Enzymes and Metabolic Disorders Lecture Flashcards

Complete set of 81 question-and-answer flashcards reviewing enzyme basics, structure, mechanism, classification, kinetics, regulation, pharmacology, clinical pathology cases, and inborn errors of metabolism.

What is an enzyme, and how does it work?

A biological catalyst (a protein) that speeds up reactions by lowering the activation energy.

What is activation energy ($E_a$)?

The minimum energy the reactants must have to start a chemical reaction.

Do enzymes make new reactions happen?

No. They only speed up reactions that would already occur on their own.

Name the two major types of chemical reactions in the body.

Catabolic and anabolic. (Catabolic = breaking down, anabolic = building up.)

Sucrose breaking down into glucose and fructose is exergonic. Why does it still need an enzyme?

Sucrose has more potential energy than the products, but it still needs $E_a$ to get started. The enzyme lowers $E_a$, so more product forms in the same amount of time.

What reaction does carbonic anhydrase speed up, and by how much?

It speeds up $CO_2 + H_2O \rightarrow H^+ + HCO_3^-$ (bicarbonate). Without it: ~$100$ molecules/hr. With it: up to $2.16 \times 10^9$ molecules/hr (2.16 billion/hr). The reaction happens on its own, just really slowly.

What are most enzymes made of?

Globular proteins (~$60$ to $2500+$ amino acids) with a unique 3D shape that has a groove called the active site.

What is the active site of an enzyme?

The groove on the enzyme where the substrate binds. Substrate binds the active site to form the enzyme-substrate complex.

What is specificity in enzyme structure?

The active site shape fits only one substrate (or type), so each enzyme catalyzes only one reaction.

Where do enzymes work? Give 3 locations with an example of each.

1) Stay inside the cell: RNA polymerase. 2) Embedded in the plasma membrane: lactase (small intestine lining). 3) Secreted: pancreatic amylase (secreted to small intestine, digests starch). All are made by protein synthesis in cells.

What are the 4 steps of enzyme action?

1) Substrate enters the active site to form an enzyme-substrate complex; 2) Induced fit: enzyme changes shape slightly; 3) Shape change stresses the bonds, lowering $E_a$, so bonds break and new ones form; 4) Product is released, enzyme is free to repeat.

What is induced fit?

The enzyme changes shape slightly after the substrate enters, for a closer fit (like a hug).

Why does the shape change of an enzyme speed up the reaction?

It stresses the bonds in the substrate, which lowers $E_a$ so bonds break and new ones form.

Is the enzyme used up in the reaction?

No. The product is released and the enzyme is free to repeat (it is unchanged).

Give one example of an enzyme reaction that breaks down and one that builds up.

Decomposition: lactose breaks down into glucose + galactose. Synthesis: glucose forms glycogen (catalyzed by glycogen synthase).

What are cofactors?

Nonprotein 'helpers' that enzymes often need.

What are inorganic cofactors? Give an example.

Ions attached to the enzyme. Example: zinc on carbonic anhydrase. Without it, the enzyme cannot work.

What are organic cofactors (coenzymes)? Give examples.

Vitamins (B6, B12), vitamin derivatives, or modified nucleotides like $NAD^+$ (which accepts hydrogen to become NADH).

What is a ribozyme? Give an example.

An RNA molecule that acts as an enzyme. Example: ribosomal RNA helps join amino acids into proteins.

How many major enzyme classes are there? Name them.

6: oxidoreductase, transferase, hydrolase, isomerase, ligase, lyase.

What does an oxidoreductase do? Give two examples.

Transfers electrons. Examples: dehydrogenase ( NAD+ or other non-oxygen acceptor) and peroxidase (H2O2 as acceptor).

What does a transferase do? Give two examples.

Transfers a functional group. Examples: phosphorylase (transfers phosphate) and kinase (transfers phosphate, usually from ATP).

What does a hydrolase do? Give examples.

Splits a bond using water. Examples: phosphatase (removes phosphate), protease (proteins), lipase (lipids), sucrase (sucrose).

What does an isomerase do? Give an example.

Converts one isomer to another. Example: mutase, which moves atoms within a molecule.

What does a ligase do? Give an example.

Bonds two molecules together. Example: synthetase (uses ATP).

What does a lyase do? Give two examples.

Splits a bond without water. Examples: decarboxylase (releases $CO_2$) and synthase.

How are enzymes usually named?

Substrate or product name (sometimes the class) + -ase.

Which enzyme names break the '-ase' rule?

Pepsin, trypsin, and chymotrypsin (all digest protein).

