6_Cellular Energetics: Mitochondria and Cell Respiration

cellular respiration

• process which the opposite of photosynthesis

• oxidative phosphorylation and substrate-level phosphorylation

mitochondria

where biological process of such as Krebs Cycle and electron-transport chain, takes place in this "energy producing" structure within the cell.

Metabolism

• entails all chemical reactions that occur within the cell, including formation of energy.

• is an ultimate activity which involves series of these enzymatic reactions contributing to the sum of cellular activities that must be performed by the cell

anabolic and catabolic pathway

metabolic pathways involve 2 general types:

Anabolic pathway

Which metabolic pathway?

• for synthesis or production of cellular components or an increase in molecular order (decreased entropy)

• create or increase molecular order

• decreased entropy /endergonic (energy-requiring)

• polymer synthesis

• stored energy / fuels

• Ex: Glycogenesis and Starch formation; Glucogenesis (reduction of carbon)

Catabolic pathway

Which metabolic pathway?

• for breakdown of cell constituents into simpler molecules or monomers or a decrease in molecular order (increased entropy)

• breakdown into simplified molecules

• increased entropy / exergonic (energy-liberating)

• monomer synthesis / metabolite (small,organic molec.) synthesis

• energy release / fuel degradation

• Degradative pathway; Decrease in molecular order (high S)

oxygen

In catabolic pathway, the involvement of ___also matters, whether the breakdown of a substrate is under the aerobic (presence) or anaerobic (absence) of ___.

ATP (adenosine triphosphate)

• has been regarded as the universal energy coupler, found virtually in all cells, that this energy molecule stands as the primary energy "currency" in living cells.

• role in cellular energy transactions is carried out by its natural molecular structure that when it releases its energy, the __ hydrolysis liberates the outermost phosphate group (Pi).

• The __ bonds connecting the phosphate groups are called phosphoanhydride bonds.

• Crucial to cellular functions (growth and repair processes, or catabolic rxns. releasing energy to drive the anabolic reactions) have an efficient linking, or coupling, of energy-yielding processes to energy-requiring processes.

• It is the primary energy “currency” of the biological world, involved in most cellular energy transactions. Virtually in all cells, this phosphorylated compound is most commonly used as an energy intermediate, where cells store chemical energy.

phosphoanhydride bonds

• The ATP bonds connecting the phosphate groups are called ___

• These bonds are referred to as high-energy or energy-rich bonds, that when they are catabolized (by hydrolysis), the water molecules break this bond and liberates or releases free energy or (-) G or Gibbs energy (increase entropy), which is an exergonic reaction.

superior

The groups ___  to ATP can donate phosphate group to ADP such as PEP and form a new ATP.,

below

those __ATP means that these groups can accept phosphate groups from ATP and form phosphorylated glucose

between or -7.3 kcal/mol

ATP lies in ___  in exergonic release of Pi and becomes +7.3 kcal/mol upon addition or restoration of phosphate group.

+7.3 kcal/mol

ATP lies in between or -7.3 kcal/mol in exergonic release of Pi and becomes ___  upon addition or restoration of phosphate group.

phosphate group

ATP lies in between or -7.3 kcal/mol in exergonic release of Pi and becomes +7.3 kcal/mol upon addition or restoration of ___

group transfer reactions

• Transferring phosphate groups or movement of a chemical group from 1 molecule to another is called ___

• This process is common in energy metabolism and one of the most common processes in cellular metabolism

Anaerobic condition

• without oxygen or low oxygen supply, yields a ATP by fermentation process and Lactate is one of the common end-products/ in some organisms, or Ethanol + Carbon dioxide can also be yielded by other organisms called anaerobes.

• partial degradation in low or O2 lacking conditions (Glycolysis, Fermentation)

Aerobic condition

(+) of oxygen, yields ATP from oxidizable nutrients / substrates and complete catabolism yields carbon dioxide + water. The ATP yield under this condition, per 1 glucose molecule is 20x more higher than anaerobic conditions.

Chemotrophic energy metabolism

• involves reactions and pathways in cells that breaks down nutrients and conserve ATP, whereby, the food or nutrients taken in the body are used to meet the energy requirements of the body.

