Kaarten: MBP Week 1 | Quizlet

Oxido-Reductase Enzymes

Enzymen die reacties katalyseren waarin een molecuul wordt geoxideerd, terwijl een ander wordt gereduceerd. Deze enzymen worden veelal oxidase, oxigenase, dehydrogenase of reductase genoemd.

Transferase enzymes

Enzymen die een groep overzetten, zoals kinasen, die een fosfaat-groep overzetten.

Hydrolase enzymes

Enzymen die een hydrolyse-reactie uitvoeren, waarbij een groep wordt afgesplitst. Zoals proteasen, die peptide bindingen tussen aminozuren splitsen, nucleasen, die de binding tussen nucleotiden splitsen, fosfatasen, die fosfaatgroepen verwijderen, en ATPasen, die ATP hydrolyseren.

Lysase (synthase)

Enzymen die groepen verwijderen waardoor vaak een dubbele binding of een nieuwe ring-structuur wordt gevormd. Zoals decarboxylasen, die een carboxyl-groep verwijderen, adenylaat cyclase, dat ATP omzet in cyclisch-AMP, of ATP-citraat lyase, dat citraat klieft tot acetyl-CoA en oxaloacetaat

Isomerase

Enzymen die een groep binnen het molecuul verschuiven, zoals fosfoglucomutase, dat glucose-1-fosfaat omzet in glucose-6-fosfaat, of vice versa.

Ligase (synthetase)

Enzymen die twee substraten aan elkaar zetten (ligeren) ten koste van ATP- hydrolyse. Zoals pyruvaat carboxylase, dat bij pyruvaat een CO2 inbouwt ten koste van een ATP

Km

Substraat concentratie bij 1/2 Vmax. Interactie van enzym met substraat (binding)

Vmax, Kcat

Het gebonden substraat wordt omgezet (de katalyse)

Competitive inhibitors

Substrate and inhibitor bind the same substrate binding site, increased apparent Km but Vmax unchanged.

Noncompetitive inhibitors

Bind at allosteric sites (locations other than its active site), decreased apparent Vmax but Km unchanged.

Allosteric enzymes

Multidomain enzymes (a single subunit with regulatory and

catalytic domains) or multisubunit enzymes, such as dimers, trimers, and tetramers.

Allosteric inhibitors

Bind allosteric enzymes reversibly at an allosteric site (a site other than the active site) and change the enzyme conformation from a more-active, relaxed (R) state to a less-active, tense (T) state.

Allosteric inhibition can be...

noncompetitive inhibition (inhibitor binds to an allosteric site, inhibiting enzyme activity: substrate can still bind but the enzyme cannot catalyze the reaction)

competitive inhibition (inhibitor binds to an allosteric site and prevents the substrate from binding)

Suicide inhibitors

Inhibitors which participate in an intermediate step of a catalytic reaction and become converted to a more effective inhibitor

CYP enzymes

Cytochrome P450. A cytochrome is a protein that transfers electrons, using heme as its prosthetic group. The iron ion (Fe) of a cytochrome alternates between a reduced (+2) and

an oxidized (+3) state during electron transport. CYP is a family of cytochromes that absorbs light when complexed in vitro with exogenous carbon monoxide.

CYP proteins can be divided into two groups

1. those that metabolize xenobiotic (drugs, pollutants, agrochemicals)

2. those that participate in key biosynthetic pathways (biosynthesis of sterols or vitamin D)

ADME

absorption, distribution, metabolism, excretion

Absorption

The drug needs to be hydrophilic as to be soluble, but not too much to be able to cross plasma membranes. Drugs that are taken up by diffusion, have to be within the Lipinski's rules.

Distribution

The hydrophobic compounds do not dissolve in the blood and bind to proteins as piggy backs for distribution. A problem for distribution is the blood-brain barrier.

Metabolism

The combination of chemical reactions through which an organism builds up or breaks down materials

Excretion

Excretion is performed by the kidneys and liver. Kidneys absorb compounds, which they excrete in the urine. Liver transport compounds into the bile, which excretes into the stool. Some compounds are recycled after excretion by enterohepatic cycling, where the compounds is taken up into the blood from out the intestines.

Catabolism

Metabolic pathways that break down molecules, releasing energy.

Anabolism

Metabolic pathways that construct molecules, requiring energy.

ATP

(adenosine triphosphate) main energy source that cells use for most of their work

How is ATP created?

90% of the ATP is created by oxidative phosphorylation. The other 10% of ATP is formed by substrate-level phosphorylation.

