Cell Structure Exam 3

Cellular respiration

harvests the energy remaining in pyruvate and NADH from glycolysis, it uses an external electron acceptor to oxidize substrates completely to CO2

Stages of aerobic respiration

1. Glycolytic pathway

2. Pyruvate is oxidized to generate acetyl CoA

3. The Citric Acid Cycle

4. Electron transport

5. Oxidative phosphorylation

Mitochondrial myopathies

human diseases caused by defects in mitochondrial functions

Oxygen

The terminal electron acceptor in aerobic respiration

Water

the reduced form in aerobic respiration

Which type of respiration yieldsmore energy

Aerobic respiration

Where are mitochondria frequently clustered?

in regions of cells with the greatest need for ATP (ex. muscle cells)

Mitochondria outer membrane

contains porins that allow passage of solutes with molecular weights up to 5000

Mitochondria intermembrane space

the space between the inner and outer membranes

Mitochondria inner membrane

the most permeable to most solutes, partitioning the mitochondrion into two separate compartments, the intermembrane and the mitochondrial matrix

Cristae

infoldings on the inner membrane of the mitochondria, increase surface area of the inner membrane and provide more space for electron transport to take place

Transit sequences

targeting signals located on the N-terminal of a polypeptide

Transit peptidase

enzymes that remove the transit sequence once the polypeptide has arrived

Special transport complexes

located on the outer and inner membrane of the mitochondria and allow for uptake of polypeptide chains

Pores for transport

TOM (translocase of the outer membrane)

TIM (translocase of the inner membrane)

Transit sequence receptors

component of transport complex that recognizes transit sequences

Chaperone proteins

bind polypeptides targeted to the mitochondria to help maintain the unfolded state

Mechanism of import of polypeptides into the mitochondrial matrix

1. Hsp70 chaperone proteins bind to the polypeptide and help with unfolding

2. TOM transit sequence receptor binds to the N-terminus of the polypeptide

3. Chaperone proteins are released, and ATP is hydrolyzed as the polypeptide moves through the TOM and TIM pores

4. Transit sequence is removed by transit peptidase in the matrix as soon as the transit sequence enters the matrix

5. Mitochondrial Hsp70 chaperone proteins bind polypeptide as it enters the matrix

6. Often, mitochondrial Hsp60 chaperone proteins bind the polypeptide and assist in proper folding

Citric Acid Cycle/TCA Cycle/Krebs cycle

Each round involves the entry of two carbons, the release of two CO2, and the regeneration of oxaloacetate, pyruvate is converted to acetyl coenzyme A—bridging the reaction

How is pyruvate converted to acetyl CoA

Pyruvate dehydrogenase complex (PDH)

Substrates of TCA

CoA, NAD+, FAD, and ADP

Products of TCA

NADH, FADH2, CO2, and ATP

Allosteric inhibitors of TCA

NADH, ATP, and acetyl CoA

These activate at least one regulator enzyme in the cycle

NAD+, ADP, and AMP

Electron transport

transfer of electrons from reduced cofactors (NADH, FADH2) to oxygen

Electron transport chain (ETC)

a multistep process involving an ordered series of reversibly oxidized electron carriers functioning together to carry out electron transfer (contains a number of integral membrane proteins that are found in the inner mitochondrial membrane)

Which complexes are found in the inner mitochondrial membrane?

Complexes I, III, and IV

Complex I (NADH coenzyme Q oxidation complex/NADH dehydrogenase)

transfers electrons from NADH to CoQ, when 2 electrons are transferred, 4 protons are pumped across the membrane

Complex II (succinate—coenzyme Q oxidoreductase complex/succinate dehydrogenase)

transfers electrons from succinate to FAD (generating FADH2; this is reaction CAC-6), the electrons are transferred through 3 Fe-S centers to CoQ, no protons are pumped during this reaction

Complex III (cytochrome complex/ coenzyme Q—cytochrome c oxidoreductase complex)

accepts electrons from CoQ and transfers them to cytochrome c, two cytochromes are prominent components, when 2 electrons are transferred, 4 protons are pumped across the membrane

Complex IV (cytochrome c oxidase)

electrons transfer from cytochrome c to an Fe atom in the heme A cofactor of cytochrome a then to cytochrome a3, there are 2 copper atoms which receive one electron, 4 electrons are needed to reduce O2 to H2O, 2 protons are pumped across the membrane for each electron pair

Which complex is the terminal oxidase?

complex IV transfers electrons directly to oxygen

What are the genes encoded by mitochondrial DNA

Complex I, II, III, and IV proteins, tRNAs, mitochondrial rRNA

Which compounds contribute to cellular aging?