• This energy metabolism involves oxidation process that removes electrons under the presence of oxygen.

oxidation

Chemotrophic energy metabolism involves ___ process that removes electrons under the presence of oxygen.

reduction

the opposite of oxidation that gains electrons, which is an endergonic reaction.

protons

Commonly, in biological reductions and oxidations, the transfer of electrons are accompanied by __

Proton donor ; Electron acceptor

one is defined as____  (involves oxidation) and the other one is ___  (involves reduction)

NAD+

in NAD+ + 2H+ --> NADH + H+, which is the oxidized form (proton donor)

NADH

• in NAD+ + 2H+ --> NADH + H+, which is the reduced form (electron acceptor)

• In aerobic organisms: ____produced in Glycolysis & Krebs Cycle is reoxidized via the respiratory chain, with production of much additional ATP.

Nicotinamide NAD+

is a derivative of niacin (vitamin B5), it is an important coenzyme essential in the diet.

FAD and CoA

• Another Vitamin B derivatives are ___.

• The role of these important coenzymes in their reduced forms such as NADH and FADH are essential in ATP equivalents and yields in substrate-level phosphorylation, NADH = 3ATP and FADH = 2ATP.

NADH and FADH

Another Vitamin B derivatives are FAD and CoA. The role of these important coenzymes in their reduced forms such as ___are essential in ATP equivalents and yields in substrate-level phosphorylation

3 ; 2

Another Vitamin B derivatives are FAD and CoA. The role of these important coenzymes in their reduced forms such as NADH and FADH are essential in ATP equivalents and yields in substrate-level phosphorylation, NADH = __ATP and FADH = _ATP.

GLUCOSE (C6H12O6)

• one of the most important oxidizable substrates in energy metabolism is ___

• is the main sugar in the blood, we usually acquire them from dietary polysaccharides such as sucrose or starch, or in our stored polysaccharide the glycogen in our liver and muscles.

• In plants, ___is acquired from starch breakdown

sucrose or starch

Glucose (glc.) is the main sugar in the blood, we usually acquire them from dietary polysaccharides such as

glycogen

Glucose (glc.) is the main sugar in the blood, we usually acquire them from dietary polysaccharides such as sucrose or starch, or in our stored polysaccharide the ___in our liver and muscles

starch breakdown

In plants, glucose is acquired from ____especially, in vascular plants that largely conducts sucrose, glucose takes a half of the catabolized disaccharide: sucrose --> glucose + fructose.

Fructolysis

• metabolism of fructose

• in the intestines is broken down into GAP (glyceraldehyde-3-phosphate) can be used as a substrate for gluconeogenesis.

gluconeogenesis

• Fructolysis (metabolism of fructose) in the intestines is broken down into GAP (glyceraldehyde-3-phosphate) can be used as a substrate for ___

• Another process is that when cells, need glucose and other carbohydrates for other purposes, this process is called "____" (formation of new glucose) not from the usual glycogen or starch synthesis.

glucose and fructose

Both ___as simple sugars in our body can be good sources of cellular energy or ATP.

GLYCOLYSIS

• is a 10-step enzymatic reaction where 1 glucose molecule is simplified into pyruvic acid, with 1 oxidative reaction (Gly-6 or formation of Phosphoglyceraldehyde or PGAL) and generation of 2 ATP steps in (Gly-7 and Gly-10 reactions)

• is not only the principal route for glucose metabolism, but also the provides the main pathway for the metabolism of fructose and galactose.

• It can provide ATP in the absence of oxygen: Important for skeletal muscles; leads to Fatigue

• Lactic acidosis

• Phase 1: Preparation & Cleavage

• Phase 2: Oxidation & ATP Generation

• Phase 3: Pyruvate formation & ATP Generation

The Overview of glycolysis has 3 Phases:

Phase 1: Preparation & Cleavage

What Phase of Overview of Glycolysis?

• In the preparation, 2 molecules of ATP is also invested. Glucose (6C) is phosphorylated twice by ATP (Gly-1 and Gly-3) and splits to form 2 PGAL or G3P (Gly-5)

Phase 2: Oxidation & ATP Generation

What Phase of Overview of Glycolysis?

