1
Q
glycolysis is simply…?
A
How to make ATP out of sugar
2
Q
The mitochondria has…?
A
The mitochondria (derived from bacteria) has two membranes and most metabolic pathways have some connection with them.
3
Q
Structure of mitochondria?
A
- They have 2 membranes (outer and inner)
- They contain Cristae (folds in membrane that increase area)
- They contain matrix (the inside of the cell) which has enzymes that make ATP using H and mtDNA which are what mitochondrial protiens are made from.
4
Q
The process of metabolism involves..?
A
The process of metabolism involves many interconnected cellular pathways to ultimately provide cells with the energy required to carry out their function.
- extremely interconnected
- KREB cycle is at the centre of it all: central idea of metabolism.
5
Q
Catabolic vs. Anabolic metabolic pathways?
A
Metabolic pathways are anabolic if they make large molecules or catabolic if they break them:
Anabolic - require energy (endergonic) DG > 0
Catabolic - release energy (exergonic) DG < 0
6
Q
Creating glucose would be?
A
Anabolic
7
Q
Breaking glucose apart would be?
A
Catabolic (energy comes from broken bond)
8
Q
How do proteins use the energy released from ATP hydrolysis?
A
It can be used to power synthetic work, concentration work, electrical work, mechanical work, bioluminescent work, and generates heat.
9
Q
Where is released energy from ATP stored?
A
Released energy from ATP is stores in the Oxygen molecule that breaks away from the phosphate.
10
Q
How do cells obtain energy?
A
Cells obtain energy by the oxidation of organic molecules
11
Q
Oxidation and reduction with respect to hydrogen transfer?
A
● Oxidation is the loss of hydrogen.
● Reduction is the gain of hydrogen.
12
Q
Oxidation and reduction with respect to oxygen transfer?
A
● Oxidation is the gain of oxygen.
● Reduction is the loss of oxygen
13
Q
Oxidation and reduction with respect to electron transfer?
A
● Oxidation is loss of electrons
● Reduction is gain of electrons
14
Q
What are NAD and FAD I relation to redox?
A
NAD and FAD are coenzymes of redox reactions and electron carriers.
15
Q
What are coenzymes?
A
Coezymes are organic molecules that bind to the active sites of certain enzymes.
16
Q
NAD and FAD during catabolic steps (breakdown)?
A
NAD and FAD accept electrons (become reduced) during catabolic steps in the breakdown of organic molecules.
17
Q
NADH and FADH2 during anabolic steps (synthesis)?
A
● NADH and FADH2 donate these electrons to some other biochemical reaction normally involved in a process that is anabolic (like the synthesis of ATP).
18
Q
Most important oxidizable substance?
A
Glucose is one of the most important oxidizable substrates in energy metabolism.
19
Q
Why is glucose so important in energy metabolism?
A
- Its oxidation is highly exergonic (DG of -686 kcal/mol for complete oxidation)
- Many polysaccharides break into glucose (starch, glycogen, cellulose)
20
Q
How do enzymes catalyze oxidation?
A
Enzymes catalyze oxidation via a series of small steps in which free energy is transferred in conveniently sized packets to carrier molecules—most often ATP and NADH.
21
Q
Glycolysis is …?
A
A metabolic pathway that entails the oxidation of glucose molecules into two pyruvate molecules.
22
Q
Phase 1 of glycolysis?
A
Preparation and cleavage:
- The six-carbon glucose molecule is phosphorylated twice by ATP and split to form two molecules of glyceraldehyde-3-phosphate. This requires input of two ATP per glucose.
23
Q
Phase 2 of glycolysis?
A
Oxidation and ATP generation:
- The two molecules of glyceraldehyde-3-phosphate are oxidized to two 3-phosphoglycerate molecules. Some of the energy from this oxidation is conserved as two ATP and two NADH molecules are produced.
24
Q
Phase 3 of glycolysis?
A
Pyruvate formation and ATP generation:
- The two 3-phosphoglycerate molecules are converted to pyruvate with accompanying synthesis of two more ATP molecules, resulting in a net gain of two ATP per glucose.
25
How many enzymatic reactions are involved in glycolysis?
Glycolysis is a 10 enzymatic reaction
process that break glucose into
pyruvate
26
Simplified phases?
Glucose → 2 Pyruvate + 2 NADH + 2 ATP
● Phase 1: Add two phosphates and cleave
● Phase 2: Oxidation and ATP
● Phase 3: Make Pyruvate and ATP
27
What are the three monosaccharides that make up disaccharides?
