Lecture 7 - Exam 1

Question 1

What is metabolism?

Answer 1

The sum of the chemical reactions that occur in a cell, tissue or the body - built by pathways of enzymes converting substrates.

Question 2

What is intermediary metabolism?

Answer 2

Generation of energy from fuel molecules to feed all cells of the body - catabolism and anabolism

Question 3

What is catabolism and anabolism?

Answer 3

Break down fuel, oxidative degradation of complex molecules to simpler molecules, exergonic - energy released in reduced coenzymes NADH and FADH that carry energy forward to form ATP

Question 4

What is a special pathway?

Answer 4

Synthesize and break down biomolecules necessary for normal function of the body

Question 5

What is anabolism?

Answer 5

Production of fuel molecules - simple precursors assemble to form varied and complex biomolecules by covalent bonding and endergonic input of ATP

Question 6

What is free energy? and what are their values?

Answer 6

Energy available for useful work - deltaG = 0 at equilibrium - negative if exergonic reaction and gives energy off, positive if endergonic reaction and energy from other source is needed - energy changes in linked pathways are additive

Question 7

What is the stepwise degradation of nutrient molecules?

Answer 7

GI track takes up and digest nutrient macromolecules (proteins –> amino acids, polysaccharides –> monosaccharides, lipids –> glycerol and fatty acids), then within the cells building blocks are further degraded to yield a limited set of metabolic intermediates (acetyl CoA), and then in the mitochondria energy is generated from the intermediates (ATP)

Question 8

Where does digestion and absorption of food take place and what are the important players? where does the most digestion and absorption take place?

Answer 8

GI tract - specialized glands and surface epithelia - the small intestine

Question 9

Where do nutrient molecules go after digestion?

Answer 9

Enter the hepatic portal vein and travel to the liver and then to blood for rest of body. Fats bypass the liver and are taken up by the lymphatic circulation and delivered to bloodstream. Lipids need lipoprotein vehicles for transportation

Question 10

How are proteins degraded? What are the phases?

Answer 10

Endo and exopeptidases - stomach contains HCl and pepsin protease to cleave large peptide products that stimulate the release of CCK to initiate the pancreatic phase. In the pancreas bicarbonate and hydrolytic enzymes like trypsin are present for digestion. The epithelial cells have endo and aminopeptidase activities to degrade the peptides to amino acids which are absorbed by transport systems.

Question 11

How are carbohydrates digested?

Answer 11

Monosaccharides are absorbed in the intestinal cells, but disaccharides are digested to monosaccharides by intestinal surface enzymes and poly must be degraded to smaller building blocks. The mouth degrades by alpha amylase, also secreted by the pancrease. Further digestion occurs on surface of intestinal cells by alpha-glucosidase and oligosaccharides not hydrolyzed this way reach the lower ileum where bacteria digest sugars.

Question 12

How is fat (triglycerides) digested?

Answer 12

Starts in stomach by lipases and then the pancreas contains lipid esterase and phospholipase A2 and pancreatic lipase which anchors to the fat droplets by colipase and cleaves two fatty acids. Fats can’t be absorbed by mucosal cells unless they interact with bile salts which are produced in the liver and release by the gall bladder which act as a detergent to make soluble micelles that can interact with enterocytes. Chylomicrons deliver everything to the lymphatic system.

Question 13

What energetic pathway is occurring in the cytosol? and what kind of pathway is it?

Answer 13

Glycolysis and it is an anaerobic process - the conversion of glucose to pyruvate

Question 14

Where are the majority of the energy producing reaction located and what do they require?

Answer 14

Located in mitochondria and require oxygen - inner membrane contains most of the electron transport and oxidative phosphorylation enzymes, dehydrogenases and transport systems.

Question 15

What helps molecules through the semi-permeable inner mitochondrial membrane?

Answer 15

Transporters that exchange ATP with ADP and Pi and substrate shuttles like the malate-aspartate and alpha-glycerol phsophate shuttle to move reducing equivalents across membrane for energy generation

Question 16

Where in the mitochondria are the major energy generating reactions occurring?

