Molecular Biology Wk 5

Question 1

What are the two ways in which animal cells make ATP

Answer 1

1.Certain energetically favorable, enzyme-catalyzed reactions involved in the breakdown of foods are directly coupled to the energetically unfavorable reaction ADP + Pi →ATP. Thus the oxidation of food molecules can provide energy for the immediate production of ATP.

2. In the second pathway to making ATP, the energy from other activated carriers is used to drive ATP production. This process, called oxidative phosphorylation, takes place on the inner mitochondrial membrane. These reactions produce both ATP and the additional activated carriers that will subsequently help drive the production of much larger amounts of ATP by oxidative phosphorylation.

Question 2

Look at GOODNOTES for diagram of mitochondria

Question 3

The breakdown of food molecules occurs in three stages

Answer 3

Stage 1 /also called digestion/ mostly occurs outside cells in the mouth and the gut— although intracellular lysosomes can also digest large organic molecules.

Stage 2 /a chain of reactions called glycolysis/ occurs mainly in the cytosol, except for the final step of conversion of pyruvate to acetyl groups on acetyl CoA, which occurs in the mitochondrial matrix.

Stage 3 begins with the citric acid cycle in the mitochondrial matrix and concludes with oxidative phosphorylation on the mitochondrial inner membrane. The NADH generated in stage 2 during glycolysis and the conversion of pyruvate to acetyl CoA—adds to the NADH produced by the citric acid cycle to drive the production of ATP by oxidative phosphorylation.

(B) The net products of the complete oxidation of food include ATP , NADH, CO2, and H2O. The ATP and NADH provide the energy and electrons needed for biosynthesis; the CO2 and H2O are waste products.

NADH - nicotinamide adenine dinucleotide hydride.

Question 4

The Citric Acid Cycle Generates the High-Energy Electrons Required for ATP Production

Answer 4

In eukaryotic cells, acetyl CoA is produced in the mitochondria from molecules derived from sugars and fats. Most of the cell’s oxidation reactions occur in these organelles, and most of its ATP is made here. The acetyl groups in acetyl CoA are then oxidized to CO2 via the citric acid cycle.

Question 5

Activated carriers generated during the citric acid cycle power the production of ATP

Answer 5

Pyruvate and fatty acids enter the mitochondrial matrix (bottom), where they are converted to acetyl CoA. The acetyl CoA is then metabolized by the citric acid cycle, which produces NADH (and FADH2, not shown). During oxidative phosphorylation, highenergy electrons donated by NADH - nicotinamide adenine dinucleotide hydride (and
FADH2) are then passed along the electrontransport chain in the inner membrane to oxygen (O2); this electron transport generates a proton gradient across the
inner membrane, which is used to drive the production of ATP by ATP synthase

for example, it requires four electrons from four NADH molecules to convert O2 to two H2O
molecules.

Question 6

Electron Transport Drives the Synthesis of the Majority of the ATP in Most Cells

Answer 6

In the oxidative phosphorylation the chemical energy captured by the activated carriers produced during glycolysis and the citric acid cycle is used to generate ATP. The most prominent of these reactions is the phosphorylation of ADP to generate ATP on the matrix side of the inner membrane (Figure). Oxidative phosphorylation occurs in both eukaryotic cells and in aerobic bacteria.

Question 7

Mitochondria catalyze a major conversion of energy

Answer 7

In oxidative phosphorylation, the energy released by the oxidation of NADH to NAD+ is harnessed— through energy- conversion processes in the
inner mitochondrial membrane—to drive the energy-requiring phosphorylation of ADP to form ATP

Question 8

High-energy electrons are transferred through three respiratory enzyme complexes in the inner mitochondrial membrane

Answer 8

During the transfer of high-energy electrons from NADH to oxygen (blue lines), protons derived from water are pumped across the membrane from the matrix into the intermembrane space by each of the complexes . Ubiquinone (Q) and cytochrome c (c) serve as mobile carriers that carry electrons from one complex to the next.

Question 9

Cell Respiration Is Amazingly Efficient
Table provides a full accounting of the ATP produced by the complete oxidation of glucose.

Answer 9

LOOK AT GOODNOTES

Question 10

Cells Obtain Most of Their Energy by a Membrane-based Mechanism

Answer 10

Membrane-based mechanisms use the energy provided by food or sunlight to generate ATP. The main chemical energy currency in cells is ATP. Small amounts of ATP are generated during glycolysis in the cytosol of all cells. But for the majority of cells, most of their ATP is produced by oxidative phosphorylation. The generation of ATP by oxidative phosphorylation differs from the way ATP is produced during glycolysis, in that it requires a membrane.

In eukaryotic cells, oxidative phosphorylation takes place in mitochondria, and it depends on an electron- transport process that drives the transport of protons (H+) across the inner mitochondrial membrane.

Question 11

The Evolution of Energy-Generating Systems

Answer 11

Oxidative phosphorylation might have evolved in stages:
Stage 1 could have involved the evolution of an ATPase that pumped protons out of the cell using the energy of ATP hydrolysis.

