Chapter 1: Enzymes and metabolism (C7613846)

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1 Enzyme structure, function

Hydrolysis (add water, defined ) breaks down molecules slowly.

“Then why doesn’t rain melt grass?” Mandy asked, “I can still see a bright green world, but of course, maybe the grass IS greener on the other side .”

“Because without an enzyme, that reaction is VERY slow.”

 Frequently asked questions Okay, so hydrolysis is where you add water. The opposite [i.e. where you take water away was called, from chemistry] is...CondensationThat makes sense, because "condensation" is where something is "condensed", is... "removed". But, is there an easy way to memorize that hydrolysis is linked with "breakdown" of molecules?When you have a long bath, your skin starts to become crinkled... The water, is breaking down your skin But as with all words in science, divide the word. "Hydro" meaning "water", and "lysis" meaning "breakdown". So the breakdown of stuff using water.But this isn't seen in reality? We water plants. They don't melt...?It occurs, but veeeeeeeeeery sloooooooooowly. That's why you need catalysts

Enzymes are catalysts of biological composition (usually protein), and can be identified by the “-asesuffix (at the end of its name). Catalysts speed chemical reactions to such a degree that without them, reactions would occur too slowly to be even relevant. Catalysts work by lowering the activation energy, which is the energy required to break the bonds within the reactants, so that the reaction can proceed. Enzymes themselves however, are not consumed by the reactions they catalyze [and hence aren’t reactants].

 Frequently asked questions What are catalysts?They speed up reactions. To the degree that without them, the reaction would occur so sloooooooooowly that it is the same as if it never happened.So catalysts are like Red Bull?Only if the recipient essentially does nothing without Red Bull.Yes, that is the case.And what's the difference between an enzyme and catalyst?Enzyme is a type of catalyst. They are catalysts made of protein.What are some examples of enzymes?Lactase. Salivary amylase. As you can see, they all end with the suffix "-ase".What is activation energy?Energy required to break bonds. When reactions occur, bonds are broken, and then re-formed. Without the breaking of the bonds, they cannot be re-formed, so no reaction occurs !So lowering this [activation energy] would cause...More reaction to occur YAY!!!!Why isn't the enzyme included as a reactant, but rather, placed above the direction arrow?Because it isn't consumed by the reaction. Nothing happens to it.So if you think about it, enzymes aren't exactly like Red Bull, because you drink Red Bull. It's consumed.It's more like the pretty girl, who makes you wanna show off  Poindexter usually doesn't have the wits to talk to her, and just looks at her... for inspiration.Right.

 Quiz #Q4950297 An enzyme is best described as what? expand

An enzyme is best described as what?

 Quiz #Q9962514 Enzymes: expand

Enzymes:

Most enzymes are larger than their substrates. Substrates are the reactants of a chemical reaction. Enzymes have an active site, which is the part of an enzyme where substrates bind. The enzyme’s active site has a shape complementary to a substrate, meaning that only a specific substrate can be catalyzed by a particular catalyst, known as [enzyme] specificity, or the lock and key model. This specificity is what distinguishes enzymes from other catalysts. Alternatively, the substrate may reshape the active site to force fitting, known as the induced fit hypothesis.

“I’ve the only key to your locked heart,” Jamie said.

 Frequently asked questions What is a substrate?Reactant of the chemical reaction. The thing, which the enzyme wants to speed up. So your Red Bull example: the substrate is, you.Why does it matter that the substrate is smaller than the enzyme?Because the substrate binds to the enzyme. Not vice versa.What is the active site?The place [on the enzyme] where the substrate/reactant, binds to the enzyme.And whether it binds or not is determined by whether the enzyme is the correct lock, for the substrate/reactant key?Correct. This is known as specificity.Forcing it to fit is known as the...Induced fit hypothesis.