Superoxide anion (O2-)

Hydrogen peroxide (H2O2)

antioxidants

soak up highly reactive oxidants and prevent cellular damage

Electrochemical proton gradient

the crucial link between electron transport and ATP production, drives ATP synthesis, ATP synthesis is coupled to electron transport

Chemiosmotic coupling model

the essential feature is that the link between electron transport and ATP formation is the electrochemical potential across a membrane, the electrochemical potential is created by pumping protons across a membrane as electrons transferred through the respiratory complexes

Proton translocator

the channel through which protons flow across the membrane (F₀)

F₀

provides a channel for exergonic flow of protons across the membrane, acts as a proton translocator, has 2 b subunits and 10 c subunits

F₁

carries out the ATP synthesis, driven by the energy of the proton gradient, has 3 alpha and 3 beta subunits plus 1 delta, 1 gamma, and one sigma subunit

ATP synthase

F₀ and F₁

Binding change model (Paul Boyer)

proposed that each of the 3 beta subunits of the F1 complex progresses through 3 different conformations

Conformations of the model

L (for loose), which binds ADP and P_i loosely

T (for tight), which binds ADP and P_i tightly and catalyzes the formation of ATP

O (for open), with little affinity for either substrates or product

Components of the endomembrane system

Endoplasmic reticulum

Golgi complex

Endosomes

Lysosomes

Peroxisomes

Endoplasmic reticulum

involved in protein synthesis and sorting

Rough ER

characterized by ribosomes on the cytosolic side of the membrane (form large flattened sheets)

the site for membrane synthesis, the folding of polypeptides, recognition and removal of misfolded proteins, assembly of multimeric proteins, and the initial steps of addition of carbohydrates to glycoproteins

Smooth ER

lacks ribosomes and has other roles in the cell involving the processing and storage of nonproteins (form tubular structures)

its functions include drug detoxification, glycogen breakdown, calcium storage, and steroid biosynthesis

Hydroxylation

adding hydroxyl groups to hydrophobic drugs to increase their solubility, making them easier to excrete from the body

Cytochrome P-450

catalyzes hydroxylation

How does hydroxylation occur?

via electron transport

Pharmacogenetics

investigates how inherited differences in genes, like P-450 can lead to differential responses to drugs and medications

Sarcoplasmic reticulum

a part of the smooth ER that specializes in calcium storage

Hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase

the committed step in cholesterol biosynthesis, founded in the smooth ER of liver cell

Statins

drugs that lower cholesterol, target HMG-CoA

What synthesizes phosphatidylethanolamine?

Mitochondria

What synthesizes cholesterol?

Peroxisomes

Phospholipid translocators (flippases)

transfer fatty acids for membrane proteins to the lumenal side of the bilyaer

Phospholipid exchange proteins

convey specific phospholipids to the mitochondria, chloroplasts, or peroxisomes

protein tags

target the proteins to a transport vesicle that will take it to the correct location

What is the first step in the pathway for delivering proteins to various locations in the endomembrane system?

Cotranslational import

Signal hypothesis

for polypeptides destined for the ER, the N-terminus contains an ER signal sequence that directs ribosome-mRNA-polypeptide complexes to the surface of the RER, then as the polypeptide chain elongates, it progressively crosses the ER membrane and enters the ER lumen

Components of amino acid sequences

15-30 amino acids long

positively charged N-terminal region

central hydrophobic region

polar region next to the cleavage site

Sorting signals

a linear sequence of amino acids that direct proteins to specific locations in the cell

Signal recognition particle (SRP)

recognizes and binds to the ER signal sequence and the binds to the ER membrane

The SRP Mechanism of Cotranslational import

1. mRNA binds to a free ribosome. The polypeptide is synthesizd until the ER signal sequence has been formed

2. SRP binds the ER signal sequence and blocks translation

3. The SRP binds to the ribosome to a translocon in the ER membrane

What is the translocon composed of?

SRP receptor

Ribosome receptor

Pore protein

Signal peptidase

SRP receptor

binding site for the SRP

Ribosome receptor

holds the ribosome in place

Pore protein

forms a channel for the growing polypeptide to enter the ER lumen

Signal peptidase

an enzyme to remove the ER signal sequence

Stop transfer sequence

halts translocation of the polypeptide through the ER membrane and the rest of the polypeptide stays on the cytosolic side of the ER membrane, moves laterally forming a permanent transmembrane segment

Start transfer sequence

the SRP binds and targets to the ER membrane, its hydrophobic region functions as a membrane anchor

Molecular chaperones

facilitate folding and assembly of polypeptides into multisubunit proteins

BiP

an Hsp70 chaperone protein, binds the hydrophobic region of a polypeptide which prevents aggregation

Golgi complex

involved in processing and sorting

Endosomes

carry and sort material brought into the cell

Lysosomes

digest ingested material and unneeded cellular components

Peroxisomes

involved in lipid metabolism and scavenging of reactive oxygen species