Stage 2 could have involved the evolution
of a different proton pump, driven by an electron-transport chain.

Stage 3 would then have linked these two systems together to generate an ATP synthase that uses the protons pumped by the electron-transport chain to synthesize ATP . A bacterium with this final system would have had a selective advantage over bacteria with neither of the systems or only one.

Question 12

Mitochondria most likely evolved from engulfed bacteria.

Answer 12

It is virtually certain that mitochondria originate from bacteria that were engulfed by an ancestral pre-eukaryotic cell and survived inside it, living in symbiosis with their host.

Note that the double membrane of presentday mitochondria is thought to have been derived from the plasma membrane and outer membrane of the engulfed bacterium.

Question 13

Chloroplasts almost certainly evolved from engulfed photosynthetic bacteria

Answer 13

Like mitochondria, chloroplasts contain their own DNA, reproduce by dividing in two, and are thought to have evolved from bacteria—in this case, from photosynthetic bacteria that were engulfed by an early eukaryotic cell.

Question 14

Mitochondria and chloroplasts share many of the features of their bacterial ancestors

Answer 14

Both organelles contain their own DNA-based genome and the machinery to copy this DNA and to make RNA and protein. The inner compartments of these organelles—the mitochondrial matrix and the chloroplast stroma—contain the DNA (red ) and a special set of ribosomes. Membranes in both organelles—the mitochondrial inner membrane and the chloroplast thylakoid membrane—contain the protein complexes involved in ATP production.

Question 15

describe the mitochondria

Answer 15

In individual mitochondrion is bounded by two highly specialized membranes— one surrounding the other. These membranes, called the outer and inner mitochondrial membranes, create two mitochondrial compartments: a large internal space called the matrix and a much narrower intermembrane space

Mitochondria are present in large numbers—1000 to 2000 in a liver cell, for example. But their numbers vary depending on the cell type and can change with the energy needs of the cell. In skeletal muscle cells, for example, mitochondria can divide until their numbers increase five- to tenfold if the muscle has been repeatedly stimulated to contract

Question 16

A mitochondrion is organized into four separate compartments

Question 17

Mitochondria Can Change Their Shape, Location, and Number to Suit a Cell’s Needs

Answer 17

Some cells, mitochondria remain fixed in one location, where they supply ATP directly to a site of unusually high energy consumption

Question 18

Molecular Organization and Gene Products of

Answer 18

Human mtDNA encodes :

Mitochondrial DNA
➢2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and 13 polypeptides essential to the oxidative respiration functions of the organelle.

➢Interesting observation is that in vertebrate mtDNA, the two strands vary in density, as revealed by centrifugation. This provides researchers with a way to isolate the strands for study, designating one heavy (H) and the other light (L). While most of the mitochondrial genes are encoded by the H strand, several are encoded by the complementary L strand. With only rare exceptions, introns are absent from mitochondrial genes, and gene repetitions are seldom present

Question 19

Size of mtDNA IM HUMANS

Answer 19

16.6 kb

Question 20

Gene products that are essential to mitochondrial function

Answer 20

●Replication in mitochondria is dependent on enzymes encoded by nuclear DNA.
●The majority of proteins that function in mitochondria are encoded by nuclear genes.
●While bacterial and nuclear RNA polymerases are known to be composed of numerous subunits, the mitochondrial variety consists of only one polypeptide chain. This polymerase is generally sensitive to antibiotics that inhibit bacterial RNA synthesis, but not to eukaryotic inhibitors.

Question 21

mitochondrial inheritance

Answer 21

In maternal effect, also referred to as maternal influence, an offspring’s phenotype for a particular trait is under the control of nuclear gene products present in the egg. The nuclear genes of the female gamete are transcribed, and the genetic products (either proteins or untranslated RNAs) accumulate in the egg cytoplasm. After fertilization, these products are distributed among newly formed cells and influence the patterns or traits established during early development. Three examples will illustrate such an influence of the maternal genome on particular traits.

Question 22

Mitochondrial disease

Answer 22

Mitochondrial diseases can affect almost any part of the body, including the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas.

Question 23


Mutations in Mitochondrial DNA Cause Human Disorders 
Myoclonic epilepsy with ragged-red fibers (MERRF)


Answer 23

Myoclonic epilepsy and ragged-red fiber disease (MERRF) demonstrates a pattern of inheritance consistent with maternal transmission. Analysis of mtDNA from patients with MERRF has revealed a mutation in one of the mitochondrial genes encoding a transfer RNA.

Ragged-red fibers in skeletal muscle cells from patients with the mitochondrial disease MERRF:
(a) The muscle fiber has mild proliferation of mitochondria. (See red rim and speckled cytoplasm.)
(b) Marked proliferation in which mitochondria have replaced most cellular structures.

Question 24

LOOK AT GOODNOTES FOR SYMPTOMS

Question 25

Leber hereditary optic neuropathy
 (LHON)

Answer 25

Leber’s hereditary optic neuropathy(LHON) is amitochondrially inherited(transmitted from mother to offspring) degeneration ofretinalganglion cells(RGCs) and theiraxonsthat leads to an acute or subacute loss of central vision; Vision loss occurs because the cells in theoptic nervedie.

