🦠Microbiology Unit 8 Review

Glycolysis and pyruvate oxidation are the first steps of carbohydrate catabolism. They break glucose down into a form that can feed into the Krebs cycle, generating a small amount of ATP along the way and producing the electron carriers that drive later energy production.

Glycolysis in Aerobic vs. Anaerobic Conditions

Glycolysis splits one glucose molecule into two pyruvate molecules in the cytoplasm. This process doesn't require oxygen at all, so it runs the same way regardless of whether oxygen is present.

Produces a net gain of 2 ATP and 2 NADH per glucose molecule
In aerobic conditions, pyruvate moves into the mitochondrial matrix, gets converted to acetyl-CoA, and enters the Krebs cycle for further oxidation
In anaerobic conditions, pyruvate is instead shunted into fermentation. This regenerates $NAD^+$ $N A D^{+}$ so glycolysis can keep running. The end product depends on the organism:
- Lactic acid fermentation (some bacteria, animal muscle cells): pyruvate → lactate
- Ethanol fermentation (yeast, some bacteria): pyruvate → ethanol + $CO_2$

The key point about fermentation is that it doesn't produce extra ATP. Its only job is to recycle $NAD^+$ so glycolysis doesn't stall.

Net Yields from Glycolysis

Glycolysis has two phases, and the ATP math works like this:

Preparatory phase (energy investment): 2 ATP are consumed to phosphorylate glucose and split it into two 3-carbon molecules
Payoff phase: 4 ATP are produced (2 per 3-carbon molecule) by substrate-level phosphorylation

Net ATP yield: $4 - 2 = 2$ ATP per glucose
NADH yield: 2 NADH per glucose (one produced per 3-carbon molecule during oxidation of glyceraldehyde-3-phosphate)
Carbon output: 2 pyruvate molecules (each with 3 carbons)

Pyruvate to Acetyl-CoA Conversion

Before pyruvate can enter the Krebs cycle, it must be converted to acetyl-CoA. This happens in the mitochondrial matrix and is catalyzed by the pyruvate dehydrogenase complex, a large multi-enzyme complex with three components: pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3).

The conversion involves four steps:

Decarboxylation: A carboxyl group is removed from pyruvate as $CO_2$ , leaving a 2-carbon fragment
Oxidation: The 2-carbon fragment is oxidized to an acetyl group
Transfer to CoA: The acetyl group is attached to coenzyme A, forming acetyl-CoA
$NAD^+$ reduction: $NAD^+$ picks up electrons, producing NADH

Overall reaction:

$Pyruvate + CoA + NAD^+ \rightarrow Acetyl\text{-}CoA + CO_2 + NADH$

Since each glucose produces 2 pyruvate molecules, this step generates 2 NADH and 2 $CO_2$ per glucose before the Krebs cycle even begins.

Krebs Cycle (Citric Acid Cycle)

The Krebs cycle completes the oxidation of glucose-derived carbon. Acetyl-CoA enters the cycle in the mitochondrial matrix, and its 2 carbons are fully oxidized to $CO_2$ . The cycle doesn't produce much ATP directly. Instead, it loads up electron carriers (NADH and $FADH_2$ ) that will deliver electrons to the electron transport chain.

Products and Yields of the Krebs Cycle

Each turn of the cycle processes one acetyl-CoA and produces:

3 NADH
1 $FADH_2$
1 GTP (equivalent to 1 ATP, produced by substrate-level phosphorylation)
2 $CO_2$

Oxaloacetate is regenerated at the end of each turn, ready to accept another acetyl group and start the cycle again. This is why it's called a cycle rather than a linear pathway.

Since one glucose yields 2 acetyl-CoA, the per-glucose totals from the Krebs cycle are:

Product	Per acetyl-CoA	Per glucose (×2)
NADH	3	6
$FADH_2$	1	2
GTP (ATP)	1	2
$CO_2$	2	4

Krebs Cycle in Cellular Biosynthesis

The Krebs cycle isn't just for energy. Several of its intermediates get pulled out and used as starting materials for biosynthesis. This is why the cycle is considered amphibolic, meaning it serves both catabolic and anabolic roles.

Key biosynthetic connections:

Oxaloacetate → aspartate, asparagine, pyrimidine nucleotides
α-Ketoglutarate → glutamate, glutamine, proline, arginine, purine nucleotides
Succinyl-CoA → heme and porphyrins
Citrate → fatty acids and steroids (citrate is exported to the cytoplasm and cleaved to provide acetyl-CoA for lipid synthesis)

When intermediates are siphoned off, the cycle would slow down unless they're replaced. Anaplerotic reactions solve this problem by replenishing cycle intermediates. The most important example: pyruvate carboxylase catalyzes $Pyruvate + CO_2 \rightarrow Oxaloacetate$ , feeding oxaloacetate directly back into the cycle.

Energy Production and Alternative Pathways

Electron Transport Chain and Oxidative Phosphorylation

The NADH and $FADH_2$ generated by glycolysis, pyruvate oxidation, and the Krebs cycle carry high-energy electrons to the electron transport chain (ETC), a series of protein complexes in the inner mitochondrial membrane (or plasma membrane in prokaryotes).

Electrons pass through the chain via a series of redox reactions, ultimately reducing $O_2$ to $H_2O$ . As electrons move down the chain, energy is released and used to pump protons ( $H^+$ ) across the membrane, creating a proton gradient. ATP synthase then uses this gradient to drive ATP production through chemiosmosis. This process, called oxidative phosphorylation, generates the vast majority of ATP from glucose catabolism.

Alternative Carbohydrate Pathways

Not all carbohydrate metabolism flows through glycolysis and the Krebs cycle. Two other pathways are worth knowing:

Pentose phosphate pathway (PPP): Branches off from glycolysis at glucose-6-phosphate. It produces NADPH (used for biosynthetic reductions and antioxidant defense) and ribose-5-phosphate (needed for nucleotide and nucleic acid synthesis). This pathway is especially active in cells with high biosynthetic demands.
Gluconeogenesis: The reverse direction of glucose production from non-carbohydrate precursors like pyruvate, lactate, glycerol, and certain amino acids. It's not simply glycolysis in reverse, since three irreversible glycolytic steps are bypassed by different enzymes.

🦠Microbiology Unit 8 Review