of the mitochondria.
Results in production of 38 ATP per glucose molecule (theoretically), but in reality its lower because of
Substrate level phosphorylation: ATP produced from ADP by a substrate coming from outside of the
electron transport chain.
Oxidative phosphorylation: ATP production from ADP by the electron transport chain
NAD à NADH (gains 1 hydrogen/2 electrons)
1 NAD = 3 ATP after electron transport chain => Major metabolic producer
FAD à FADH (g2ins 2 hydrogens/2 electrons)
1 FADH 2 2 ATP
ADP à ATP (gains phosphate) Glycolysis 20140415
Glucose ▯ Pyruvate Glycolysis 20140415
Oxygen not required (anaerobic)
Glucose ▯ glucose 6 phosphate ▯ fructose 6 phosphate ▯ fructose 1,6 biphosphate ▯ DHP ▯ 2 G3P ▯ 2
Net production of 2 ATP + 2 NADH
Consumes 2 ATP
Produces 4 ATP + 2 NADH
Step 1 ▯ Glucose 6 phosphate production
Conversion of glucose into G6P requires ATP and hexokinase (phosphorylating enzyme).
Hexokinase IsoEnzyme Activity
Isoenzyme = different gene sequence but same activity.
Hexokinases that operate in the muscle don’t have a fine regulation, the goal is to consume glucose.
=> they all have similar kinetics: hyperbolic shape (but they still are under allosteric control) Glycolysis 20140415
=> very high activity at small glucose concentration; K M 0.1 mM (can readily be used for glycolysis)
=> are allosterically inhibited by their product G6P
=> Maintains blood glucose homeostasis; average activity at average glucose concentration; K = ~ M
mM (more regulatory carateristic)
=> regulated by blood glucose level, and F6P not by G6P
Glucose enters the cytosol and gets phosphorylated by hexokinase IV, and becomes G6P and then is
converted to F6P.
Glucose positively regulates hexokinase IV by binding to a regulatory protein that makes hexokinase IV
leave the nucleus and come in the cytosol.
Fructose 6 phosphate negatively regulates hexokinase IV by binding to a regulatory protein that will move
hexokinase IV out of the cytosol (bring it back to the nucleus). Glycolysis 20140415
High glucose in the liver cell => production of G6P ▯ F6P => if unused (rest, very big meal, eating while not
being hungry) => F6P accumulates => inhibit glycolysis
High glucose in the liver => production of G6P ▯ F6P => if used (exercise, small meal, very hungry) => F6P
doesn’t accumulate => doesn’t inhibit glycolysis
Step 2 ▯ Fructose 6 phosphate production
Doesn’t require any enzyme or energy.
Only a change structure.
Step 3 ▯ Fructose 1,6 biphosphate production
The conversion of F6P to F1,6BP requires ATP and PFK1 (phosphorylating enzyme)
This production (specifically the enzyme PFK1) is upregulated by :
fructose 2,6 biphosphate (see below)
ADP (reflects a need for energy)
And is downregulated by:
ATP (reflects high glucose level)
Citrate (reflects low activity of the citric acid cycle, low need of glucose)
Regulation of fructose 2,6 biphosphate
Is made from fructose 6 phosphate using energy and PFK2 (phosphorylating enzyme) Glycolysis 20140415
in blood glucose level leads to in blood insulin level
=> Insulin increases PFK2 activity (by dephosphorylating it) thus increasing F26BP levels
Result: glycolysis in the liver
=> Blood glucose levels are reduced Gluconeogenesis 20140415
In mammals metabolic precursors for gluconeogenesis include :
glucogenic amino acids
Is the opposite of glycolysis and so they can’t occur at the same time.
Those two reactions are independently inversely regulated at three distinct points by separate enzymes.
• Conversion of fructose 1,6 biphosphate in fructose 6 phosphate
Requires H2O and fructose 1,6 biphosphatase (dephosphorylating enzyme).
FBPase1 activity is downregulated by:
fructose 2,6 biphosphate (see below) Gluconeogenesis 20140415
Regulation of fructose 2,6 biphosphate
F26BP is the key allosteric regulator for PFK1 and FBPase1: it upregulates glycolysis and down regulate
gluconeogenesis at the same time.
Is made from fructose 6 phosphate usi