PCAT Exam: Biological Processes - Cellular and Molecular Biology

Cellular and Molecular Biology

Structure and Function of Cells
The cell is the main functional and structural component of all living organisms. Robert Hooke, an English scientist, coined the term “cell” in 1665. Hooke’s discovery laid the groundwork for the cell theory, which is composed of three principals:
1. All organisms are composed of cells.
2. All existing cells are created from other living cells.
3. The cell is the most fundamental unit of life.

Organisms can be unicellular (composed of one cell) or multicellular (composed of many cells). All cells must be bounded by a cell membrane, filled with cytoplasm of some sort, and coded by a genetic sequence.
The cell membrane separates a cell’s internal and external environments. It is a selectively permeable membrane, which usually only allows the passage of certain molecules by diffusion. Phospholipids and proteins are crucial components of all cell membranes. The cytoplasm is the cell’s internal environment and is aqueous, or water-based. The genome represents the genetic material inside the cell that is passed on from generation to generation.

Prokaryotes and Eukaryotes
Prokaryotes are primitive organisms and have been around for billions of years. Eukaryotes evolved from prokaryotes and are much more complex organisms.
Prokaryotic cells are much smaller than eukaryotic cells. The majority of prokaryotes are unicellular, while the majority of eukaryotes are multicellular. Prokaryotic cells have no nucleus, and their genome is found in an area known as the nucleoid. They also do not have membrane-bound organelles, which are “little organs” that perform specific functions within a cell.
Eukaryotic cells have a proper nucleus containing the genome. They also have numerous membrane-bound organelles such as lysosomes, endoplasmic reticula (rough and smooth), Golgi complexes, and mitochondria. The majority of prokaryotic cells have cell walls, while most eukaryotic cells do not have cell walls. The DNA of prokaryotic cells is contained in a single circular chromosome, while the DNA of eukaryotic cells is contained in multiple linear chromosomes. Prokaryotic cells divide using binary fission, while eukaryotic cells divide using mitosis. Examples of prokaryotes are bacteria and archaea while examples of eukaryotes are animals and plants.

Nuclear Parts of a Cell
Nucleus (plural nuclei): Houses a cell’s genetic material, deoxyribonucleic acid (DNA), which is used to form chromosomes. A single nucleus is the defining characteristic of eukaryotic cells. The nucleus of a cell controls gene expression. It ensures genetic material is transmitted from one generation to the next.
Chromosomes: Complex thread-like arrangements composed of DNA that is found in a cell’s nucleus. Humans have 23 pairs of chromosomes for a total of 46.
Chromatin: An aggregate of genetic material consisting of DNA and proteins that forms chromosomes during cell division.
Nucleolus (plural nucleoli): The largest component of the nucleus of a eukaryotic cell. With no membrane, the primary function of the nucleolus is the production of ribosomes, which are crucial to the synthesis of proteins.

Cell Membranes
Cell membranes encircle the cell’s cytoplasm, separating the intracellular environment from the extracellular environment. They are selectively permeable, which enables them to control molecular traffic entering and exiting cells. Cell membranes are made of a double layer of phospholipids studded with proteins. Cholesterol is also dispersed in the phospholipid bilayer of cell membranes to provide stability. The proteins in the phospholipid bilayer aid the transport of molecules across cell membranes.
Scientists use the term “fluid mosaic model” to refer to the arrangement of phospholipids and proteins in cell membranes. In that model, phospholipids have a head region and a tail region. The head region of the phospholipids is hydrophilic, which means it is attracted to water, while the tail region hydrophobic, or repelled by water. Because they are hydrophilic, the heads of the phospholipids are facing the water, pointing inside and outside of the cell. Because they are hydrophobic, the tails of the phospholipids are oriented inward between both head regions. This orientation constructs the phospholipid bilayer.


