Carbohydrate Metabolism: Glycolysis

• Carbohydrate metabolism involves glycolysis and the Krebs cycle.

Glycolysis

• Converts glucose (C6H12O6) into pyruvate through a sequence of ten reactions.
• These reactions involve ten intermediate compounds.
• Free energy released forms ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide).
• The most common type is the EMP pathway, other pathways include the Entner-Doudoroff pathway.
• Net reaction: Glucose + 2NAD + 2ADP → 2 Pyruvate + 2NADH + 2 ATP
• Glycolysis has a preparatory phase of five steps consuming energy to convert glucose into two Glyceraldehyde-3-phosphate molecules.
• The second half, called the pay-off phase, generates a net gain of ATP and NADH.
• Each pay-off phase reaction occurs twice per glucose molecule because glucose yields two triose sugars.
• This yields 2 NADH and 4 ATP molecules, resulting in a net gain of 2 NADH and 2 ATP per glucose molecule.

Sequence of Glycolysis Reactions

• Glucose is converted to Glucose-6-phosphate through the use of hexokinase, consuming ATP and producing ADP.
• Glucose-6-phosphate is converted to Fructose-6-phosphate by glucose phosphate isomerase.
• Fructose-6-phosphate becomes Fructose-1,6-bisphosphate via phosphofructokinase, consuming ATP and producing ADP.
• Fructose-1,6-bisphosphate: it's products via Aldolase are Glyceraldehyde-3-phosphate and Dihydroxy acetone phosphate that are isomers.
• Glyceraldehyde-3-phosphate can interconvert with Dihydroxy acetone phosphate with use of Triose phosphate.
• Glyceraldehyde-3-phosphate is converted to 1,3-bisphosphoglycerate via Glyceraldehyde 3-phosphate dehydrogenase,producing NADH.
• 1,3-bisphosphoglycerate becomes 3-phosphoglycerate via phosphoglycerate kinase which produces ATP.
• 3-phosphoglycerate is transformed into 2-phosphoglycerate with the use of phosphoglycerate mutase.
• 2-phosphoglycerate is converted to Phospheno pyruvate by Enolase
• Phospheno pyruvate is converted to pyruvate via Pyrivate kinase, yielding ATP

Importance of Glycolysis

• It's the initial process of carbohydrate catabolism.

It serves three principal functions:

• Generation of ATP and NADH as cellular energy in anaerobic respiration.
• Production of pyruvate for the citric acid cycle in aerobic respiration.
• Production of six- and three-carbon intermediate compounds for various cellular purposes.
• Glycolysis functions as the main energy source in prokaryotes, eukaryotic cells lacking mitochondria, and eukaryotic cells under low oxygen conditions.
• It is a universal metabolic process because it is the foundation of both aerobic and anaerobic respiration.

Regulation of Glycolysis

• Glycolysis is activated when ATP is needed.
• Glycolysis activity decreases when ATP levels are sufficient.

Control points:

• Hexokinase.
• PFK-1.
• Pyruvate kinase.
• Regulation influenced by glucagon and insulin.

Tricarboxylic Acid Cycle (Krebs Cycle/Citric Acid Cycle/TCA)

• It is a series of enzyme-catalyzed chemical reactions.
• It's centrally important in all living cells that use oxygen for cellular respiration.
• In eukaryotic cells, it takes place in the mitochondrial matrix.
• Chemical conversion of carbohydrates, fats, and proteins into carbon dioxide and water generates usable energy in aerobic organisms.
• The TCA cycle provides precursors for many compounds, including amino acids.

Overview of TCA Cycle

• A 4C compound, oxaloacetate, condenses with a 2C acetyl unit to form a 6C tricarboxylic acid, citrate.
• An isomer of citrate then goes under decarboxylation which yields a 5C compound, α-ketoglutarate.
• α-ketoglutarate (5C) is again decarboxylated to yield a 4C compound, succinate.
• Oxaloacetate is regenerated from succinate.
• Two carbon atoms enter the cycle as an acetyl unit, and two carbon atoms leave as two molecules of CO2.

TCA Cycle Steps

• Oxaloacetate, Acetyl CoA are converted in the presence of Citrate synthase to Citrate and CoA.
• Citrate is processed via Aconitase to Cis-aconitate.
• Cis-aconitate is processed via Aconitase to Iso-citrate.
• Isocitrate via Isocitrate dehydrogenase becomes α-ketoglutarate.
• a-ketoglutarate via a-ketoglutarate dehydrogenase yields Succinyl-CoA.
• Succinyl-CoA via Succinate thiokinase transforms to Succinate
• Succinate via Succinnate dehydrogenase yields Fumarate
• Fumarate via Fumarase transforms to Maleate
• Maleate via Maleate dehydrogenase transforms to Oxaloacetate

The Amphibolic Nature of TCA

• Used in both catabolic reactions to generate energy and anabolic reactions to generate metabolic intermediates for biosynthesis.
• Krebs cycle intermediates used for synthetic reactions need replenishment via anaplerotic reactions.

Regulation of Krebs Cycle

• Rate-controlling enzymes are citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.
• Activity is regulated by substrate availability, product inhibition, as well as allosteric inhibition or activation by other intermediates.

Difference Between Glycolysis and Krebs Cycle

• Glycolysis occurs in the cytoplasm.
• Krebs cycle takes place in the mitochondria.
• Glycolysis is a linear reaction consisting of 10 steps.
• The Krebs cycle is a cyclic reaction.
• Glycolysis starts with the phosphorylation of glucose.
• Krebs cycle starts with the joining of acetyl CoA and oxaloacetate.
• Glycolysis produces 2 ATP and 2 NADH.
• Krebs yields 3 NADH, 1 FADH, and 1 GTP.
• The last molecule formed in glycolysis is pyruvate.
• The last molecule formed in the cyclic Krebs is oxaloacetate.
• Glycolysis is mostly a catabolic pathway.
• Krebs cycle is an amphibolic pathway.