150921-3 Overview of metabolic pathways

Which steps in pathways are usually regulated, and why?

(1) Committed steps- pathways are normally regulated by regulating the rate-limiting, or committed, step. This step is usually irreversible with a very large delta G. The enzyme catalyzing the rxn at this step is usually highly regulated, to prevent the synthesis of unneeded metabolites. (2) Branch points of pathways- branch points are ofen regulated, to prevent the synthesis of unneeded metabolites.

Describe the concept of interconnection of metabolic pathways and the potential impact on the effects of genetic deficiencies.

-So metabolic pathways are interconnected -Shit gone wrong in one pathway can **** shit up in a different pathway W/ regard to genetic deficiencies and rugs: -If the pancreas is unable to make insulin, glucose does not get stored as glycogen (anabolism), which means you have no sugar storage for catabolism

How does substrate concentration regulate enzymes?

A build up of substrate can drive a rxn forward; regulation typically happens in the time frame of minutes.

What is an oxidation-reduction reaction?

A rxn that involves electron transfer.

A) What is an irreversible metabolic pathway? B) What is the point of having an irreversible pathway?

A) -It's a metabolic pathway that is...irreversible -Note that individual steps of the pathway can be reversed (most are) -The pathway itself, h/e, has one step with a large, negative delta G, making it difficult to reverse B) -If the rxn sequence for anabolic and catabolic pathways were identical, their simultaneous operation would be wasteful/they could not be separately regulated TAKE HOME: anabolic and catabolic pathways have steps that use a lot of the same enzymes, but at least one of the steps will use different regulatory enzymes

Describe the following type of rxn: the addition or removal of functional groups

Addition of functional groups to double bonds or their removal to form double bonds

What does an allosteric activator do to Vmax and the Km? What does an allosteric inhibitor do?

Allosteric activator- Vmax remains unchanged but can be attained more quickly; thus, the apparent Km (Kapp) is decreased (it shifts the S curve to the left). Allosteric inhibitor- does the reverse

Distinguish b/w catabolic and anabolic pathways; compare and contrast major characteristics of these pathways.

Catabolism: -capture chemical energy as ATP -convert molecules in diet and stored nutrients into building blocks -convergent -releases energy -breaks shit down Anabolism: -small molecules combined to form complex molecules -divergent -requires energy -builds shit up

Describe the following type of rxn: hydrolytic

Cleavage of bonds by the addition of water

In the context of metabolic pathways, what is the difference between convergence and divergence?

Convergence: -lot's of shit can form the same thing (e.g., lipids, carbs, proteins can all lead to acetyl-Coa) Divergence: -one thing can form lot's of different shit (e.g., acetyl CoA can be used in TCA cyle, ketone bodies, fatty acid synthesis)

What is energy charge? What does energy charge do to metabolic pathways?

Energy charge is a communication of how much ATP is available/how much energy a cell has. Generally, less ATP translates to lower energy charge, and more ATP translates to higher energy charge. Some important points: -ATP has two high energy bonds, and ADP has one -Energy charge ranges from 0 (all AMP) to 1 (all ATP) -Catabolic pathways (i.e., ATP generating pathways) are inhibited by high energy charge -Anabolic pathways (i.e., ATP utilizing pathways) are activated by high energy charge -Energy charge is buffered, usualy from around 0.8 to 0.95 for most cells

What is Nicotinate (niacin)?

It's a vitamin precursor for the carrier molecules NADH and NADPH, which carry electrons.

Describe the following type of rxn: ligation requiring ATP cleavage

Formation of covalent bonds (i.e., carbon-carbon bonds)

What is thiamine (vitamin B1)?

It's a vitamin precursor for thiamine pyrophosphate, which carries the group aldehyde.

How does induction change the available protein concentration?

Induction = increased transcription/translation.

What is the Km?

It's 1/2 of Vmax. It is a constant that is a rough measure of the affinity of an enzyme for its substrate. A low Km corresponds to a high affinity.

What is an allosteric activator?

It's a small molecule that binds to an enzyme at a site OTHER THAN the active site, thereby enhancing substrate binding

What is an allosteric inhibitor?

It's a small molecule that binds to an enzyme at a site other than the active site, thereby reducing substrate binding

What is pantothenate?

It's a vitamin precursor for Coenzyme A, which carries an acyl group.

What is biotin?

It's a vitamin precursor for the carrier molecule biotin, which carries carbon dioxide.

What is folate?

It's a vitamin precursor for the carrier molecule tetrahydrofolate, which carries one-carbon units.

What is riboflavin (vitamin B2)?

It's a vitamin precursor for the carrier molecules FADH2 and FMNH2, which carry electrons.

Describe the relevance of vitamins to carriers of chemical groups in metabolic pathways. Provide two examples.

Many carrier molecules, which in this case function as co-enzymes, are made from vitamins. Accordingly, vitamin deficiency leads to impaired enzymatic activity in which the carrier molecules [made from vitamins] are used.

What is the "committed" step in a metabolic pathway?

Most of the steps in a metabolic pathway are reversable; h/e, one of the steps [typically earlier in the pathway] will have an irreversible rxn that commits the pathway to proceeding. Note that this is usually the rate-limiting step in the pathway.

Do allosteric regulators change the reaction equilibrium?

No.

What is sequestration?

Process of binding of either binding an enzyme with another protein to inactivate it, or physically sequestering it

Describe the following type of rxn: isomerization

Rearrangement of atoms to form isomers

How does covalent modification regulate enzymatic activity? Provide three examples.

Regulation typically occurs on a time scale of minutes to hours. Important examples include: (1) Pyruvate kinase: active when un-phosphorylated (pyruvate kinase a); inactive when phosporylated (pyruvate kinase b). (2) cAMP: regulates phosphorylation of many proteins by regulating PKA activity; binds to regulatory subunits of PKA, which lowers their affinity for catalytic subunits. This frees catalytic subunits and allows them to be active. (3) PKA: phosphorylates pyruvate kinase, which inactivates it.

How does repression change the available protein concentration?

Repression = decreased transcription/translation

What regulates metabolic pathways?

The following regulate metabolic pathways (see other note cards for more detailed) (1) The energy charge/the amount of ATP or energy a cell has (2) Feedback inhibition (3) Substrate concentrations (4) Product inhibition (5) Allosteric regulation (5) Covalent modification (e.g. phosphorylation) Note that the rate-limiting step is usually tightly regulated

What is Vmax?

The point at which every enzyme has found a substrate (i.e., the reaction cannot go any faster); it is dependent on the amount of enzyme present.

Describe the concept of "mass action"

The rate of a rxn is proportional to the product of the masses of the reactants (the more product that is formed, the less reactant is left)

Describe the following type of rxn: group transfer

Transfer of a functional group from one molecule to another

Draw a general reaction curve; label the substrate concentration, the appropriate y-axis, and draw s-curves for when an allosteric activator or inhibitor are present.

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