Cell membranes have the distinct trait of selective permeability. The fact that cell membranes are amphiphilic (having hydrophilic and hydrophobic zones) contributes to this trait. As a result, cell membranes are able to regulate the flow of molecules in and out of the cell.
Factors relating to molecules such as size, polarity, and solubility determine their likelihood of passage across cell membranes. Small molecules are able to diffuse easily across cell membranes compared to large molecules. Polarity refers to the charge present in a molecule. Polar molecules have regions, or poles, of positive and negative charge and are water soluble, while nonpolar molecules have no charge and are fat-soluble. Solubility refers to the ability of a substance, called a solute, to dissolve in a solvent. A soluble substance can be dissolved in a solvent, while an insoluble substance cannot be dissolved in a solvent. Nonpolar, fat-soluble substances have a much easier time passing through cell membranes compared to polar, water-soluble substances.

Passive Transport Mechanisms
Passive transport refers to the migration of molecules across a cell membrane that does not require energy. The three types of passive transport include simple diffusion, facilitated diffusion, and osmosis.
Simple diffusion relies on a concentration gradient, or differing quantities of molecules inside or outside of a cell. During simple diffusion, molecules move from an area of high concentration to an area of low concentration. Facilitated diffusion utilizes carrier proteins to transport molecules across a cell membrane. Osmosis refers to the transport of water across a selectively permeable membrane. During osmosis, water moves from a region of low solute concentration to a region of high solute concentration.

Active Transport Mechanisms
Active transport refers to the migration of molecules across a cell membrane that requires energy. It’s a useful way to move molecules from an area of low concentration to an area of high concentration. Adenosine triphosphate (ATP), the currency of cellular energy, is needed to work against the concentration gradient.
Active transport can involve carrier proteins that cross the cell membrane to pump molecules and ions across the membrane, like in facilitated diffusion. The difference is that active transport uses the energy from ATP to drive this transport, as typically the ions or molecules are going against their concentration gradient. For example, glucose pumps in the kidney pump all of the glucose into the cells from the lumen of the nephron even though there is a higher concentration of glucose in the cell than in the lumen. This is because glucose is a precious food source and the body wants to conserve as much as possible. Pumps can either send a molecule in one direction, multiple molecules in the same direction (symports), or multiple molecules in different directions (antiports).
Active transport can also involve the movement of membrane-bound particles, either into a cell (endocytosis) or out of a cell (exocytosis). The three major forms of endocytosis are: pinocytosis, where the cell is drinking and intakes only small molecules; phagocytosis, where the cell is eating and intakes large particles or small organisms; and receptor-mediated endocytosis, where the cell’s membrane splits off to form an internal vesicle as a response to molecules activating receptors on its surface.
Exocytosis is the inverse of endocytosis, and the membranes of the vesicle join to that of the cell’s surface while the molecules inside the vesicle are released outside. Exocytosis is common in nervous and muscle tissue for the release of neurotransmitters and in endocrine cells for the release of hormones. The two major categories of exocytosis are excretion and secretion. Excretion is defined as the removal of waste from a cell. Secretion is defined as the transport of molecules, such as hormones or enzymes, from a cell.

Structure and Function of Cellular Organelles
Organelles are specialized structures that perform specific tasks in a cell. The term literally means “little organ.” Most organelles are membrane-bound and serve as sites for the production or degradation of chemicals. The following are organelles found in eukaryotic cells:
 

