lumen of intestines

kidney

• symport with sodium
  • sodium goes down transport gradient
  • glucose just goes with it
  • gradient maintianed by Na/K pump (2 K in with 3 Na out)

muscle

adipose

• vesicles in cytosol contain GLUT4
• these vesicles with transporters moved into membrane by a signal from insulin
• if muscle: exercise can trigger movement of transporter to membrane

• glucose phosphorylated to G6P via hexokinase
• purpose
  • keeps glucose concentration in the cell low
  • it traps glucose in the cell

• I- brain
• II
• III
• IV (glucokinase- can't phosphorylate other hexoses due to the Km of these sugars not being in physiological range)- liver

• low Km's for glucose (10^-4 mM range)
  • at low glucose concentration, they are active
• are product inhibited
• will phosphorylate other hexoses

• high Km for glucose (10 to 15 mM)
• not product inhibited
• Km's for other hexoses are not in physiological range

Why its called glucokinase

• via glucose 6 phosphatase
• found in ER of liver, intestines, kidney

So in muscle, once we get to G6P, there is no way to get it out.

2 NADH's

2 ATP's

2 pyruvates

• preparation of glucose for splitting
• splitting
• oxidation portion

• glucose → G6P
• via hexokinase
• hydrolyze ATP to ADP/P

• G6P → F6P
• via hexo-isomerase

• F6P to F16P
• via PFK1
• hydrolyze ATP to ADP/P

Reaction is irreversible and committed step

• F16P to DHAP and G3P
• via aldolase

• DHAP → G3P
• via triose isomerase

This is freely reversible

• G3P to 1,3 BPG
• via G3P dehydrogenase
• 2 NAD reduced to 2 NADH

• 1,3 BPG to 3PGA
• via 3 PGA kinase
• produce 2 ATP's

Unlike most kinases, this is freely reversible

• 3 PGA to 2 PGA
• via 3 PGA mutase

• 2PGA to PEP
• via enolase
• removes water from compound

Very negative Gibb's free energy

• PEP to pyruvate
• via pyruvate kinase
• produce 2 ATP

Irreversible

• irreversible steps
  • PFK 1
  • PK
• both are allosteric sites (multiple subunits)
• ATP is negative modulator for both enzymes
• NADH/NAD ratio in cytosol controls activity of G3PDH

malate shuttle (requires Asp, Glu) (mainly in liver)

alpha glycerol phosphate shuttle (mainly in muscle)

1. convert DHAP to alpha glycerol phosphate via oxidation of NADH to NAD
   1. via alpha glycerol phosphate DH
2. alpha glycerol phosphate crosses outer mitochondrial membrane and is in intermembrane space
3. flavoprotein within inner mitochondrial membrane is reduced to FADH2, leading to oxidation of alpha glycerol phosphate to DHAP via flavin dependent alpha glycerol phosphate dehydrogenase
4. DHAP can leave out out the outer mitochondrial membrane to cytosol

• coupled to formation of lactate from pyruvate
• pyruvate converted to lactate via lactate dehydrogenase
• coupled to oxidation of NADH to NAD
  • this NAD can feedback into glycolysis, allowing glycolysis to continue

• produce two lactates and 2 ATP's (no NADH's)
• glycolytic pathway must run faster

liver

1. fructose to F1P via fructokinase
2. F1P to DHAP and glyceraldehyde via F1P aldolase
3. glyceraldehyde  converted to G3P via triose kinase

It can feed into glycolysis.

• fructosemia (fairly benign)
• fructouria
• develop dislike for sugar (limit uptake of sugar)

• enlarged liver
  • build up of fructose 1 phosphate (we are tying up phosphate groups)
  • impairs metabolism

1. galactose to gal-1P via galactokinase via ATP hydrolysis to ADP/P
2. gal-1P combines with UDP-glucose to create G1P and UDP-galactose via gal-1P uridyl transferase
   1. regenerate UDP-glucose from UDP-galactose via UDP-galactose-4'epimerase
3. G1P to G6P via glucomutase

Feeds into glycolysis

• galactosemia
• galactouria
• opaqueness in eye
  • forming cataracts due to increase galactose
  • turn it into an alcohol (they have no way to get out of the cell)
  • pull water in, disrupts structure of crystalline

• possible forming cataracts
• liver damage (tying up phosphate groups)
• Galactosemia, galactouria
• build up of Gal-1P