How does enzyme concentration affect the reaction rate?

More enzyme results in a faster rate.

How does substrate concentration affect the reaction rate?

More substrate results in a faster rate, up to saturation. At saturation all enzymes are busy, so there is no further increase.

How does temperature affect enzyme reaction rate?

Rate rises with temperature up to the optimum (~$104^\circ\text{F}$). Normal body temp = $37^\circ\text{C}$ ($98.6^\circ\text{F}$). A low fever can help fight infection.

What happens to enzymes above ~$104^\circ\text{F}$?

Bonds weaken, enzymes denature, and rates drop sharply.

What is the optimum pH for most human enzymes, and why does pH matter?

pH 6 to 8. A change in H+ disrupts the electrostatic interactions that hold the shape, leading to denaturation.

What is the exception to the normal optimum pH, and at what pH does pepsin work?

Pepsin works at pH 2 to 4 (stomach). In the small intestine (pH 6 to 9) it is denatured and inactive.

What factors control enzyme activity?

Enzyme concentration, substrate concentration, pH, and temperature. Drugs or poisons can also act as inhibitors or activators.

Why must enzymes sometimes be turned off?

To prevent overproducing product or running out of substrate.

What is an inhibitor?

A molecule that binds an enzyme and turns it off. It can be released later.

What is a competitive inhibitor?

Resembles the substrate and binds the active site, so substrate and inhibitor compete.

How does the amount of substrate affect competitive inhibition?

More substrate results in less inhibition. Less substrate results in more inhibition.

What is a noncompetitive inhibitor?

Does not resemble the substrate. Binds somewhere other than the active site.

Does substrate concentration affect noncompetitive inhibition?

No. It is affected only by the amount of inhibitor.

What is an allosteric inhibitor?

A noncompetitive inhibitor that binds the allosteric site. The active site changes shape, so the substrate cannot bind.

How do competitive and noncompetitive inhibitors differ?

Competitive: looks like the substrate, binds the active site, more substrate overcomes it. Noncompetitive: does not look like the substrate, binds the allosteric site, not affected by substrate amount.

What is a metabolic pathway?

Many enzymes in a series. Each does one step, then releases the product, which becomes the next enzyme's substrate (e.g., glucose breakdown to Co2 and H2O).

What is a multienzyme complex?

Enzymes physically attached (noncovalent bonds) that work in sequence (e.g., pyruvate dehydrogenase).

What are the two advantages of a multienzyme complex?

1) The product goes straight to the next enzyme, so it is less likely to drift off into a different pathway; 2) One complex can be regulated instead of many separate enzymes.

What is negative feedback in a metabolic pathway?

The final product acts as an allosteric inhibitor on an enzyme early in the pathway.

Walk through negative feedback in an enzyme pathway. What is the result?

Product builds up leading to more inhibition and less product; product drops leading to inhibitor letting go and the pathway speeds up again. Result: a steady state of product.

What is phosphorylation?

Adding a phosphate (by kinases or phosphorylases).

What is dephosphorylation?

Removing a phosphate (by phosphatases).

How does phosphorylation affect enzymes?

It can turn some enzymes on and others off, depending on the enzyme.

In lactose intolerance, which enzyme is involved and what does it normally do?

Lactase, located in the small intestine membrane, breaks lactose into glucose + galactose.

What causes lactose intolerance, and who is it more common in?

A lactase deficiency or abnormal (low-functioning) lactase. It is more common in older adults (less lactase made over time), and it varies by genetics.

What are the symptoms of lactose intolerance?

Nausea, diarrhea, bloating/gas.

How does penicillin work?

Inhibits a bacterial enzyme needed to build the cell wall, which slows infection.

How does pravastatin (a statin) work?

Inhibits HMG-CoA reductase in the liver (makes cholesterol), which lowers blood cholesterol and lowers heart attack and stroke risk.

What does aspirin block?

Blocks two enzymes that cause inflammation.

How does cyanide inhibit enzymes?

Irreversible inhibition. Combines with copper and iron in the active site of an enzyme and disrupts cellular respiration.

Which enzyme does sarin inhibit?

Acetylcholinesterase.

Which enzyme does warfarin block?

Vitamin K epoxide reductase.

What do MAOIs inhibit, and what is their effect?

They inhibit the monoamine oxidase enzyme family, preventing the breakdown of monoamine neurotransmitters (e.g., dopamine and serotonin).

What is the underlying defect in Phenylketonuria (PKU), and what happens if it is untreated?