Nucleus: As mentioned, a cell’s nucleus contains genetic information in the form of DNA. The nucleus is surrounded by the nuclear envelope. A single nucleus is the defining characteristic of eukaryotic cells. The nucleus is also the most important organelle of the cell. It contains the nucleolus, which manufactures ribosomes (another organelle), which are crucial in protein synthesis (also called gene expression).
Mitochondria: Mitochondria are oval-shaped and have a double membrane. The inner membrane has multiple folds called cristae. Mitochondria are responsible for the production of a cell’s energy in the form of adenosine triphosphate (ATP). ATP is the principal energy transfer molecule in eukaryotic cells. Mitochondria also participate in cellular respiration.
Rough Endoplasmic Reticulum: The rough endoplasmic reticulum (RER) is composed of linked membranous sacs called cisternae with ribosomes attached to their external surfaces. The RER is responsible for the production of proteins that will eventually get shipped out of the cell.
Smooth Endoplasmic Reticulum: The smooth endoplasmic reticulum (SER) is composed of linked membranous sacs called cisternae without ribosomes, which distinguishes it from the RER. The SER’s main function is the production of carbohydrates and lipids, which can be created expressly for the cell or to modify the proteins from the RER that will eventually get shipped out of the cell.
Golgi Apparatus: The Golgi apparatus is located next to the SER. Its main function is the final modification, storage, and shipment of products (proteins, carbohydrates, and lipids) from the endoplasmic reticulum.
Lysosomes: Lysosomes are specialized vesicles that contain enzymes capable of digesting food, surplus organelles, and foreign invaders such as bacteria and viruses. They often destroy dead cells in order to recycle cellular components. Lysosomes are only found in animal cells.
Secretory Vesicles: Secretory vesicles transport and deliver molecules into or out of the cell via the cell membrane. Endocytosis refers to the movement of molecules into a cell via secretory vesicles. Exocytosis refers to the movement of molecules out of a cell via secretory vesicles.
Ribosomes: Ribosomes are not membrane-bound. They are responsible for the production of proteins as specified from DNA instructions. Ribosomes can be free or bound.
Cilia and Flagella: Cilia are specialized hair-like projections on some eukaryotic cells that aid in movement, while flagella are long, whip-like projections that are used in the same capacity.

Here an illustration of the cell:


 
The following organelles are not found in animal cells:
Cell Walls: Cell walls can be found in plants, bacteria, and fungi, and are made of cellulose, peptidoglycan, and lignin, and other substances, depending on the organism it surrounds. Each of these substances is a type of sugar recognized as a structural carbohydrate. The carbohydrates are rigid structures located outside of the cell membrane. Cell walls function to protect the cell, maintain the cell’s shape, and provide structural support. The prevent over-expansion of the cell by excess water.
Vacuoles: Plant cells have central vacuoles, which are essentially a membrane surrounding a body of water. They may store nutrients or waste products. Since vacuoles are large, they also help to support the structure of plant cells.
Chloroplasts: Chloroplasts are membrane-bound organelles that perform photosynthesis. They contain structural units called thylakoids. Chlorophyll, a green pigment that circulates within the thylakoids, harnesses light energy (sunlight) and helps convert it into chemical energy (glucose).

Gene Expression
Genes are the basis of heredity. The German scientist Gregor Mendel first suggested the existence of genes in 1866. A gene can be pinpointed to a locus, or a particular position, on DNA. It is estimated that humans have approximately 20,000 to 25,000 genes. For any particular gene, a human inherits one copy from each parent for a total of two.

Genotypes and Phenotypes
Genotype refers to the genetic makeup of an individual within a species. Phenotype refers to the visible characteristics and observable behavior of an individual within a species.
Genotypes are written with pairs of letters that represent alleles. Alleles are different versions of the same gene, and, in simple systems, each gene has one dominant allele and one recessive allele. The letter of the dominant trait is capitalized, while the letter of the recessive trait is not capitalized. An individual can be homozygous dominant, homozygous recessive, or heterozygous for a particular gene. Homozygous means that the individual inherits two alleles of the same type, while heterozygous means that one dominant allele and one recessive allele have been inherited.
If an individual has homozygous dominant alleles or heterozygous alleles, the dominant allele is expressed. If an individual has homozygous recessive alleles, the recessive allele is expressed. For example, a species of bird develops either white or black feathers. The white feathers are the dominant allele, or trait (A), while the black feathers are the recessive allele (a). Homozygous dominant (AA) and heterozygous (Aa) birds will develop white feathers. Homozygous recessive (aa) birds will develop black feathers.

