Carbohydrates in Glycolysis

Dietary Carbohydrate Entry into Glycolysis

• Dietary glycogen and starch breakdown products can be converted into glycolytic intermediates to enter the glycolytic pathway
• Endogenous glycogen is catabolized into glucose 1-phosphate by phosphorylase
• Glucose, fructose, and other monosaccharides can enter the glycolytic pathway after conversions

Fates of Carbohydrates in Glycolysis

• Glycogen and starch are cleaved into glucose molecules by glycogen phosphorylase
• Glucose 1-phosphate is created which is then converted into glucose 6-phosphate by phosphoglucomutase
• Inorganic phosphate is used as the phosphate source by Glycogen phosphorylase
• Some energy of the glycosidic bond is preserved due to phosphorolysis rather than hydrolysis.
• Disaccharides go through hydrolysis
• Lactose hydrolyzes to glucose and galactose
• Sucrose hydrolyzes to glucose and fructose
• Fructose, galactose, and mannose enter glycolysis at different points

Intracellular Glycogen Catabolism and Phosphorolysis

• Glycogen phosphorylase catalyzes the reaction where inorganic phosphate attacks the nonreducing end of glycogen
• (α1→4) glycosidic linkage joins the last two glucose residues at the nonreducing end of the glycogen molecule, which is attacked by phosphate
• This reaction produces glucose 1-phosphate and shortens the glycogen polymer by one glucose unit
• Glycogen phosphorylase catalyzes phosphorolysis instead of hydrolysis
• Phosphorolysis preserves some of the glycosidic bond's energy within the phosphate ester that is formed

Glycolysis's Net ATP Yield

• The preparatory phase does not require glucose phosphorylation by hexokinase
• The investment phase consumes 2 moles of ATP per mole of glucose; the payoff phase yields 4 moles, resulting in a net yield of 2 ATP
• When glucose is derived from glycogen, investment phase requires only one ATP, so the result is a net yield of three ATP

Fates of Pyruvate Under Anaerobic Conditions

• Under aerobic conditions, pyruvate is oxidized to acetate as acetyl-CoA and the NADH from Ga 3-P dehydrogenation is reoxidized to NAD+ by the transfer of electrons to O₂ in mitochondrial respiration
• Under hypoxic conditions, NADH from glycolysis cannot be reoxidized by O₂
• NAD⁺ regeneration failure deprives the cell of an electron acceptor for Ga 3-P oxidation, stopping energy-yielding reactions in glycolysis
• Pyruvate is converted to two acetyl-CoA molecules, which then enter the TCA cycle, followed by producing ATP, carbon dioxide, and water through oxidative phosphorylation under aerobic conditions.
• Pyruvate in yeast is used to produce ethanol and carbon dioxide through fermentation

Lactate Formation

• Under anaerobic conditions in humans, pyruvate is fermented to form lactate
• Reduction of pyruvate to lactate occurs under hypoxic or anaerobic conditions to regenerate NAD⁺, which occurs in contracting skeletal muscle and erythrocytes
• NADH is oxidized to regenerate NAD⁺ by lactate dehydrogenase which reduces pyruvate to lactate under anaerobic conditions
• Cells with mitochondria oxidize NADH to NAD+ in oxidative phosphorylation, so pyruvate is further metabolized as lactate is not formed under aerobic conditions
• There is no net gain or loss of NAD⁺ in this process

Cori Cycle

• During strenuous exercise, lactate builds up in the muscle, leading to acidification that prevents continuous, strenuous work
• Lactate can be transported to the liver and converted to glucose and then transported back to the muscles
• The Cori cycle helps recycle NAD⁺ so that glycolysis can continue

Ethanol Fermentation by Yeast

• There is a two-step process needed to reduce pyruvate to ethanol
• Humans do not have pyruvate decarboxylase
• Humans express alcohol dehydrogenase for ethanol metabolism, but it is largely used in the reverse reaction
• The CO₂ is responsible for carbonation in beer and dough rising when baking bread
• Pyruvate decarboxylase requires Mg²⁺ and thiamine pyrophosphate.
• Alcohol dehydrogenase requires Zn²⁺ and NAD⁺.
• Pyruvate is decarboxylated to acetaldehyde in an irreversible first step

Ethanol Fermentation Reactions

• Glucose is fermented to ethanol and CO₂ in microorganisms rather than lactate
• Thiamine pyrophosphate (TPP) is an important coenzyme, tightly bound to pyruvate decarboxylase
• Acetaldehyde is reduced to ethanol in the second step by alcohol dehydrogenase with NADH
• Ethanol is toxic, and yeast die at ethanol concentrations of 12%

Ethanol and Lactate Fermentation

• There is no net change in the ratio of hydrogen to carbon atoms when glucose (H:C ratio = 12/6 = 2) is fermented to two ethanol and two CO₂ with a combined H:C ratio of 12/6 = 2
• As in lactate fermentation, there is no net change in the ratio of hydrogen to carbon atoms

Glycolysis - Overall Functions

• Glycolysis provides energy in the form of ATP
• Glycolysis generates intermediates for other pathways including the hexose monophosphate pathway, glycogen synthesis, fatty acid synthesis, and triglyceride synthesis
• Glucose 6-phosphate is utilized in the hexose monophosphate pathway to generate NADPH which is used in rapidly divided cells like bone marrow, skin, and intestinal mucosa
• NADPH is used to make RNA, DNA and the coenzymes ATP, NADH, FADH2, and coenzyme A
• One of the fates of pyruvate generates acetyl-CoA for use in the TCA cycle and oxidative phosphorylation

Glycolysis - Specific functions

• Red blood cells rely exclusively on glycolysis for energy
• Glycolysis provides energy in skeletal muscle during exercise, especially high-intensity
• Glycolysis provides a source of glycerol 3-phosphate for triglyceride synthesis in adipose and liver tissues
• Glycolysis provides a source of acetyl-CoA for fatty acid synthesis