A mutation of a single amino acid in phenylalanine hydroxylase (first step in breaking down phenylalanine). Phenylalanine and related products build up leading to intellectual disability if untreated. Treatment: screening, dietary modification.

In the pathway where pyruvate forms acetyl CoA (for the Krebs cycle) and lactate: what happens if the enzyme for pyruvate to acetyl CoA is inhibited?

Pyruvate and lactate increase; acetyl CoA decreases.

In a metabolic pathway where $A \rightarrow C \rightarrow D$ and $A \rightarrow B$, what happens if the enzyme for $A \rightarrow C$ is nonfunctional?

A and B increase; C and D decrease. (A builds up, so more of it goes down the path to B.)

How does an enzyme help digest sucrose?

It breaks sucrose into glucose and fructose. Only these smaller sugars are absorbed from the small intestine into the bloodstream. Some enzyme reactions go both ways, and sometimes ATP is needed.

What is the defect, symptom, and treatment for Malignant PKU?

Defect: biopterin cofactor; Symptoms: neurological disorder; Treatment: not listed on the slide.

What is the defect, symptoms, and treatment for Type 1 tyrosinemia?

Defect: fumarylacetoacetate hydrolase; Symptoms: nerve damage, pain, liver failure; Treatment: liver transplantation; preceding enzyme inhibitor plus dietary modification.

What is the defect, symptom, and treatment for Type 2 tyrosinemia?

Defect: tyrosine aminotransferase; Symptoms: irritation to the corneas of the eyes; Treatment: diet with reduced phenylalanine and tyrosine.

What is the defect, symptoms, and treatment for Alkaptonuria?

Defect: disorder of tyrosine breakdown; Symptoms: progressive arthritis and bone disease; dark urine; Treatment: not listed on the slide.

What is the defect, symptoms, and treatment for Homocystinuria / hyperhomocysteinemia?

Defect: cystathionine-$\beta$-synthase, or methylenetetrahydrofolate reductase, or deficiencies in forming the methylcobalamin form of vitamin B12; Symptoms: hypercoagulable blood, vascular episodes, lens dislocation, long thin bones, often intellectual defects or psychiatric abnormalities; Treatment: vitamin B12, folic acid, betaine, diet limited in cysteine and methionine.

What is the defect, symptoms, and treatment for Maple syrup urine disease?

Defect: branched-chain ketoacid dehydrogenase complex; Symptoms: high branched-chain amino acids, characteristic urine odor, ketoacidosis episodes, death; Treatment: thiamine; careful control of dietary branched-chain amino acids.

What is the defect, symptoms, and treatment for Propionic acidemia?

Defect: propionyl-CoA carboxylase; Symptoms: generalized metabolic dysfunction, ketoacidosis, death; Treatment: diet with limited amounts of the amino acids that are precursors to propionyl-CoA.

What is the defect and treatment for Multiple carboxylase deficiency?

Defect: pyruvate carboxylase and 3-methylcrotonyl-CoA carboxylase; Treatment: biotin. (No symptoms listed on the slide.)

What is the defect and treatment for Methylmalonic acidemia?

Defect: methylmalonyl-CoA mutase; defects in the enzyme systems involved in vitamin B12 metabolism; Treatment: large doses of vitamin B12; diet. (No symptoms listed on the slide.)

What is the defect, symptoms, and treatment for Hyperlipidemia / hypercholesterolemia?

Defect: regulation or utilization of lipoproteins; Symptoms: cardiovascular disease; Treatment: dietary changes and drugs that inhibit fatty acid synthesis.

What is the defect, symptoms, and treatment for Fatty acid oxidation disorders?

Defect: acyl-CoA dehydrogenases (very long, long, medium, short chain) and hydroxyacyl-CoA dehydrogenases; Symptoms: low blood sugar, muscle weakness, cardiomyopathy. Treatment: avoid fasting, IV glucose, carnitine, medium chain triglycerides.

What is the defect, symptoms, and treatment for Glycogen storage diseases?

Defect: defects in glycogenolysis; Symptoms: liver enlargement or damage, muscle weakening or breakdown, kidney tubule problems, risk of brain damage; Treatment: not listed on the slide.

What is the defect, symptom, and treatment for Galactosemia?

Defect: galactose-1-phosphate uridyl transferase; Symptoms: liver failure in infancy; Treatment: newborn screening; milk avoidance.

What is the defect and symptoms for Congenital disorders of glycosylation?

Defect: enzymes that build the carbohydrate side-chains on proteins; Symptoms: quite variable; multisystem; Treatment: not listed on the slide.