Answer 16

Mitosol for PDH, fatty acid beta oxidation, krebs cycle but terminal oxidation occurs on the inner membrane

Question 17

Cells with mitochondria and good oxygenation have the possibility to utilize what to generate energy?

Answer 17

glucose (glycolysis), fatty acids (PDH) and amino acids (TCA/Krebs)

Question 18

How do fatty acids enter energy metabolism pathways?

Answer 18

Triglycerides are made up of fatty acids and glycerol. Glycerol converts to pyruvate which goes to the mitochondrium and fatty acids go directly to the mitochondrium and then to beta oxidation

Question 19

How do amino acids enter energy metabolism pathways?

Answer 19

Eliminated and can go to mitochondrium to enter TCA as intermediates then terminal oxidation or they can be turned to AcCoA to enter TCA then terminal oxidation or be turned to pyruvate to go to mictochondrium

Question 20

How does glucose enter energy metabolism pathways?

Answer 20

Glucose undergoes glycolysis in the cytosol and then converts to pyruvate and goes to mitochondria to produce AcCoa and enter the Krebs cycle/TCA and then undergo terminal oxidation

Question 21

What turns pyruvate into AcCoA?

Answer 21

The pyruvate dehydrogenase complex (PDH)

Question 22

What are sources of pyruvate?

Answer 22

Glucose and some amino acids

Question 23

What is pyruvate converted into?

Answer 23

AcCoA under aerobic conditions by PDH - or reduced to lactate under glycolysis anaerobic conditions - also can be transaminated to alanine for protein synthesis or can be carboxylated to oxaloacetate in gluconeogenesis

Question 24

What is the reaction that takes place in the PDH complex?

Answer 24

Pyruvate + NAD+ + CoA –> Acetyl-CoA + CO2 + NADH + H

Occurs in mitochondrial matrix and is irreversible and exergonic

Question 25

What is the molecular mechanism of PDH?

Answer 25

Pyruvate is converted to the enolic form of acetyl group by pyruvate dehydrogenase, then it is converted to AcCoA by Dihydrolipoyl transacetylase and lipoic acid and then goes to the TCA cycle. Dihydrolipoyl dehydrogenase and FAD then reconstruct lipoic acid from E2 and then NAD reconstructs FAD to produce more NADH for terminal oxidation

Question 26

How is pyruvate dehydrogenase regulated?

Answer 26

Acetyl CoA and NADH - the product inhibit the complex by feed-back inhibition - or it the complex can become inactive in its phosphorylated form produced by a kinase stimulated by ATP, AcetylCoA and NADH which is inhibited by pyruvate

Question 27

What happens if someone is deficient in pyruvate dehydrogenase? and what can sometimes help?

Answer 27

They have elevated lactate and pyruvate levels which produces chronic lactic acidosis - neurological defects and someones death. A ketoogenic diet where carbs are minimized can sometimes help

Question 28

What are sources of acetyl CoA?

Answer 28

PDH, some amino acids, beta oxidation of fatty acids

Question 29

What is the fate of acetyl CoA?

Answer 29

Oxidation in the TCA cycle for energy production, conversion to ketone bodies in the liver, biosynthesis of sterols and long chain fatty acids in the cytosol

Question 30

What are other names for the TCA cycle?

Answer 30

Krebs and citric acid

Question 31

What is the end result of the TCA cycle?

Answer 31

Acetyl CoA is completely oxidized to be utilized for energy and carbon dioxide and reduced cofactors are produced to go to the electron transfer system

Question 32

What is the mechanism of TCA cycle?

Answer 32

Acetyl CoA condensates with oxaloacetate and is processed with oxidative cleave reactions which forms CO2, regenerates oxaloacetate and produces 3 NADH, a FADH2 and a GTP - utilizes dehydrogenase enzymes which produces reduces coenzymes that are the most important regulatory enzymes of the cycle

Question 33

What are the enzymes used in the TCA cycle?