Influence of Phenotype on Genotype
An individual’s genotype is determined by the genetic material (DNA) inherited from the individual’s parents. Natural selection leads to adaptations within a species, which affects the phenotype. Over time, individuals within a species with the most advantageous phenotypes will survive and reproduce. As result of reproduction, the subsequent generation of phenotypes receives the fittest genotype. Eventually, the individuals within a species with genetic fitness flourish and those without it die out without passing on their traits. As explained above, this is also referred to as the concept of “survival of the fittest.” When this process is duplicated over numerous generations, the outcome is offspring with a level of genetic fitness that meets or exceeds that of their parents.

Cell Division and Growth
Cell replication in eukaryotes involves duplicating the genetic material (DNA) and then dividing to yield two daughter cells, which are clones of the parent cell. The cell cycle is a series of stages leading to the growth and division of a cell. The cell cycle helps to replenish damaged or depleted cells. On average, eukaryotic cells go through a complete cell cycle every 24 hours. Some cells such as epithelial, or skin, cells are constantly dividing, while other cells such as mature nerve cells do not divide. Prior to mitosis, cells exist in a non-divisional stage of the cell cycle called interphase. During interphase, the cell begins to prepare for division by duplicating DNA and its cytoplasmic contents. Interphase is divided into three phases: gap 1 (G1), synthesis (S), and gap 2 (G2).

DNA Replication
Replication refers to the process during which DNA makes copies of itself. Enzymes govern the major steps of DNA replication.


The process begins with the uncoiling of the double helix of DNA. Helicase, an enzyme, accomplishes this task by breaking the weak hydrogen bonds uniting base pairs. The uncoiling of DNA gives rise to the replication fork, which has a Y-shape. Each separated strand of DNA will act as a template for the production of a new molecule of DNA. The strand of DNA oriented toward the replication fork is called the leading strand and the strand oriented away from the replication fork is named the lagging strand.
Replication of the leading strand is continuous. DNA polymerase, an enzyme, binds to the leading strand and adds complementary bases. Replication of the lagging strand of DNA, on the other hand, is discontinuous. DNA polymerase produces discontinuous segments, called Okazaki fragments, which are later joined together by another enzyme, DNA ligase. To start the DNA synthesis on the lagging strand, the enzyme primase lays down a strip of RNA, called an RNA primer, to which the DNA polymerase can bind. As a result, two clones of the original DNA emerge from this process. DNA replication is considered semiconservative due to the fact that half of the new molecule is old, and the other half is new.

Cell Differentiation
Cell differentiation refers to the process of a cell transforming into another type of cell. It most commonly involves a less specialized cell transforming into a more specialized cell.
The human body contains a vast array of cells, which undergo division and differentiation to compose each unique human being. The trillions of cells composing the human body are derived from one cell, a fertilized egg called a zygote. The zygote not only divides, but also differentiates into cells that perform specific tasks.
Genes control the process of cell differentiation during human development. The zygote divides through mitosis into a blastula and then into a gastrula. At this stage, the three embryonic germ layers (endoderm, mesoderm, and ectoderm) are formed. Most of the human body systems develop from one or more of the embryonic germ layers. For example, the digestive system develops from the endoderm, or innermost germ layer; the cardiovascular system develops from the mesoderm, or middle germ layer; and the nervous system develops from the ectoderm, or outer germ layer.

Mitosis
Mitosis, or asexual reproduction, produces two new cells that are genetically identical to the parent cell. It can happen in virtually every healthy adult cell, although some cells like red blood cells and neurons do not divide in general. When a cell is not undergoing cell division, it is in a stage called interphase which is characterized by growth, typical maintenance, and DNA synthesis in the nucleus. Each healthy human cell nucleus typically has 46 chromosomes and is said to be diploid (2n), as this count comes from 23 pairs of homologous chromosomes. Homologous chromosomes are pairs of chromatids with similar sections that correspond to similar genes, as in pairs of chromosome 1 or pairs of chromosome 21.
Mitosis is divided into the following events:


Prophase: The already-duplicated chromatin condenses to form chromosomes. Each new chromosome is made up of two identical sister chromatids joined by a structure called a centromere. The nuclear envelope is degraded and spindle fibers form and attach to structures called centrioles. The centrioles separate and proceed to opposite poles of the cell.
Pro-metaphase: The centrioles build spindle fibers and attach them to the chromosomes.
Metaphase: Using tension from spindle fibers, the chromosomes align in the middle of the cell.
Anaphase: The spindle fibers contract and separate the chromosomes at their centromere. The single chromatids, pulled by the spindle fibers, begin migrating to opposite poles of the cell.
Telophase: The chromatids arrive at opposite poles of the cell. The spindle fibers disappear, the nuclear envelope reforms, and the chromosomes uncoil back into chromatin.
Cytokinesis: This process refers to the cleaving of the cytoplasm to form two daughter cells genetically identical to the parent cell. In animal cells, this happens via a cleavage furrow; a cleavage furrow is a pinching of the cell membrane near the center that deepens until it reaches the point that the cell membrane can recombine and split the entity into two separate cells.

Meiosis
Meiosis, or sexual division, happens only in specialized sex cells, and it produces four cells called gametes. In humans, sex cells are found in the ovaries and in the testes, and are in contrast to somatic cells, which constitute the rest of the body of the organism. Each gamete contains half the number of chromosomes of a normal cell, and each is said to be haploid (n), rather than diploid (2n). In humans, a gamete has 23 chromosomes instead of the 46 that are typically found in somatic cells. The female gamete is called an egg and the male gamete is called a sperm.
Preceding meiosis, the DNA is synthesized, and the chromatin coalesces into chromosomes, as in mitosis. However, the pairs of sister chromatids that are homologous combine together, joining their centromeres into a single chiasma and forming a tetrad. At this point, sections of the different chromatids may break off and rejoin, possibly in another place. Half of a leg of one chromatid may swap with that of another chromatid; the chromatids essentially exchange some of their genes with one another. This process, called crossing over or genetic recombination, happens in prophase I and leads to greater genetic diversity.


Like mitosis, meiosis is divided into the stages of prophase, metaphase, anaphase, telophase, and cytokinesis. However, as the end products have half the genetic material as the end products of mitosis, another round of division is needed. Therefore, meiosis is first partitioned into meiosis I and meiosis II, each round similar in scope to mitosis. During meiosis I, homologous chromosome pairs are separated into two daughter cells. Each daughter cell is haploid (n) because, although each cell at the end of meiosis I has 46 chromatids, half of them are duplicates of the other and not considered unique genetic material.


After cytokinesis I, the daughter cells immediately enter prophase II, rather than duplicating DNA or entering interphase. The nucleus disintegrates, the centrioles migrate to the ends of the cell, and the next round of divisions begins. This results in four haploid (n) daughter cells, the gametes of egg and sperm referenced earlier.
A common problem that arises in both meiosis and mitosis, but is especially noticeable in meiosis, is that of nondisjunction. Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate during anaphase. This causes the daughter cells to have one more or one fewer chromosomes than usual, which can ultimately result in genetic conditions like Down’s syndrome, when a meiotic egg with nondisjunction is fertilized.

Energy Transformations
There is a fundamental law of thermodynamics (the study of heat and movement) called Conservation of Energy. This law states that energy cannot be created nor destroyed, but rather, energy is transferred to different forms.
One biological example of energy transformation can be seen in photosynthesis. Photosynthesis is the process of converting light energy into chemical energy that is then stored in sugar and other organic molecules. It can be divided into two stages: the light-dependent reactions and the Calvin cycle. In plants, the photosynthetic process takes place in the chloroplast. Inside the chloroplast are membranous sacs, called thylakoids. Chlorophyll is a green pigment that lives in the thylakoid membranes and absorbs the light energy, starting the process of photosynthesis. The Calvin cycle takes place in the stroma, or inner space, of the chloroplasts.

The complex series of reactions that take place in photosynthesis can be simplified into the following equation:
6CO2 + 12H2O + Light Energy → C6H12O6 + 6O2 +6H2O.