Classically, the reaction speed depends on the concentration of substrate, as this will increase the amount of collision (from ), and therefore reaction. However, because of the lock and key requirement, as more substrate is added to a reaction, available enzyme active sites can be filled to saturation, such that reaction rate will no longer increase, known as saturation kinetics.

There is an optimal temperature for enzyme activity, as increasing temperature speeds up reaction, but heating too much can denature an enzyme [as it is a protein]. There is also an optimal pH for enzyme activity, with extremes again, denaturing it. For example, stomach enzyme pepsin has an optimal pH of $2$, in contrast with mouth enzyme salivary amylase which has an optimal pH of $7$.

 Frequently asked questions Increasing substrate/reactant will increase reaction rate?YesHowever, there is a saturation level?Yes. If all the active sites on the enzyme are filled, the enzyme and substrate/reactant can no longer react. So reaction rate will no longer increase, because there is now reversion to the super sloooooooooow speed.Increasing temperature will increase reaction rate?YesHowever, there is an optimal level?Yes. Heating a protein too much will denature it.There is also an optimal pH?Yes. Extreme pH causes protein to denature.

The pH at which most enzymes in the body operate best at is:

 Quiz #Q1958780 The enzyme: expand

The enzyme:

2 Enzyme control

Enzyme inhibition is the binding of a molecule to enzymes, thereby decreasing activity of the enzyme. Enzyme inhibition is used in:

• Negative feedback, where the products at the end of a reaction [chain], inhibits the function of an enzyme [required earlier in the reaction]
• Poison, which inhibit enzymes required in normal metabolism

Enzyme inhibitors work by:

• Competitive inhibition, where an inhibitor binds to the active site [of the enzyme], thereby preventing substrate from being able to bind to the [enzyme’s] active site. Note that because substrates bind and unbind from an enzyme’s active site rapidly, competitive inhibition can be overcome by increasing substrate concentration
• Irreversible inhibition, where an inhibitor will covalently bind to an [enzyme’s] active site, thereby making the binding irreversible
• Non-competitive inhibition, which changes the shape of the enzyme, thereby indirectly changing the shape of the active site too, so no substrate can bind with the enzyme’s active site at all. Note therefore, that increasing substrate concentration does not overcome non-competitive inhibition

Apart from inhibition, enzymes can be controlled by first releasing an inactive precursor enzyme known as a proenzyme (or zymogen), before becoming activated when required. Specifically, phosphorylation turns protein enzymes on, and dephosphorylation turns proteins off.

The bad boy stirs trouble, to spur others towards Christ (Hebrews 10:24)

“That passage says stir towards ‘love’?” Victoria asked.

“As Miley Cyrus said ‘GOD IS LOVE!’” Emily contended, “So spurring towards love is akin to spurring towards Christ, or at least is only done through Christ.”

“Even though Miley Cyrus then applied this to meaning God loves everyone, including homosexuals, and therefore, that homosexual marriage is alright.”

“Miley is right when she says God loves everyone, but there seems to be a hidden assumption in her logical reasoning that loving someone means condoning everything they do, which is wrong,” Mandy suggested.

 Frequently asked questions Enzyme activity can be controlled by...Two ways - a precursor enzyme, or enzyme inhibition.Enzyme inhibition can occur by...Two ways - competitive inhibition, and non-competitive inhibition.Whereas competitive inhibition can be overcome by increased substrate/reactant concentration; non-competitive inhibition cannot be. Competitive inhibition is like sitting on a seat in musical chairs, so others can't sit on it. You'll have to get off eventually, so increased substrate/reactant will eventually defeat you.Non-competitive inhibition is like smashing that chair, so no one can sit on it, ever again.What is an example of a proenzyme?Angiotensinogen, which is activated by phosphorylation, into angiotensin I. We'll get to this in the RAAS system, later on.

 Learning activity What are the two methods of enzyme control?Then, describe the two types of enzyme inhibition, and how they differ.What is the difference between phosphorylation, and dephosphorylation, and what do they do?

