Carbohydrate metabolism
CHO supply• Diet• Endogenous reserves
– Liver– Muscle– Blood
• Limited
• Anaerobic glycolysis– Anaerobic
• Does not need oxygen • Occurs in the cytoplasm• Glucose degradated to:
– 2 pyruvate– Then pyruvate converted to lactate
Anaerobic glycolysis
Anaerobic Glycolysis
• Pathway is the same regardless of end-product– Lactate is the end product of
anaerobic glycolysis– Pyruvate is the end-product
of aerobic glycolysis• Pyruvate then converted to
– Acetyl-CoA– Enters Kreb’s cycle
Anaerobic glycolysis
• Step 1– Glucose uptake from blood
• Rate limiting step #1• GLUT 4
– Transporter than facilitates passage of glucose into the cell
• Glucose then phosphorylated• Energy added
– Hexokinase– Irreversible
– If Glycogen is the start point
• Broken down to glucose-1-P– Phosphorylase– Activated by epinephrine,
Calcium– Requires ATP
•Step 2•Conversion of G-6-P to F-6-P
•Phosphoglucose isomerase
•Step 3 (energy added)•Phosphorylation
•F-6-P to F 1,6-biphosphate
•Phosphofructokinase•Rate limiting step #2
Anaerobic glycolysis
Anaerobic glycolysis• Step 4
– Splitting of one molecule into 2
• Aldolase• G-3-P and DAP
– Interconvertable– G-3-P is what proceeds
• Step 5– G-3-P to 1,3 BPG– Pi comes from within the
cell– First payoff step
• NADH + H+
• Step 6– ATP formation 1– Phosphoglycerate kinase
• 3-phosphoglycerate formed
Anaerobic glycolysis
• Step 7– Phosphoglycerate mutase
• 3PG to 2-phosphoglycerate
• Step 8– Enolase
• 2PG to Phosphoenolpyruvate (PEP)
• Step 9– Second energy formation
step (ATP)– PEP to pyruvate– Pyruvate kinase
Anaerobic glycolysis
• Step 10– Conversion of Pyruvate to
Lactate– Oxidation of NAD+
• Recycles NAD+ for Step 5• NAD+ is a co-factor in the G-3P
dehydrogenase Rx• This allows glycolysis to
continue at a fast rate
• Net ATP from one cycle of anaerobic glycolysis– 2ATP needed (Steps 1 and
3)– 4 ATP produced
• 2 each at steps 6 and 9
– 2 Net ATP
• Thus, anaerobic glycolysis– Inefficient– Fast
Aerobic Glycolysis• Glucose to pyruvate
– NET• 2 ATP• 2 NADH + H+
– These are shuttled into the mitochondria by the GP shuttle system» 2 ATP
• Pyruvate converted to acetyl-CoA– Pyruvate dehydrogenase
complex– Enters Kreb’s cycle– 15 ATP
– Total• 2 ATP directly• 4 ATP from NADH• 30 ATP from pyruvate
Regulation of glycolysis
• Regulated at various points in the cycle– Glycogen breakdown
• Glycogen phosphorylase
– Glucose entry into the cell• Hexokinase
– Phosphofructokinase• 3rd Step, requires ATP
– Pyruvate dehydrogenase Rx
• Conversion of pyruvate to Acetyl-CoA
1
3
2
4Acetyl-CoA
Glycogen phosphorylase• Regulation is complex• Two forms
– Phosphorylase a (active)– Phosphorylase b (inactive)
• Activation (Step 1)– Epinephrine– Ca++
• This allows rapid breakdown of glycogen only during activity
• Step 2– Activates adenylate cyclase
• Converts ATP to cAMP– Intercellular messenger– Activates protein kinase
Glycogen phosphorylase• Step 3
– Activation of phosphorylase kinase
• ATP required
• Step 4– Activation of Phosphorylase a
• ATP required
• Deactivation– Generally, a reverse of above
• Ca++ levels fall• Epinephrine levels fall• cAMP levels fall
Hexokinase• Reaction wherein glucose
is taken up from the blood and phosphorylated– Requires GLUT-4 transporter
• Facilitates diffusion of glucose into cell
• Activated by insulin AND exercise
– ATP• Activated by
– Contractions– Pi
• Inhibited by – G-6-P
GLUT-4
Phosphofructokinase• First energy requiring
step of glycolysis– ATP– “rate-limiting” enzyme– Inhibited by
• High ATP and PCr levels
• Citrate (1st product of Kreb’s cycle)
– Activated by• Elevated ADP, AMP, Pi,
ammonia
Possible connection between fat and CHO metabolism
• When fatty acid metabolism is accelerated– Long-term exercise
• Acetyl-Coa builds up– Fatty acids are essentially broken down
to acetyl-CoA
• This causes an increase in Citrate, which inhibits glycolysis
– Important, as it conserves glucose at a time when it is starting to run out
Gluconeogenesis
• Prolonged exercise >2hrs– Deplete muscle and
liver glycogen
• In the absence of dietary CHO– Liver can use non-CHO
sources to help maintain blood glucose levels
– Gluconeogenesis• Lactate• Glycerol• Some amino acids
Gluconeogenesis• Takes place mostly in the
liver– Kidney (much less)– Skeletal muscle?
• Glycogen but not glucose
• Gluconeogenesis– Essentially “reverse” glycolysis– Couple of slightly different
steps
Gluconeogenesis• Conversion of pyruvate to
PEP (phosphoenolpyruvate)– Pyruvate kinase Rx is
irreversible– Pyruvate carboxylase and
PEP carboxykinase• Pyruvate carboxylase
– Pyruvate to Oxaloacetate» ATP
• PEP carboxykinase– Oxaloacetate to PEP
» GTP
– PFK step is also irreversible• Fructose 1,6 biphosphatase
– Hexokinase step is irreversible
• Glucose-6-phosphatase
Gluconeogenesis• Skeletal muscle
– No glucose-6-phosphatase
• Can convert G6P to G1P– Phosphoglucomutase
• G1P converted to UDP-glucose– Glucose 1-phosphate
uridyltransferase
• Glucose residue is attached glycogen primer– Formed as a part of this Rx– UDP is recycled