THE UNIVERSITY OF THE PEOPLE

BUSINESS ADMINISTRATION DEPARTMENT

BIOLOGY 1 FOR HEALTH STUDIES – ELECTIVE

METABOLISM

BIOL 1121- ASSIGNMENT ACTIVITY UNIT 4

4TH MAY, 2024

 CELLULAR RESPIRATION AND METABOLIC REGULATION

Introduction

Cellular respiration is a fundamental process in biology, encompassing a series of biochemical

reactions that convert nutrients into energy, primarily in the form of adenosine triphosphate

(ATP). At the heart of cellular respiration lie glycolysis, the citric acid cycle, and the electron

transport chain, orchestrated to extract energy from nutrients and synthesize ATP, the currency of

cellular energy (Lehninger et al., 2017). This essay embarks on a deep exploration of these

metabolic pathways, unraveling their mechanisms, regulation, and significance in cellular

function and survival.

1. Glycolysis: Initiating the Energy Harvest

Glycolysis is a fundamental pathway in cellular metabolism, serving as the initial step in glucose

catabolism. This process occurs in the cytoplasm and does not require oxygen, making it

essential for both aerobic and anaerobic conditions. Glycolysis involves a series of enzymatic

reactions that convert one molecule of glucose (a six-carbon sugar) into two molecules of

pyruvate (a three-carbon compound), along with the production of ATP and NADH (Nelson &

Cox, 2020). In aerobic conditions, pyruvate from glycolysis enters the mitochondria for further

breakdown, producing more ATP through oxidative phosphorylation. In anaerobic conditions,

pyruvate is converted to lactate or ethanol, generating ATP without oxygen but less efficiently.

The first phase of glycolysis involves the phosphorylation of glucose by hexokinase or

glucokinase, depending on the tissue. This step traps glucose within the cell by converting it to

glucose-6-phosphate. Subsequent reactions lead to the formation of fructose-6-phosphate and

then fructose-1,6-bisphosphate through the action of phosphofructokinase-1. This step is

considered a key regulatory point in glycolysis, as it is allosterically inhibited by high levels of

ATP and citrate, signaling that the cell has sufficient energy (Berg et al., 2002).

The second phase of glycolysis involves the cleavage of fructose-1,6-bisphosphate into two

three-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate

(G3P). These molecules interconvert via the enzyme triose phosphate isomerase, ultimately

leading to the production of two molecules of G3P.

In the final phase, each G3P molecule is oxidized to produce 1,3-bisphosphoglycerate, which

subsequently generates ATP and NADH. The conversion of 1,3-bisphosphoglycerate to 3-

phosphoglycerate and then to pyruvate completes glycolysis, yielding a net gain of two ATP

molecules per glucose molecule (Nelson & Cox, 2020).

Under aerobic conditions, pyruvate enters the mitochondria for further oxidation in the citric acid

cycle and oxidative phosphorylation. However, under anaerobic conditions, pyruvate is

converted to lactate or ethanol through fermentation pathways, allowing glycolysis to continue in

the absence of oxygen.

2. The Citric Acid Cycle: A Hub of Energy Metabolism

The citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a

central pathway in cellular respiration. It takes place in the mitochondrial matrix and serves as a

hub for energy metabolism, generating reducing equivalents in the form of NADH and FADH2,

as well as GTP, which can be converted to ATP. The citric acid cycle is crucial because it

generates energy-rich molecules like NADH and FADH2, which fuel the electron transport chain

for ATP production. It also provides intermediates for biosynthesis and regulates cellular

metabolism.
The cycle begins with the condensation of acetyl-CoA, derived from pyruvate oxidation, with

oxaloacetate to form citrate, catalyzed by citrate synthase. This step is an important regulatory

point, as citrate synthase is allosterically inhibited by high levels of ATP and NADH, indicating

that the cell has sufficient energy and does not need to produce more ATP through the citric acid

cycle (Alberts et al., 2002).