3 Basic metabolism

Cellular respiration is the set of metabolic reactions which releases energy. These chain of reactions include:

Step 1) Catabolism, which is the breakdown of molecules into smaller units, thereby releasing energy, for example, the breakdown of carbohydrates into its constituent glucose molecules

 Frequently asked questions So what is the relationship between catabolism and metabolism?Metabolism are reactions important for life. There are two types of metabolism - catabolism, which is the breakdown of molecules [from larger molecules]. And anabolism, which is the build up of molecules [from smaller constituents].If breaking stuff down releases energy, does building stuff up require energy?Yes.Why is catabolism used in cellular respiration? Can't you just start at glycolysis, as glucose is the body's main form of energy?Not really. Although you can often start at glucose, you may also be intaking carbohydrates [which break down into its constituent glucose molecules]. This is not even to mention, other inputs which need to be broken down, such as protein or fats.

Step 2) Glycolysis, which is the breakdown of glucose molecules into two 3-carbon pyruvate molecules in the cytosol of the cell, producing a net of $2 NADH$ and $2 ATP$. Glycolysis can occur with or without oxygen.

$\ce{Glucose + 2 NAD^{+} + 2 ADP -> 2 Pyruvate + 2NADH + 2ATP + (heat)}$

If aerobic respiration cannot proceed [such as because there is insufficient oxygen], fermentation will occur, removing one oxygen from pyruvate, and oxidizing the $\ce{NADH}$ back into $\ce{NAD+}$ thereby permitting the reaction to repeat. Lactic acid fermentation is the conversion of pyruvate into lactic acid.

$\ce{Pyruvate + NADH -> Lactic acid + NAD+}$

Some organisms such as yeast, undergo ethanol fermentation, which is the conversion of pyruvate into ethanol.

$\ce{Pyruvate + NADH -> Ethanol + CO2 + NAD+}$

Fermentation produces a net of $2 ATP$, which in addition to the $2 ATP$ produced in glycolysis, is $4 ATP$ in total. Although , $NADH$ is converted by the electron transport chain (ETC) into ATP, fermentation will convert $\ce{NADH}$ back into $\ce{NAD+}$, thereby restricting it from entering the ETC.

 Frequently asked questions Glycolysis is...The breakdown of glucose. "Glyco" meaning "glucose", and "lysis" meaning "breakdown". So the breakdown of glucose.After glycolysis, why does fermentation occur?Glycolysis [apart from the conversion of glucose into pyruvate], also converts the input $NAD^{+}$ into NADH. This thus reduces the $NAD^{+}:NADH$ ratio. However, this is a very important reaction in producing "ATP" (energy) for the body.Hence, the body needs to reverse the reduction in the $NAD^{+}:NADH$ ratio. To do this, it would like to proceed to Step 3 . However, that reaction (aerobic respiration) requires oxygen. Where there is insufficient oxygen, fermentation will occur instead.

Step 3) If aerobic respiration can proceed, the products of glycolysis are transferred to mitochondria, which require $1 ATP$ to transfer each $NADH$ across the mitochondrial membrane. As there are $2 NADH$ produced by a single glucose molecule, $1\times 2=2 ATP$ is required. Pyruvate decarboxylation is the conversion of the [3-carbon] pyruvate into the [2-carbon] acetyl-CoA, producing $1 NADH$.

$\ce{Pyruvate -> Acetyl CoA + NADH + CO2}$

 Frequently asked questions Why is it crucial that subsequent steps occur in the mitochondria?The mitochondria is called the power plant of the cell, because it's where the majority of the ATP in a cell is produced. So yes - glycolysis and fermentation can occur outside the cell, and in the absence of oxygen, but it's far less than the ATP that will be produced .

Step 4) Krebs cycle takes the 2-carbon pyruvate and adds it to the 4-carbon oxaloacetate, to produce the 6-carbon citrate. Each turn of the cycle produces one ATP, three NADH, and one FADH.