Disaccharides are broken into three monosaccharides Glucose, Galactose and Fructose.
28
Enzyme names for monosaccharides?
Enzyme names match substrate names sucrase for sucrase, lactase for lactose and maltase for maltose.
29
What are the functions of other monosaccharides in glycolysis?
Other monosaccharides (eg Fructose and Galactose) are converted into Glycolysis intermediates.
30
Kinases?
Enzymes that phosphorlate
31
What is pyruvate the brachpoint between?
Pyruvate is the branchpoint between aerobic and anaerobic metabolism
32
Aerobic condiotins?
In the presence of oxygen, pyruvate is converted to acetyl-CoA through oxidation and decarboxylation. Acetyl CoA then becomes substrate for Aerobic respiration, oxidizing NADH to NAD.
- USES PDH
33
Anaerobic conditions?
Oxygen is absent, pyruvateis reduced to oxidize NADH. Produces lactate.
USES LDH
34
High [O2]?
Aerobic, PDH takes pyruvate
35
Low [O2]?
Anaerobic, LDH makes lactate
36
Warburg effect on tumour cells?
Tumour cells mainly metabolise glucose to lactate independent
from intracellular oxygen levels (This is the Warburg effect)
37
Normal tissues vs low oxygen tissues - metabolism of glucose?
normal tissues (a) metabolise
glucose depending on oxygen
levels with normoxic conditions
favouring complete glucose
metabolism in the mitochondria
to maximise ATP production
(oxidative phosphorylation).
Under low oxygen levels, the
majority of glucose will be metabolised to lactate, which is
excreted from the cells, but allows sustaining a minimum level of ATP production (anaerobic glycolysis).
38
How is pyruvate transported?
A mitochondrial pyruvate carrier transports pyruvate into the mitochondria.
39
Where do glycolysis and TCA cycles occur?
● glycolysis happens in the cytoplasm
● the TCA cycle happens in the mitochondria
● Acetyl-CoA enters the TCA cycle
40
What is the role of pyruvate dehydrogenase?
Pyruvate dehydrogenase converts pyruvate into Acetyl-CoA.
- This is a very complex reaction
- Adds a CoA to pyruvate
- Removes a carbon from pyruvate
- It releases lots of energy (-33DG)
- This process involves using a coenzyme to attach the two together and create Acetyl-CoA
41
What are dehydrogenases?
Dehydrogenases are enzymes that remove a pair of hydrogen atoms from a substrate, thereby oxidizing it
42
What does pyruvate dehydrogenase look like?
Pyruvate dehydrogenase is a multi enzyme complex.
- They metabolize pyruvate
- IT its very large (100 subunits)
- Exist in multiples of 3 subunits
- Binds metabolites at E1 metabolite binding sites
43
Cofactor of pyruvate dehydrogenase?
PDH needs a vitamin B1 derivative as its cofactor.
- The E1 subunit requires thiamine pyrophosphate to bind.
- Thiamine isn't thymine
- Thiamine deficiency (vitamin B1) is linked to PDH issues
44
How does glycolysis store energy?
Glycolysis stores energy as ATP and NADH molecules.
- If high [O2], PDH takes pyruvate and makes Acetyl-CoA which is then used in the CAC cycle.
45
What is the citric acid cycle?
The citric acid cycle is also called the tricarboxylic acid cycle or the Krebs cycle.
46
What is the goal of the citric acid cycle?
The entire point of the citric acid cycle is to concentrate H ions in the mitochondrial inter membrane space (between the two membranes). This is important in the steps of making ATP.
This is done through several steps:
1. glycolysis
2. Pyruvate oxidation
3. Citric acid cycle
4. Electron transport and proton pumping
5. ATP synthesis (26-28 ATP)
47
How does Pyruvate become Acteyl-CoA?
Pyruvate Is Converted to Acetyl Coenzyme A by Oxidative
Decarboxylation.
48
Decarboxylation?
Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon
dioxide (CO2).
49
What begins the citric acid cycle?
The citric acid cycle begins with the entry of Acetate as Acetyl-CoA.
50
What is the general (very general) process of the CAC?
We begin with Oxaloacetate (4 carbons) and through a series of oxidations and decarboxylations we end up with Oxaloacetate again. This is done for every pyruvate molecules are entered (1 glucose = 2 pyruvate)
51
What do we get from CAC?