Basically, carbon dioxide and water combine with light energy inside the chloroplast to produce organic molecules, oxygen, and water. Note that water is on both sides of the equation. Twelve water molecules are consumed during this process and six water molecules are newly formed as byproducts.

The Light Reactions
During the light reactions, chlorophyll molecules absorb light energy, or solar energy. In the thylakoid membrane, chlorophyll molecules, together with other small molecules and proteins, form photosystems, which are made up of a reaction-center complex surrounded by a light-harvesting complex. In the first step of photosynthesis, the light-harvesting complex from photosystem II (PSII) absorbs a photon from light, passes the photon from one pigment molecule to another within itself, and then transfers it to the reaction-center complex. Inside the reaction-center complex, the energy from the photon enables a special pair of chlorophyll a molecules to release two electrons. These two electrons are then accepted by a primary electron acceptor molecule. Simultaneously, a water molecule is split into two hydrogen atoms, two electrons, and one oxygen atom. The two electrons are transferred one by one to the chlorophyll a molecules, replacing their released electrons. The released electrons are then transported down an electron transport chain by attaching to the electron carrier plastoquinone (Pq), a cytochrome complex, and then a protein called plastocyanin (Pc) before they reach photosystem I (PS I). As the electrons pass through the cytochrome complex, protons are pumped into the thylakoid space, providing the concentration gradient that will eventually travel through ATP synthase to make ATP (like in aerobic respiration).
PS I absorbs photons from light, similar to PS II. However, the electrons that are released from the chlorophyll a molecules in PS I are replaced by the electrons coming down the electron transport chain (from PS II). A primary electron acceptor molecule accepts the released electrons in PS I and passes the electrons onto another electron transport chain, involving the protein ferredoxin (Fd). In the final steps of the light reactions, electrons are transferred from Fd to Nicotinamide adenine dinucleotide phosphate (NADP+) with the help of the enzyme NADP+ reductase and NADPH is produced. The ATP and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) produced from the light reactions are used as energy to form organic molecules in the Calvin cycle.

The Calvin Cycle
There are three phases in the Calvin cycle: carbon fixation, reduction, and regeneration of the CO2 acceptor. Carbon fixation is when the first carbon molecule is introduced into the cycle, when CO2 from the air is absorbed by the chloroplast. Each CO2 molecule enters the cycle and attaches to ribulose bisphosphate (RuBP), a five-carbon sugar. The enzyme RuBP carboxylase-oxygenase, also known as rubisco, catalyzes this reaction. Next, two three-carbon 3-phosphoglycerate sugar molecules are formed immediately from the splitting of the six-carbon sugar.
Next, during the reduction phase, an ATP molecule is reduced to ADP and the phosphate group attaches to 3-phosphoglycerate, forming 1,3-bisphosphoglycerate. An NADPH molecule then donates two high-energy electrons to the newly formed 1,3-bisphosphate, causing it to lose the phosphate group and become glyceraldehyde 3-phosphate (G3P), which is a high-energy sugar molecule. At this point in the cycle, one G3P molecule exits the cycle and is used by the plant. However, to regenerate RuBP molecules, which are the CO2 acceptors in the cycle, five G3P molecules continue in the cycle. It takes three turns of the cycle and three CO2 molecules entering the cycle to form one G3P molecule.
In the final phase of the Calvin cycle, three RuBP molecules are formed from the rearrangement of the carbon skeletons of five G3P molecules. It is a complex process that involves the reduction of three ATP molecules. At the end of the process, RuBP molecules are again ready to enter the first phase and accept CO2 molecules.
Although the Calvin cycle is not dependent on light energy, both steps of photosynthesis usually occur during daylight, as the Calvin cycle is dependent upon the ATP and NADPH produced by the light reactions, because that energy can be invested into bonds to create high-energy sugars. The Calvin cycle invests nine ATP molecules and six NADPH molecules into every one molecule of G3P that it produces. The G3P that is produced can be used as the starting material to build larger organic compounds, such as glucose.