• Each PGAL are oxidized to 3-phosphoglycerate (Gly-7). Some of the ATP energy in this step is conserved and 2 NADH (Gly-6) are produced.

Phase 3: Pyruvate formation & ATP Generation

What Phase of Overview of Glycolysis?

• 2 molecules of 3-phosphoglycerate are converted to pyruvate (Gly-10) + 2 ATP (Gly-10)

fermentation

In the absence of oxygen, ____takes place with glucose --> lactate (lactic acid fermentation) or glucose --> ethanol + CO2 (alcoholic fermentation)

inorganic electron acceptors

Anaerobic respiration, uses ____ such as elemental sulfur, H+ ions and Fe3+ ions.

Obligate aerobes

organisms that perform whether aerobic or anaerobic respiration with glucose metabolism are then categorized into three types:

• oxygen (final electron acceptor), including us, humans.

Obligate anaerobes

organisms that perform whether aerobic or anaerobic respiration with glucose metabolism are then categorized into three types:

• inorganic substances: S, H+ and Fe3+ (final electron acceptor), many bacteria (lactic acid bacteria, methane producers, in deep-punctured wounds and gangrene and food poisoning)

Facultative anaerobes

organisms that perform whether aerobic or anaerobic respiration with glucose metabolism are then categorized into three types:

• can function under aerobic or anaerobic conditions (under oxygen then they can perform as fully aerobic, in the absence or low oxygen, they perform fermentation), species accounted to be facultative are many bacteria, fungi and some tissues such as skeletal muscles).

phophorolysis

The mobilization of these polysaccraides are called ____, which resembles hydrolysis but uses inorganic phosphate instead of water to break the alpha (1->4) glycosidic bond between successive glucose units liberating them as glucose-1 phosphate (G1P as monomers) and can be converted to G6P in glycolysis, without input of ATP.

inorganic phosphate

The mobilization of these polysaccraides are called phophorolysis, which resembles hydrolysis but uses ____ instead of water to break the alpha (1->4) glycosidic bond between successive glucose units liberating them as glucose-1 phosphate (G1P as monomers) and can be converted to G6P in glycolysis, without input of ATP.

alpha (1->4) glycosidic bond

The mobilization of these polysaccraides are called phophorolysis, which resembles hydrolysis but uses inorganic phosphate instead of water to break the ____  between successive glucose units liberating them as glucose-1 phosphate (G1P as monomers) and can be converted to G6P in glycolysis, without input of ATP.

LIVER and KIDNEYS

gluconeogenesis in all organisms and in animals occurs in the ____

pyruvic acid or lactic acid (fermentation)

Cells can synthesize glucose from 3C or 4C precursors that are non-carbohydrate in nature, and the common starting material as converted will be ____

3C or 4C precursors

Cells can synthesize glucose from ____  that are non-carbohydrate in nature, and the common starting material as converted will be pyruvic acid or lactic acid (fermentation)

CORI CYCLE

• the link between glycolysis in muscles and gluconeogenesis in the liver

• Lactate from muscles goes into the bloodstream towards the Liver, where lactate is reoxidized to pyruvate. And pyruvate will be the starting point for gluconeogenesis, then generates glucose and will be supplied in the blood.

• This prevents lactic acid accumulation in the muscles that may cause muscle cramps.

Mitochondria

• Site of Krebs and ETC

• This organelle accomplishes all reactions of TCA cycle, electron transport and oxidative phosphorylation.

outer mitochondrial membrane, intermembranous space, inner mitochondrial membrane

This double-membraned organelle (mitochondria) possess 3 regions and 2 separate compartments:

outer mitochondrial membrane

Mitochondria possess 3 regions and 2 separate compartments: (which one?)

• is more permeable and allows ions and small molecules (<5000Mw) through its porins/channel proteins

intermembranous space

Mitochondria possess 3 regions and 2 separate compartments: (which one?)

• is continuous to the cytosol allowing free movement of small solutes, while enzymes targeted to inner mitochondrial membrane are sequestered here and other soluble proteins are too large to pass through porin channels,

inner mitochondrial membrane 

Mitochondria possess 3 regions and 2 separate compartments: (which one?)