The subsequent steps of the citric acid cycle involve a series of redox reactions and substrate-

level phosphorylation events. NADH and FADH2 are generated through the oxidation of

isocitrate, α-ketoglutarate, succinate, fumarate, and malate. These reduced cofactors carry

electrons to the electron transport chain for ATP synthesis during oxidative phosphorylation.

The citric acid cycle also provides intermediates for biosynthetic pathways, such as amino acid

synthesis and the production of heme and nucleotides. Additionally, it plays a role in regulating

cellular metabolism by responding to energy demands and the availability of substrates.

3. The Electron Transport Chain: Powering ATP Synthesis

The electron transport chain (ETC) is a series of protein complexes and electron carriers located

in the inner mitochondrial membrane. It serves as the final stage of aerobic respiration,

transferring electrons from NADH and FADH2 to molecular oxygen, ultimately producing ATP

through oxidative phosphorylation (Lehninger et al., 2017).

The ETC operates through a series of redox reactions, with electrons flowing from higher to

lower energy states. NADH donates electrons to complex I (NADH dehydrogenase), while

FADH2 donates electrons to complex II (succinate dehydrogenase). Electrons are then passed

through complexes III (cytochrome c reductase) and IV (cytochrome c oxidase) before finally

reducing oxygen to water. The main electron carriers in the electron transport chain are NADH
and FADH2, which donate electrons to protein complexes in the inner mitochondrial membrane,

creating a proton gradient for ATP synthesis.

As electrons move through the ETC, protons are pumped across the inner mitochondrial

membrane, creating a proton gradient. This electrochemical gradient drives the synthesis of ATP-

by-ATP synthase, a process known as chemiosmosis (Alberts et al., 2002).

The regulation of the electron transport chain is tightly controlled to maintain cellular energy

homeostasis. Feedback mechanisms, such as the inhibition of complex I by high ATP levels, help

prevent excessive ATP production when energy demands are low.

4. ATP: The Molecular Currency of Cellular Energy

Adenosine triphosphate (ATP) is the primary energy currency of cells, playing a crucial role in

energy transfer and cellular processes. ATP synthesis occurs through oxidative phosphorylation,

where ATP synthase utilizes the proton gradient generated by the electron transport chain to

convert adenosine diphosphate (ADP) and inorganic phosphate (Pi) into ATP. Cells use ATP

because it's a more versatile and immediate source of energy compared to breaking down

carbohydrates directly. ATP stores and releases energy efficiently, making it suitable for cellular

processes requiring rapid energy supply.

ATP hydrolysis releases energy that drives cellular processes such as muscle contraction, active

transport, and biosynthesis (Lehninger et al., 2017). The hydrolysis of ATP to adenosine

monophosphate (AMP) and inorganic phosphate (Pi) is catalyzed by ATPases, which are

essential for cellular function and maintaining metabolic pathways.

ATP levels are tightly regulated by cellular energy demands and feedback mechanisms. High

ATP concentrations inhibit glycolytic enzymes and ATP synthase, promoting energy
conservation, while low ATP levels stimulate ATP production to meet cellular energy needs

(Lehninger et al., 2017).

Conclusion

cellular respiration and metabolic regulation form a complex yet harmonious symphony that

sustains life. Glycolysis, the citric acid cycle, the electron transport chain, and ATP synthesis

intricately collaborate to optimize energy production, metabolic flexibility, and cellular function

(Lehninger et al., 2017). Through this exploration, we gain a profound appreciation for the

molecular intricacies that underpin cellular metabolism and its essential role in organismal

survival.
Reference

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular biology

of the cell (4th ed.). Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK21054/

Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Biochemistry (5th ed.). W.H. Freeman and

Company. https://biokamikazi.wordpress.com/wp-content/uploads/2013/10/biochemistry-stryer-

5th-ed.pdf

Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2017). Lehninger Principles of Biochemistry

(7th ed.). W.H. Freeman and Company. http://aulanni.lecture.ub.ac.id/files/2012/01/15616949-

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