Metabolism
Metabolism is the set of chemical processes that occur within a cell for the maintenance of life. It includes both the synthesizing and breaking down of substances. A metabolic pathway begins with a molecule and ends with a specific product after going through a series of reactions, often involving an enzyme at each step. An enzyme is a protein that aids in the reaction. Catabolic pathways are metabolic pathways in which energy is released by complex molecules being broken down into simpler molecules. Opposite to catabolic pathways are anabolic pathways, which use energy to build complex molecules out of simple molecules. With cell metabolism, remember the first law of thermodynamics: Energy can be transformed, but it cannot be created or destroyed. Therefore, the energy released in a cell by a catabolic pathway is used up in anabolic pathways.
The reactions that occur within metabolic pathways are classified as either exergonic reactions or endergonic reactions. Exergonic reactions end in a release of free energy, while endergonic reactions absorb free energy from its surroundings. Free energy is the portion of energy in a system, such as a living cell, that can be used to perform work, such as a chemical reaction. It is denoted as the capital letter G, and the change in free energy from a reaction or set of reactions is denoted as delta G (ΔG). When reactions do not require an input of energy, they are said to occur spontaneously. Exergonic reactions are considered spontaneous because they result in a negative delta G (–ΔG), where the products of the reaction have less free energy within them than the reactants. Endergonic reactions require an input of energy and result in a positive delta G (+ΔG), with the products of the reaction containing more free energy than the individual reactants. When a system no longer has free energy to do work, it has reached equilibrium. Since cells must always do work, they are no longer alive if they reach equilibrium.
Cells balance their energy resources by using the energy from exergonic reactions to drive endergonic reactions forward, a process called energy coupling. Adenosine triphosphate, or ATP, is a molecule that is an immediate source of energy for cellular work. When it is broken down, it releases energy used in endergonic reactions and anabolic pathways. ATP breaks down into adenosine diphosphate, or ADP, and a separate phosphate group, releasing energy in an exergonic reaction. As ATP is used up by reactions, it is also regenerated by having a new phosphate group added onto the ADP products within the cell in an endergonic reaction.
Enzymes are special proteins that help speed up metabolic reactions and pathways. They do not change the overall free energy release or consumption of reactions; they just make the reactions occur more quickly because they lower the activation energy required for the reaction to occur. Enzymes are designed to act only on specific substrates. Their physical shape fits snugly onto their matched substrates, so enzymes only speed up reactions that contain the substrates to which they are matched.

Cellular Respiration
Cellular respiration is a set of metabolic processes that converts energy from nutrients into ATP. Respiration can either occur aerobically, using oxygen, or anaerobically, without oxygen. While prokaryotic cells carry out respiration in the cytosol, most of the respiration in eukaryotic cells occurs in the mitochondria.

Aerobic Respiration
There are three main steps in aerobic cellular respiration: glycolysis, the citric acid cycle (also known as the Krebs cycle), and oxidative phosphorylation.

Glycolysis is an essential metabolic pathway that converts glucose to pyruvate and allows for cellular respiration to occur. It does not require oxygen to be present. Glucose is a common molecule used for energy production in cells. During glycolysis, two three-carbon sugars are generated from the splitting of a glucose molecule. These smaller sugars are then converted into pyruvate molecules via oxidation and atom rearrangement. Glycolysis requires two ATP molecules to drive the process forward, but the end product of the process has four ATP molecules, for a net production of two ATP molecules. Also, two reduced nicotinamide adenine dinucleotide (NADH) molecules are created from when the electron carrier oxidized nicotinamide adenine dinucleotide (NAD+) peels off two electrons and a hydrogen atom.

In aerobically-respiring eukaryotic cells, the pyruvate molecules then enter the mitochondrion. Pyruvate is oxidized and converted into a compound called acetyl-CoA. This molecule enters the citric acid cycle to begin the process of aerobic respiration.