 Frequently asked questions In short, what is Krebs?It is a massive power generator. Although it seems like only 1 ATP - don't forget the 3 NADH, and 1 FADH. See from next how the ETC creates massive power with these latter two substances.

Step 5) The electron transport chain is a series of cytochromes, which are proteins embedded in the mitochondrial inner membrane. The cytochromes pass high-energy electrons from one to another, utilizing the energy of the electron to pump protons from the mitochondrial matrix into the intermembrane space, thereby leaving the intermembrane space with a low pH (acidic, since there is increased protons there now), thereby creating an electrochemical gradient [between the mitochondrial matrix and intermembrane space]. ATP synthase is an enzyme found in the inner mitochondrial membrane, which permits protons to flow back [from the intermembrane space] into the matrix, to generate ATP. The electron transport chain converts each $NADH$ into $3 ATP's$, and each $FADH$ into $2 ATP's$. The final electron acceptor is oxygen, causing oxygen to be reduced (gain of electron, discussed ) to water.

In each Krebs cycle, the equivalent $ATP$ produced by each turn of the cycle is $1+3(3)+1(2)=12 ATP$. Noting that there are two pyruvate’s [as a result of each glucose molecule entering glycolysis], so there are thus two turns of the Krebs cycle [for each glucose molecule], or $12\times 2=24 ATP$. Remember glycolysis produced $2 NADH$ and $2 ATP$, thus the equivalent ATP produced by each glucose molecule in glycolysis is $2(3)+2=8 ATP$. Remember that transporting the NADH produced by glycolysis into the mitochondria will expend $2 ATP$. Remember pyruvate decarboxylation produced $1 NADH$, and there are two pyruvate’s for each glucose molecule, thus the equivalent ATP produced by each glucose molecule in pyruvate decarboxylation, $2 \times 1(3)=6 ATP$. Therefore, the total ATP produced per single glucose molecule is $24+8-2+6=36 ATP$. Note that this is far more than the $4 ATP$ produced by fermentation. Note also that the $36$ number is the theoretical maximum, and that the actual production of ATP is may be less.

Although aerobic respiration may seem like combustion of glucose because it shares the formula $\ce{Glucose + O2 -> CO2 + H2O}$, it is distinct because combustion doesn’t occur in a series of steps.

 Frequently asked questions These numbers are tricky. So one glucose produces 2 pyruvates. And one pyruvate produces 1 acetyl CoA? So each glucose will create 2 cycles of Krebs?Yes.What is the electron transport chain (ETC)?They are pumps [in the mitochondrial inner membrane], which help convert NADH into 3 ATP's, and FADH into 2 ATP's.So each glucose produces 36 ATP through aerobic respiration?Correct.And each glucose produces 4 ATP - FAR LESS - through anaerobic respiration?Correct.The main difference between aerobic respiration and combustion is...That aerobic respiration occurs through a series of steps. Not all at once.

Fats and proteins can also enter the Krebs cycle:

• Triglycerides are broken into a glycerol backbone and 3 fatty acids. Glycerol can be converted into glucose or acetyl-CoA, which can enter glycolysis or the Krebs cycle respectively. Fatty acids can be transported into mitochondrial matrix, to cleave 2-carbonacetyl CoA’s [at a time] from the fatty acid, which can directly enter the Krebs cycle, thereby creating a lot of energy
• Proteins are broken into their constituent amino acids, with the carbon backbone becoming a source for acetyl-CoA cleaving akin to the process of fatty acids (just )

 Frequently asked questions So not only can sugar enter the Krebs cycle, but so can fats and proteins?Yes.Triglycerides/fats are made up of...A glycerol backbone, and 3 fatty acids. The glucose part can enter glycolysis. And the fatty acid part can directly enter the Krebs cycle.Proteins are made up of...Amino acids. Their carbon backbone can also directly enter the Krebs cycle.

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# Pre-med science (MED5118352)

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