• is a selective membrane that possess long membrane infoldings called cristae that increases its surface area to accommodate many protein complexes for ETC and ATP synthesis defining the mitochondrion's capacity of ATP generation.

cytosol

intermembranous space is continuous to the ___ allowing free movement of small solutes

Cristae

• inner mitochondrial membrane is a selective membrane that possess long membrane infoldings called ___

• increases its surface area to accommodate many protein complexes for ETC and ATP synthesis defining the mitochondrion's capacity of ATP generation

• also has intercristal spaces allowing proton accumulation during ETC.

cristal junctions

The spaces in cristae are connected to inner mitochondrial membrane by ____ but allows limited diffusion of materials forming the 3rd enclosed region.

outer membrane to intermembranous space

1st region of mitochondria: _____ - external boundary

external boundary

1st region of mitochondria: outer membrane to intermembranous space - ____

intermembranous space and inner membrane

2nd region: _______ - inner boundary

inner boundary

2nd region: intermembranous space and inner membrane - ___

intermembranous space and intercristal space

3rd region: __________- innermost region

innermost region

3rd region: intermembranous space and intercristal space - ____

Matrix enzymes

• The interior of the mitochondrion is filled with semi-fluid matrix, containing ____ , mitoDNA (mDNA), ribosomes and proteins (imported from cytoplasm).

• are involved in pyruvate oxidation, TCA cycle, beta-oxidation of fats and amino acid catabolism

F1 complexes

The intermediates for ETC are organized into complexes:

• protruding from inner membrane to the matrix

• are involved in ATP synthesis, each complex consists of several polypeptides

Fo complex

The intermediates for ETC are organized into complexes:

• o for oligomycin, due to its sensitivity to the antibiotic,

• consists of hydrophobic polypeptides embedded within the inner membrane.

FoF1 complex, a.k.a, FoF1 ATP synthase

Together, they form ______ and accounts for major ATP generation in mitochondria and bacterial/prokaryotic cells, which is driven by proton electrochemical-gradient

proton electrochemical-gradient

Together, they form FoF1 complex, a.k.a, FoF1 ATP synthase and accounts for major ATP generation in mitochondria and bacterial/prokaryotic cells, which is driven by ___

Cellular respiration

involves the flow of electrons through a membrane, from reduced coenzymes to an external electron acceptor, usually accompanied by ATP generation or ATP yield.

NADH in glycolysis, FAD (flavin adenine dinucleotide), and coenzyme Q (ubiquinone)

These coenzymes collect electrons that pass them on to a series of electron carriers and until to the “final” electron acceptor, with ATP generation in the process

reduced form of oxygen

Water is formed as a ___, being the final electron acceptor

Cytosol

The central role of Mitochondrion in cell respiration:

• glucose oxidation and other sugars takes place in glycolysis

Cytosol, Under oxygen supply, TCA/Krebs cycle, ETC, Oxidative Phosphorylation

The central role of Mitochondrion in cell respiration:

Under oxygen supply,

The central role of Mitochondrion in cell respiration:

• pyruvate traverses inner mitochondrial membrane & is further oxidized into acetyl CoA (substrate in Krebs cycle)

TCA /Krebs cycle

The central role of Mitochondrion in cell respiration:

• ____complete oxidation of acetyly CoA to CO2 and reduced coenzymes NADH and FADH conserves most of the energy.

ETC (electron transport chain)

The central role of Mitochondrion in cell respiration:

• where reduced coenzymes shuttles the electrons to oxygen and in an exergonic reaction, coupled to the active transport (pumping) of protons across the inner mitochondrial membrane.

• The pumping of protons provides the exergonic energy for the continuous electron-shuttling of coenzyme carriers and creates an electrochemical gradient along the membrane.

oxidative phosphorylation

The central role of Mitochondrion in cell respiration:

• The energy of proton gradient drives ATP synthesis by ATP synthase in a process known as ___

KREBS CYCLE

• This pathway was elucidated in the laboratory of Hans Krebs thereby an honorary name for tricarboxylic acid cycle (TCA cycle).