We get 3 NADH and one FADH, as well as 1 ATP molecule that is not significant.
52
Important molecules in CAC?
Pyruvate -> Acetyl-CoA
Oxaloacetate (4)
Citrate (6)
Succinate (4)
53
Succinate Deydrogenase?
Succinate dehydrogenase is the molecule that makes FADH2 by reduction of FAD. This enzyme is also a part of the electron transport chain. FADH2 is very important!
54
What are the products of the CAC cycle?
The products of the CAC cycle are CO2, ATP, NADH, and FADH2.
55
What is the overall reaction of the CAC?
Acetyl-CoA → 3 NADH + FADH2 +
ATP + 2 CO2
56
What are some significant enzymes in the CAC?
PDH (creation of acetyl-coa)
Citrate synthase (makes citrate)
Succinate dehydrogenase (membrane location)
Malate dehydrogenase (malate to oxaloacetate)
57
What is the largest enzyme in the CAC?
The largest enzyme involved with the CAC is 2-Oxoglutartate Dehydrogenase. It is very significant in comparison to other enzymes.
- Stimulates release of carbon as carbon dioxide, electrons are transferred to NADH, and the remaining part is connected to coenzyme A.
58
Succinate Dehydrogenase?
Succinate dehydrogenase is the only enzyme that is found in the membrane, and it directly links itself to the electron transport chain.
- extracts H from supinate and transfers them to FAD then other areas.
- The reason thay this happens int he mitochondria is because of this enzyme being membrane bound.
59
Oxoglutarate dehydrogenase in the CAC?
Oxoglutarate dehydrogenase is a key control point in the citric acid cycle. It is inhibited by its products, succinyl CoA and NADH. A high energy charge in the cell will also be inhibitive. ADP and calcium ions (as well as NAD) are allosteric activators of the enzyme.
- This is an extremely complicated process and requires multiple cofactors and a large enzyme.
- 3 subunits each metabolize a different step.
60
Several CAC enzymes are subject to...?
Several Citric Acid Cycle Enzymes Are
Subject to Allosteric Regulation. Allosteric regulators bind to different places in the protein - not the active site.
61
how does the Kreb cycle regulate itself?
It is able to regulate itself through negative or positive feedback.
62
What are allosteric regulators?
Allosteric regulator is a substance that binds to a site on an enzyme distinct from the active site
63
SDH is the only enzyme that..?
Succinate dehydrogenase (SDH) or respiratory complex II It is the only enzyme that participates in both the citric acid cycle and the electron transport chain.
- It is a membrane protein
- It has different domains that docks the CAC to the membrane.
64
As pyruvate is completely oxidized to CO2 in the CAC, only one ATP molecule is formed. What happens to the rest of the chemical energy in pyruvate that is released when it's oxidized?
It is stored as ATP or in the reduced forms of molecules NADH and FADH2.
ATP - long term
FADH and NAD - short term, need to be converted to ATP
65
What else does the CAC play a key role in?
The Citric Acid Cycle Also Plays a Central Role in the Catabolism of Fats and Proteins
66
How is most fat stored?
Most fat is stored as deposits of triacylglycerols, which are neutral triesters of glycerol and long-chain fatty acids
67
Catabolism of triacyglycerol?
Catabolism of triacylglycerols begins
with their hydrolysis to glycerol and
free fatty acids.
68
B oxidization?
The fatty acids are linked to coenzyme A to form fatty acyl CoAs, which are then degraded by B oxidation, a catabolic process that generates acetyl CoA and the reduced coenzymes NADH and FADH2.
- the fatty acyl CoA derivative is degraded in a series of repetitive cycles that provide NADH FADH2 and acetyl-CoA.
- The process of breaking long hydrocarbons chains produces energy/
69
Energy from amino acids?
Free amno acids can be catabolized for energy.
70
How does protein catabolism begin?
Protein catabolism begins with hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain - proteolysis. The enzymes responsible for it are called proteases.
- The proteases break the chain to get energy from it.
71
Pathways of amino acid catabolism lead to...?
All of the pathways for amino acid catabolism eventually lead to pyruvate, acetyl CoA, or a few key intermediates in the citric acid
cycle. Essentially, when proteins are broken up, their free amino acids are able to form intermediates/enzymes in the citric acid cycle.
- Conversely, one might be able to take an enzyme of the CAC and use it to produce amino acids.
72
CAC intermediates can become..?