Answer 33

Dehydrogenases: Citrate synthase when AcCoA enters, Isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthase, succinate dehydrogenase, and malate dehydrogenase

Question 34

What are the energetics of the TCA cycle?

Answer 34

3 NADH, 1 FADH, 1 GTP per turn of the TCA Oxidation of each NADH yields 3 ATP, FADH2 yields 2 ATP, and GTP is converted to 1 ATP which gives 3x3 + 1x2 + 1 = 12 ATPs for each turn

Question 35

What regulates the TCA?

Answer 35

The supply of AcCoA, PDH regulation, mitochondrial terminal oxidation that produces NAD+ and FAD, availability of ADP + Pi and oxygen to produce ATP, key enzyme regulators are citrate synthase, isocitrate dehydrogenase, and alphaketoglutarate dehydrogenase

Question 36

What are TCA cycle deficiencies/disease?

Answer 36

Deficiencies of the enzymes of TCA is rare, but fumarase deficiency has been recording a couple of times which resulted in neurological impairment, encephalomyopathy and dystonia. Arsenic poisoining affects enzymes that use lipoic acid as a cofactor (PDH or alphaketoglutarate DH). Pyruvate dehydrogenase deficiency is a cause of congenital lactic acidosis.

Question 37

What are anaplerotic reactions? And which is most important?

Answer 37

Replenish intermediates of TCA - because intermediates are normally removed for biosynthetic purposes Most important is pyruvate carboxylase which turns pyruvate into oxaloacetate

Question 38

What is the purpose of terminal oxidation?

Answer 38

To carry electrons and protons from reduced coenzymes (NADH and FADH) to oxygen = electron transport Convert reducing power to ATP energy = oxidative phosphorylation

Question 39

Where does terminal oxidation occur?

Answer 39

Mitochondrial inner membrane

Question 40

Where do NADH and FADH come from?

Answer 40

NADH produce in glycolysis and transported to mitochondria by shuttle, PDH, TCA, fatty acid beta oxidation FADH produced in TCA and fatty acid beta oxidation

Question 41

What is the mechanism of the electron transport system?

Answer 41

The ETC oxidizes the reduced cofactors stepwise by transferring electrons in a series of steps to oxygen - (the terminal electron acceptor) - potential differences between redox pairs represent free energy changes that is used to synthesize ATP molecules when protons are removed and pumped across the membranes to create the electrochemical gradient

Question 42

What are the components/complexes of the electron transport chain and the mechanism by which they use them?

Answer 42

Coenzyme Q and cytochrome c and 4 large multisubunit enzyme complexes with redox system Complex I - NADH enters - electrons and protons transferred to coenzyme Q Complex II - FADH enters and transfers electrons and protons to conenzyme Q (succinate dehydrogenase) Coenzyme Q: transfers electrons to Complex III Complex III: transfers electrons to cytochrome c Cytochrome c: transports electrons to complex IV Complex IV: transfers electrons to oxygen

Question 43

What does poison do to the electron transport chain?

Answer 43

``` Inhibits the complexes - Rotenone, amytal at Complex I Antimycin A at Complex III Cyanide, azide, and carbon monoxyde at terminal step in IV Oligomycin - stops ATP synthesis ```

Question 44

At which points are protons ejected from the electron transport chain?

Answer 44

At complexes I, III, IV and they are sent out of the mitochondrial matrix into the intramembrane space

Question 45

How many ATPs are generate for each FADH and NADH?

Answer 45

2 ATPs for FADH and 3 ATPs for NADH

Question 46

How is the electrochemical gradient established and dissipated in electron transport chain?

Answer 46

Protons are pumped from the mitosol to the intermembrane space = gradient established DIssipation is coupled to the synthesis of ATP by the mitochondrial F1F0 ATPase (located on inner membrane) which allows the protons to move back into the mitosol through it's channel