• For all aerobic chemotrophs, this has a central feature in energy metabolism

citrate, succinate and oxaloacetate

3 carboxylic acids in the KREBS CYCLE are:

Pyruvate decarboxylation (pyruvate dehydrogenase, PDH)

gave rise to Acetyl CoA (2C), as the starting point

Acetyl CoA (2C)

Pyruvate decarboxylation (pyruvate dehydrogenase, PDH) gave rise to ___, as the starting point

oxaloacetate (4C)

Regardless of its origin, Acetyl CoA transfers its acetate group to____ to form citrate (6C), and then, successive 2 decarboxylations and several oxidations regenerates oxaloacetate (4C) again that will accept again the new 2 incoming acetyl CoA.

citrate (6C)

Regardless of its origin, Acetyl CoA transfers its acetate group to oxaloacetate (4C) to form __, and then, successive 2 decarboxylations and several oxidations regenerates oxaloacetate (4C) again that will accept again the new 2 incoming acetyl CoA.

2 decarboxylations

Regardless of its origin, Acetyl CoA transfers its acetate group to oxaloacetate (4C) to form citrate (6C), and then, successive ___ and several oxidations regenerates oxaloacetate (4C) again that will accept again the new 2 incoming acetyl CoA.

2 incoming acetyl CoA

Regardless of its origin, Acetyl CoA transfers its acetate group to oxaloacetate (4C) to form citrate (6C), and then, successive 2 decarboxylations and several oxidations regenerates oxaloacetate (4C) again that will accept again the new ____

citrate synthase

TCA-1: 2C-Acetyl CoA is incorporated to 4C-oxaloacetate to form 6C-citrate by

TCA-1

2C-Acetyl CoA is incorporated to 4C-oxaloacetate to form 6C-citrate by citrate synthase

TCA-2

citrate is converted to isocitrate (6C) by aconitase. Isocitrate has an easy oxidizable hydroxyl group for TCA-3

TCA-3

• the 1st oxidation/dehydrogenation reaction

• : Isocitrate is oxidized by isocitrate dehydrogenase to a 6C oxalosuccinate (unstable compound and not shown), with NAD+ as e-acceptor.

• Oxalosuccinate is immediately converted to alpha-ketoglutarate (5C) by decarboxylation, which is the 1st decarboxylation step (liberating inorganic CO2).

• alpha-keto acids like pyruvate and alpha-ketoglutarate have similar reactions

TCA-4

alpha-ketoglutarate (5C) to succinyl CoA (4C) is the 2nd decarboxylation step (liberating inorganic CO2), by alpha-ketoglutarate dehydrogenase

TCA-5

• Succinyl CoA to Succinate (by succinyl CoA synthetase), direct generation of GTP (or ATP) occurs in this one-step cycle, GTP and ATP are energy equivalents (ATP is bacterial cells & plant mitochondria and GTP in animal mitochondria).

• Thus, the net result of succinyl CoA hydrolysis is one molecule of ATP is generated.

TCA-6

the Succinate (4C) is formed and is oxidized to fumarate (4C), by succinate dehydrogenase, a unique reaction in which both electrons are from adjacent carbon atoms (C=C bonds)

succinate dehydrogenase

TCA-6: the Succinate (4C) is formed and is oxidized to fumarate (4C), by ____, a unique reaction in which both electrons are from adjacent carbon atoms (C=C bonds)

TCA-7

the next step of the cycle, the double C=C bond of Fumarate (4C) is hydrated by fumarate hydratase, where H2O has an equal chance to either of the internal C=C atoms and forms malate (4C) where C-C bond is formed again.

fumarate hydratase

TCA-7: the next step of the cycle, the double C=C bond of Fumarate (4C) is hydrated by ____, where H2O has an equal chance to either of the internal C=C atoms and forms malate (4C) where C-C bond is formed again.

TCA-8

the hydroxyl group of malate undergo the f inal oxidation in the cycle, by malate dehydrogenase.

malate dehydrogenase

TCA-8: the hydroxyl group of malate undergo the final oxidation in the cycle, by ___