TCA cycle intermediates can be lost to cataplerotic pathways that provide precursors for biosynthesis.
73
Cataplerotic pathways vs. anapldrotic pathways?
○ cataplerotic pathways provide
precursors for biosynthesis (take out of CAC and make amino acids, lipids and sugars)
○ anaplerotic pathways regenerate
the TCA intermediates (take amino acids, sugars, or lipids and make intermediates)
74
What is the goal of the electron transport chain?
The goal of the electron transport chain is to use NADH and FADH2 (get oxidized to give energy) to concentrate H+ protons (makes a proton gradient) in the intermembrane space (where it is used to make ATP).
75
Where does the energy for the electron transport chain come from?
The energy is provided by the oxidation of NADH into NAD. Instead of ATP, the ETC uses electrons from NADH or FADH2.
- The hydride ion is removed from NADH (to regenerate NAD+) and is converted into a proton and two electrons (H-→ H+ + 2e -).
- The two electrons power the electron transport chain
- The H becomes water
76
What does the ETC do?
The ETC converts NADH into a gradient of protons.
77
General features of the ETC?
● The electrons start with very high energy and gradually lose it as they pass along the chain.
● electrons pass sequentially from one complex to another until they are
finally transferred to oxygen.
* the two electrons are used to pump the h into the membrane.
78
The ETC requires close association of?
The ETC requires the close association of the electron carriers with protein molecules.The electron carriers are prosthetic groups.
● Prosthetic groups are large non-protein molecules embedded in the protein. They allow them to do things they couldnt do before.
● Complicated chemical structures not possible with amino acids
79
Example?
Heme is the prosthetic group in hemoglobin and is is necessary for oxygen binding
80
How does complex one work?
Complex I receives 2 electrons from NADH and passed them to CoQ.
The energy is used to pump 4 H+.
- They have plenty of different prosthetic groups
- Comfornation of complex one changes
81
What is CoQ?
Coenzyme Q (CoQ) is a lipid-like carrier (aka ubiquinone).
- Ubiquinone is named for its ubiquity in the cells.
82
How does complex 2 work?
Complex II receives 2 electrons from succinate passing them directly
to FADH2 and then into to CoQ. Does not pump H+
83
How does complex 3 work?
Complex III receives 2 electrons from CoQ and passed them to
Cytochrome C. The energy is used to pump 4 H+
84
Cytochrome C?
Cytochrome C is a small protein that serves as carrier of electrons.
- CytC moves electrons from complex 3 to 4.
- CytC is a small proteins with a heme cofactor
- Heme is the electron carrier.
85
How does complex four work?
Complex IV receives 2 electrons from Cytochrome C and passed them to
Oxygen, which is reduced to water. The energy is used to pump 2 H+
- They use the passage of electrons to change protein conformation, allowing them to pump H into the intermembrane space.
86
Why do electrons move in one direction?
Electrons move in a single direction because Redox centers (electron
carriers) are organized from low to high affinity
87
Difference of NADH and FADH2 pathways?
NADH → 1 → 3 → 4 → O2
FADH2 → 2 → 3 → 4 → O2
88
Redox centers and H pumps?
The redox centers and the H+ pumps are separated in complex I.
89
What causes Complex I to direct H+
Structural changes in Complex I direct H+ to move through translocation half-channels
● half-channels are formed by
conserved polar residues and polar
cavities containing water molecules
90
What does the ETC complexes form?
The ETC forms supramolecular assemblies or supercomplexes between all of the complexes being clustered together.
91
What does the H+ flow cause?
The H+ flow back powering the synthesis of ATP.
- The power source for ATP synthase is a difference in the concentration of H+ on opposite sides of the inner mitochondrial membrane.
- Protons move through the top of the membrane protein, and ATP synthesis occurs inside the membrane using ADP + Pi + squeezing force to make ATP.
BIOL2020
flashcards
Decks in class (25)
# Cards
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Lesson 167
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Lecture 242
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Lecture 340
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Lecture 438
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Lecture 533
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Lecture 691
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Lecture 735
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Lecture 837
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Lecture 935
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Lecture 1033
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Lecture 1146
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Lecture 1251
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Lecture 1347
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Lecture 1437
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Lecture 1543
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Lecture 1651
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Lecture 1743
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Lecture 1812
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Lecture 1925
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Lecture 2041
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Lecture 2131
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Lecture 2244
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Lecture 2330
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Lecture 2442
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Lecture 2537