Substrate-level phosphorylation

The enzyme-catalyzed formation of ATP by direct transfer of a phosphate group to ADP from an intermediate substrate in catabolism.

creatine phosphate (CP)

The storage molecule for excess ATP energy in resting muscle

adenylate kinase

2 ADP

Electron carriers

NADH and FADH2

Carbon carriers

Acetyl-CoA is an carbon carrier with an activated acetyl group

Oxidation

loss of electrons

Reduction

gain of electrons

Most important fuels of the body

Glucose and fat

Why is aldehyde dangerous for the body?

It can react with several molecules, such as copper ions, amino groups, and C% hydroxyl groups

Three stages of metabolism

1) Break down of macromolecules

2) Oxidation to ATP-producing metabolites

3) (If there is O2) Citric acid cycle and oxidative phosphorylation to form more energy

The citric acid cycle has two simpleoxidation reactions, catalyzed by __________ and _________. And two oxidative decarboxylations,catalyzed by ________ and ________.

succinate dehydrogenase, malate dehydrogenaseand

isocitrate dehydrogenase, α-ketoglutarate dehydrogenase

Acetyl CoA can be broken down into

CO2 and fat

Aerobic glycolysis

The breakdown of glucose by enzymes, releasing energy and pyruvic acid.

Three stages of glycolysis

1. energy-investment stage

2. splitting stage

3. production stage

Investment stage of glycolysis

Addition of phosphate groups from ATP with kinases (2 ATPs needed)

Activation step of glycolysis

The conversion of glucose to glucose-6-P by hexokinase (HK). This conversion traps the molecule inside of the cell, as it cannot cross the membrane anymore.

Commited step in glycolysis

G-6-P is converted to fructose-6-P by phosphoglucose isomerase and eventually to F-1,6-BP by phosphofructokinase-1. (PFK-1)

Splitting stage of glycolysis

In this stage, F-1,6-BP is split to obtain two C3 molecules by aldolase. The intermediates are called GAP and DHAP.

Production stage of glycoslysis

4 ATP and 2 NADH are formed per glucose molecule. This step is performed by pyruvate kinase

Anaerobic glycolysis

The overall process where pyruvic acid generated durring glycolysis is converted to lactic acid

Hexokinase

The enzymes that catalyzes the phosphorylation of glucose to form glucose-6-phosphate in the first step of glycolysis.

Hexokinase 1 vs Hexokinase 4

Hexokinase 1: has a low Km and can be inhibited by G-6-P, the muscle and brain express this enzyme.

Hexokinase 4 also called glucokinase and has a high Km, not inhibited by G-6-P, active in liver

Phosphofructokinase-1 (PFK-1)

In the muscle cell, PFK-1 is inhibited by ATP, a low pH, and citrate, while it is activated by AMP.

In the liver, PFK-1 is regulated by a metabolite. When there is a lot of F-6-P, it is converted by PFK-2 into F-2,6-BP. This metabolite is stimulating the activity of PFK-1.

Fructose

Only broken down in liver by fructokinase.

Why is fructose more fattening that glucose?

The most important regulated step (PFK-1) is by-passed

penthose phosphate pathway (PPP)

The PPP is used for production of NADPH and ribose-5-phosphate for RNA/DNA synthesis out of glucose. The PPP is conducted in the cytosol.

Two phases of PPP

Oxidative phase and non-oxidative phase

Oxidative phase of PPP

glucose-6-P is converted by glucose 6-phosphate dehydrogenase into 6-phosphoglucono-J-lactone. This conversion results in NADPH being formed. After this, ribose-5-P is formed. The total reaction is G-6-P+2NADP+ +H2O --> R-5-P+2NADPH+2H+ +CO2

Non-oxidative phase of PPP

Transformation of ribose-5-phosphate into 5 other molecules.

Four modes of PPP

1. Production of only ribose-5-phosphate, 2. Production of NADPH and ribose-5-phosphate, 3. Production of only NADPH, 4. Productionof NADPH and ATP

Citric acid cycle

Completes the breakdown of glucose by oxidizing a derivative of pyruvate to carbon dioxide.

Products of TCA cycle

At the end of two cycles, the products are: two GTP, six NADH, two FADH2, and four CO2.

Which enzyme links TCA tp glycolysis?

Pyruvate dehydrogenase by converting pyruvate into Acetyl-CoA (irreversible)

Which enzyme links the PPP to glycolysis?

The non-oxidative phase links PPP to glycolysis