Glycolysis, Kreb Cycle Electron Transport [PDF]

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STB1083 BIOCHEMISTRY

Lecture 13B GLYCOLYSIS, KREB CYCLE & ELECTRON TRANSPORT

Glycolysis • Glucose catabolism is carried out in all cells. • What happen to glucose molecule? - Glucose will initially undergo glycolysis. - Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate. - 3 final products – 2 Pyruvate molecules, 2 ATP and 2 NADH. • After glycolysis there are 3 possible fate for pyruvate: 1. Anaerobic glycolysis. 2. Aerobic oxidation. 3. Anaerobic fermentation.

Glycolysis

Glycolysis • There are two phases in glycolysis: i. Phase I - Preparative phase. • 6C sugar  3C sugar. ii. Phase II - ATP generating phase. • Produces energy (ATPs & NADHs) • The overall reaction of glycolysis: Glucose + 2 NAD+ + 2 ADP + 2 Pi  2 Pyruvate + 2 NADH + 2 ATP + 2 H2O + 2 H+ • There is a net gain of 2 ATP per glucose molecule. • As glucose is oxidized, 2 NAD+ are reduced to 2 NADH.

Glycolysis – The Fate of NADH and Pyruvate

Anaerobic Conditions 1. Lactic Acid Fermentation

2. Alcoholic Fermentation

Anaerobic Conditions • Alcoholic Fermentation and human consumption of ethanol.

Aerobic Respiration • When oxygen is present, most organisms will undergo two more steps, Kreb's Cycle, and Electron Transport, to produce their ATP. • In eukaryotes, these processes occur in the mitochondria, while in prokaryotes they occur in the cytoplasm.

Kreb’s Cycle (a.k.a Citric Acid Cycle) • Pyruvate is first altered in the transition reaction by removal of a carbon and two oxygens (which form carbon dioxide).

• When the carbon dioxide is removed, energy is given off, and NAD+ is converted into the higher energy form NADH. • Coenzyme A attaches to the remaining 2C (acetyl) unit, forming acetyl Co-A. This process is a prelude to the Kreb's Cycle. • Kreb’s Cycle is a cyclic process in that oxaloacetate reacts with acetyl CoA to form citrate to start a series of several other reactions. • The final reaction in the series involves the regeneration of oxaloacetate!

Kreb’s Cycle (a.k.a Citric Acid Cycle) • Between isocitrate and α-ketoglutarate, carbon dioxide is given off and NAD+ NADH. • Between α-ketoglutarate and succinyl-CoA the release of carbon dioxide and reduction of NAD+ into NADH happens again, resulting in a 4C chemical, succinate. • GTP (Guanine Triphosphate, which transfers its energy to ATP) is also formed here (GTP is formed by attaching a phosphate to GDP). • The remaining energy carrier-generating steps involve the shifting of atomic arrangements within the 4C molecules. • Between succinate and fumarate, the molecular shift releases not enough energy to make ATP or NADH, but this energy is captured by a new carrier, flavin adenine dinucleotide (FAD).

Kreb’s Cycle (a.k.a Citric Acid Cycle) • FAD is reduced by the addition of two H's to become FADH2.

• FADH2 is not as rich an energy carrier as NADH, yielding less ATP. • Between malate and oxaloacetate, energy is given off and trapped by the reduction of NAD+ to NADH. • In the last step, oxaloacetate reforms to complete the cycle. • The carbon dioxide released by cells is generated by the Kreb's Cycle, as are the energy carriers (NADH and FADH2) which play a role in the electron transport system.

Kreb’s Cycle (a.k.a Citric Acid Cycle) • The Kreb's cycle converts pyruvate to CO2, NADH, FADH2 and GTP/ATP.

• Overall Kreb Cycle reaction: 2 pyruvate + 2 GDP + 2 H3PO4 + 4 H2O + 2 FAD + 8 NAD+  6 CO2 + 2 GTP + 2 FADH2 + 8 NADH.

• The reduced energy is used to generate ATP using the electron transport chain in the presence of O2. • Frequently 36 ATP are produced. • In eukaryotic cells, NAD formed by glycolysis in the cytoplasm must be actively transported across the mitochondrial membrane.

• The cost of such active transport is one ATP for each NADH transported.

Electron Transport System (ETS) • While Kreb's Cycle occurs in the matrix of the mitochondrion, the Electron Transport System (ETS) chemicals are embedded in the membranes known as the cristae. • Kreb's cycle completely oxidized the carbons in the pyruvate, producing a small amount of ATP, and reducing NAD and FAD into higher energy forms (NADH and FADH) . • In the ETS those higher energy forms are used to produce ATP. • Cytochromes are molecules that pass the electrons along the ETS chain. • Energy released by the "downhill" passage of electrons is captured as ATP by ADP molecules. • The ADP is reduced to ATP by the gain of electrons via the process called oxidative phosphorylation.

Electron Transport System (ETS) • Oxidative phosphorylation is the gradient exchange of H+ ions across the inner mitochondrial membrane. • This mechanism is known as chemiosmotic coupling. - This involves both chemical and transport processes. • Drops in the potential energy of electrons moving down the ETS chain occur at three points. - These points turn out to be where ADP + Pi are converted into ATP. - Potential energy is captured by ADP and stored in the pyrophosphate bond.

Electron Transport System (ETS) • NADH enters the ETS chain at the beginning, yielding 3 ATP per NADH. • FADH2 enters at Co-Q, producing only 2 ATP per FADH2. • NADH and FADH2 carry protons (H+) and electron (e-) to the electron transport chain located in the membrane.

• Energy from the transfer of electrons along the chain transports protons across the membrane and creates an electrochemical gradient.

Electron Transport System (ETS) • As the accumulating protons follow the electrochemical gradient back across the membrane through an ATP synthase complex, the movement of the protons provides energy for synthesizing ATP from ADP and phosphate. • At the end of the ETS, 2 protons, 2 electrons, and half of an oxygen molecule combine to form water. • Since oxygen is the final electron acceptor, the process is called aerobic respiration.

Anaerobic Fermentation vs. Oxidative Phosphorylation • Anaerobic fermentation results in 2 ATP per glucose molecule. • Oxidative Phosphorylaltion can yield up to 38 ATP per glucose. • The rate of ATP production via anaerobic glycolysis can be up to 100 times faster than that of oxidative phosphorylation.

Anaerobic Fermentation vs. Oxidative Phosphorylation