Week 4: Cell Metabolism Part 1

fermentation

purpose: to regenerate NAD+ so that glycolysis can continue producing ATP in the absence of oxygen

• occurs during intense exercise where oxygen may be lacking but the body still needs energy from glycolysis

uses NADH to turn pyruvate into lactate and leaves behind the required NAD

PFK (phosphofructokinase)

most important regulator of glycolysis

activated by:

• AMP / ADP: signals of low energy in the body

• Fructose 2, 6-biphosphate: binding to PFK and increasing its affinity for its substrate, fructose-6-phosphate (F6P)

inhibited by:

• ATP: body has too much energy

• low pH: caused by lactate

• citrate: produced in citric acid cycle and too much citrate shows that the cell is already producing enough ATP through the cycle

gluconeogenesis

a reversal of glycolysis, pyruvate turns into glucose, occurs in the liver

acetyl coa in allosteric regulation of pyruvate carboxylase

• The reason acetyl-CoA activates pyruvate carboxylase is that it signals high energy status in the cell. When acetyl-CoA levels are high, it indicates that the cell is ready to produce glucose (via gluconeogenesis) because energy is plentiful, and pyruvate carboxylase needs to generate oxaloacetate for the gluconeogenesis pathway.

• Without acetyl-CoA, the cell may be in a low-energy state, so the body will prioritize other pathways (such as glycolysis or fatty acid synthesis) over gluconeogenesis.

Cori Cycle

The lactate produced in muscle during heavy exercise can:

1. Be taken up by some tissues (e.g. heart) converted to pyruvate and used for energy (TCA cycle)

2. Be transported to the liver – and converted to glucose (Cori cycle)

pyruvate dehydrogenase complex

an enzyme complex that plays a crucial role in cellular metabolism. It acts as a link between glycolysis (the breakdown of glucose) and the citric acid cycle

• The enzyme complex catalyzes the conversion of pyruvate into acetyl-CoA by removing a carbon atom from pyruvate (in the form of CO₂). This process is called decarboxylation.

• The remaining two-carbon molecule is then attached to coenzyme A (CoA) to form acetyl-CoA, which is the key molecule for the citric acid cycle.

• During the conversion, NAD+ (nicotinamide adenine dinucleotide) is reduced to NADH, which carries electrons to the electron transport chain to produce ATP

TCA Cycle

complete oxidation of the C atoms on acetyl CoA (lost as CO2)

• acetyl CoA (2C) condenses with 4C oxaloacetate to form citric acid (6C)

• following 8 reactions (4 oxidation) oxaloacetate is regenerated

• produces 3 NADH, 1 FADH2, 1 GTP

control of the TCA Cycle

isocitrate dehydrogenase

stimulated:

• ADP

• NAD+

• isocitrate

inhibited:

• ATP

• NADH

a-ketoglutarate dehydrogenase

stimulated:

• ADP

inhibited:

• succinyl CoA

• ATP

• NADH

anapleurosis

reactions that replenish TCA cycle intermediates