The citric acid cycle has eight steps. Remember that glycolysis produces two pyruvate molecules from each glucose molecule. Each pyruvate molecule oxidizes into a single acetyl-CoA molecule, which then enters the citric acid cycle. Therefore, two citric acid cycles can be completed and twice the number of ATP molecules are generated per glucose molecule.
 

Step 1: Acetyl-CoA adds a two-carbon acetyl group to an oxaloacetate molecule and produces one citrate molecule.
Step 2: Citrate is converted to its isomer, isocitrate, by removing one water molecule and adding a new water molecule in a different configuration.
Step 3: Isocitrate is oxidized and converted to α-ketoglutarate. A carbon dioxide (CO2) molecule is released and one NAD+ molecule is converted to NADH.
Step 4: α-Ketoglutarate is converted to succinyl-CoA. Another carbon dioxide molecule is released and another NAD+ molecule is converted to NADH.
Step 5: Succinyl-CoA becomes succinate by the addition of a phosphate group to the cycle. The oxygen molecule of the phosphate group attaches to the succinyl-CoA molecule and the CoA group is released. The rest of the phosphate group transfers to a guanosine diphosphate (GDP) molecule, converting it to guanosine triphosphate (GTP). GTP acts similarly to ATP and can actually be used to generate an ATP molecule at this step.
Step 6: Succinate is converted to fumarate by losing two hydrogen atoms. The hydrogen atoms join a flavin adenine dinucleotide (FAD) molecule, converting it to FADH2, which is a hydroquinone form.
Step 7: A water molecule is added to the cycle and converts fumarate to malate.
Step 8: Malate is oxidized and converted to oxaloacetate. One lost hydrogen atom is added to an NAD molecule to create NADH. The oxaloacetate generated here then enters back into step one of the cycle.

At the end of glycolysis and the citric acid cycles, four ATP molecules have been generated. The NADH and FADH2 molecules are used as energy to drive the next step of oxidative phosphorylation.



Oxidative Phosphorylation
Oxidative phosphorylation includes two steps: the electron transport chain and chemiosmosis. The inner mitochondrial membrane has four protein complexes, sequenced I to IV, used to transport protons and electrons through the inner mitochondrial matrix. Two electrons and a proton (H+) are passed from each NADH and FADH2 to these channel proteins, pumping the hydrogen ions to the inner-membrane space using energy from the high-energy electrons to create a concentration gradient. NADH and FADH2 also drop their high-energy electrons to the electron transport chain. NAD+ and FAD molecules in the mitochondrial matrix return to the Krebs cycle to pick up materials for the next delivery. From here, two processes happen simultaneously:
 

1. Electron Transport Chain: In addition to complexes I to IV, there are two mobile electron carriers present in the inner mitochondrial membrane, called ubiquinone and cytochrome C. At the end of this transport chain, electrons are accepted by an O2 molecule in the matrix, and water is formed with the addition of two hydrogen atoms from chemiosmosis.
 

2. Chemiosmosis: This occurs in an ATP synthase complex that sits next to the four electron transporting complexes. ATP synthase uses facilitated diffusion (passive transport) to deliver protons across the concentration gradient from the inner mitochondrial membrane to the matrix. As the protons travel, the ATP synthase protein physically spins, and the kinetic energy generated is invested into phosphorylation of ADP molecules to generate ATP. Oxidative phosphorylation produces twenty-six to twenty-eight ATP molecules, bringing the total number of ATP generated through glycolysis and cellular respiration to thirty to thirty-two molecules.

Anaerobic Respiration
Some organisms do not live in oxygen-rich environments and must find alternate methods of respiration. Anaerobic respiration occurs in certain prokaryotic organisms. They utilize an electron transport chain similar to the aerobic respiration pathway; however, the terminal acceptor molecule is an electronegative substance that is not O2. Some bacteria, for example, use the sulfate ion (SO42-) as the final electron accepting molecule and the resulting byproduct is hydrogen sulfide (H2S), instead of water.
Muscle cells that reach anaerobic threshold go through lactic acid respiration, while yeasts go through alcohol fermentation. Both processes only make two ATP.