Four mutations have been identified, all of which disrupt normal oxidative phosphorylation. LHON is usually due to point mutations in mitochondrialDNA. These mutations are atgene encoding a subunit of NADH dehydrogenase. / MT-ND1,MT-ND4,MT-ND4L, orMT-ND6/

Question 26

LHON MORE INFO

Answer 26

The average age of vision loss is 27, but onset is quite variable. Hereditary optic neuropathiescan be inherited as autosomaldominant, autosomalrecessive, and X-linked traits . Men cannot pass on the disease to their offspring. Affects predominantly young adult males.

Question 27

Kearns-Sayre syndrome

Answer 27

Kearns-Sayre syndromeis a condition that affects many parts of the body, especially the eyes. The features ofKearns-Sayre syndromeusually appear before age 20, and the condition is diagnosed by a few characteristic signs and symptoms. The most common deletion removes 4,997 nucleotides, which includes twelve mitochondrial genes. Deletions of mtDNA result in impairment of oxidative phosphorylation and a decrease in cellular energy production. Regardless of which genes are deleted, all steps of oxidative phosphorylation are affected. Individuals severely affected by Kearns– Sayre syndrome (KSS) lose their vision, experience hearing loss, and display heart conditions, ptosis.

Question 28

KSS

Answer 28

People withKearns-Sayre syndromemay also experience :
muscle weakness in their limbs,
deafness,
kidney problems,
deterioration of cognitive functions (dementia).
Affected individuals often have:
short stature.
In addition, diabetes mellitus is occasionally seen in people withKearns-Sayre syndrome.
The features ofKearns-Sayre syndromeusually appear before age 20

Question 29

Mitochondria, Human Health, and Aging

Answer 29

Mitochondrial dysfunction is implicated in most all major disease conditions, including Type II (late-onset) diabetes, atherosclerosis, neurodegenerative diseases such as Parkinson, Alzheimer, and Huntington disease, schizophrenia and bipolar disorders, and a variety of cancers.

The study of hereditary mitochondrial-based disorders has also suggested a link between the progressive decline of mitochondrial function and the aging process. It has been hypothesized that the accumulation of sporadic mutations in mtDNA leads to an increased prevalence of defective mitochondria (and the concomitant decrease in the supply of ATP) in cells over a lifetime. Many studies have now documented that aging tissue contain mitochondria with increased levels of DNA damage.

Question 30

Essential Concepts

Answer 30

Mitochondria, chloroplasts, and many prokaryotes generate energy by a membrane-based mechanism known as chemiosmotic coupling, which involves using an electrochemical proton gradient to drive the synthesis of ATP.

Mitochondria produce most of an animal cell’s ATP, using energy derived from oxidation of sugars and fatty acids.

Mitochondria have an inner and an outer membrane. The inner membrane encloses the mitochondrial matrix, where the citric acid cycle produces large amounts of NADH and FADH2 from the oxidation of acetyl CoA.

In the inner mitochondrial membrane, high-energy electrons donated by NADH and FADH2 pass along an electron-transport chain and eventually combine with molecular oxygen (O2) to form water.

Much of the energy released by electron transfers along the electrontransport chain is harnessed to pump protons (H+) out of the matrix, creating an electrochemical proton gradient. The proton pumping is carried out by three large respiratory enzyme complexes embedded in the inner membrane.

Question 31

Essential Concepts /cont./

Answer 31

• The electrochemical proton gradient across the inner mitochondrial membrane is harnessed to make ATP when protons move back into the matrix through an ATP synthase located in the inner membrane.

• The electrochemical proton gradient also drives the active transport of selected metabolites into and out of the mitochondrial matrix.

• Electron-transport chains associated with photosystems transfer high-energy electrons from water to NADP+ to form NADPH, which produces O2 as a by-product.

• Both mitochondria and chloroplasts are thought to have evolved from bacteria that were endocytosed by other cells. Each retains its own genome and divides by processes that resemble a bacterial cell division.

• Chemiosmotic coupling mechanisms are of ancient origin. Modern microorganisms that live in environments similar to those thought to have been present on the early Earth also use chemiosmotic coupling to produce ATP.

Question 32

A Mitochondrion is organised into 4 seperate compartments

Answer 32

matrix- highly concentrated mixture of hundreds of enzymes, including those required for the oxidation of pyruvate and fatty acids and for the citric acid cycle

inner membrane- folded into numerous cristae, inner membrane contains proteins that carry out OP including the ETC and ATP synthase that makes ATP

outer membrane- contains porins, the outer membrane is permeable to all molecules of 5000 daltons or less

intermembrane space- this space contains several enzymes that use ATP passing out of the matrix to phosphrylate other nucleotides.

In liver mitochondria, an estimated 67% of the total mitochondrial protein is located in the matrix, 21% in the inner membrane, 6% in the outer membrane, and 6% in the intermembrane space