Fundamentals of Metabolism - 2 Flashcards

1
Q

3 Main Phases of Cellular Respiration - SIMPLIFIED

A
  1. GLYCOLYSIS (CYTOSOL)
  2. TCA Cycle (Mitochondria)
  3. OXIDATIVE PHOSPHORYLATION
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2
Q

Enzyme Compartmentation…

Most metabolic pathways take place…..

A
  1. Most metabolic pathways take place inSPECIFIC PARTS OF THE CELL…
  2. Some ENZYMES ARE INTEGRAL MEMBRANE PROTEINS.
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3
Q

Where are Enzymes Located?

A
  1. Enzymes (even in multi step pathways) can be located IN DIFFERENT PARTS OF ORGANELLES,

e.g., mitochondria.

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4
Q

Mitochondrial Membrane Characteristics ….

A
  1. Inner mitochondrial membrane;
    —is NOT VERY PERMEABLE - some METABOLITES CANNOT CROSS IT
  2. Outer membrane far LESS RESTRICTIVE, contains
    —–PROTEIN BASED PORES TO ALLOW PASSAGE.
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5
Q

What is Glycolysis and What are its Characteristics….

A
  1. Major pathway of glucose catabolism (10 step chain)
    breaks 6C glucose into 2 X 3C pyruvate.
  2. Unique - can function AEROBICALLY AND ANAEROBICALLY ,
    depending on O2 availability & mitochondria.
  3. Thus, allows TISSUES to SURVIVE for a SHORT TIME in the ABSENCE OF of O2, e.g., skeletal muscle – sprint.
  4. Additionally, some CELLS LACKING MITOCHONDRIA, thus RELIANT
    ON ANAEROBIC GLYCOLYSIS = which provides small amounts of usable energy (2 ATP per glucose).
  5. Get much more ATP (15+ fold more) when O2 is
    available… further catabolism to CO2 + H2O.
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6
Q

GLUCOSE CATABOLISM:

EXPLAIN STEP 1 …GLYCOLYSIS with OXYGEN

A
  1. Glucose
  2. Glycolysis = 2 ATP IS FORMED BY PHOSPHORYLATING ADP.
  3. 2 X Pyruvate …with O2 = More ATP
  4. From Glycolysis NADH formed
  5. NAD+ is REDUCED to NADH, is now a REDUCED ELECTRON CARRIER.
  6. When the Cell has oxygen, the TCA cycle is the Next step.
  7. Glucose (6C) ⇢ ⇢ ⇢ 2 pyruvate (3C)
  8. Also form NADH (e- carrier) & ATP
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7
Q

Glucose Catabolism:
Explain step 1 GLYCOLYSIS without oxygen…

A
  1. Glucose
  2. Glycolysis —-> 2 ATP
  3. 2 x Pyruvate
  4. When little or No oxygen = FERMENTATION….
  5. Alcoholic fermentation
    pyruvate 2 x ethanol + pyruvate CO2

AND

  1. LACTATE FERMENTATION
    PYRUVATE 2 X lactate
  2. This allows the cell to reform NAD+ & continue to
    generate some ATP.

This is anaerobic metabolism.

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8
Q

Glycolysis - Two Main Phases EXPLAIN

A
  1. Begins with phosphorylation - traps glucose in cell,
    —as phosphorylated sugars can’t cross cell membranes …too polar.

THE 2 MAIN PHASES ARE:
1. PREPARATORY: input ATP

  1. PAYPOFF: ATP and NADH generated
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9
Q

Some Key Reaction Types: KINASES

A

Phosphorylation = Kinases

Hexokinase = adds phosphate to glucose
— ATP is Hydrolysed to ADP.

Glucokinase =
Glucose ——> GLUCOKINASE—> Glucose-6-phosphate.
ATP turns to ADP..

—Glucose-6P is trapped in the cell, so can be further metabolised

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10
Q

Some Key Reaction Types = DEHYDROGENASES

A

Oxidation-reduction = dehydrogenases

  1. H3C - CH2OH —HYDROGENASE—-> H3C-COH
    NAD+ –> NADH
  2. NAD+ is reduced to NADH (gains e-)
  3. Substrate is oxidised (losses e-)
  4. FYI: reaction is catalysed by alcohol dehydrogenase!
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11
Q

Glyceraldehdye 3-phosphate
dehydrogenase - DEHYDROGENASE

A

D-glyceraldehyde 3 phosphate

—–> dehydrogenase —->

1,3-bisphosphoglycerate

** NAD+ is reduce to NADH
***

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12
Q

Glycolysis - cytosol, glucose (6C) is processed
into pyruvate (3C)

EXPLAIN THE PROCESS..

A
  1. The next two steps
    of RESPIRATION in
    mitochondrion:
  2. PYRUVATE is OXIDATIVELY
    DECARBOXYLATED to Acetyl CoA.
  3. Then the acetyl group (2C)
    enters the TCA cycle.
  4. Conversion of pyruvate
    to acetyl CoA is not
    part of the TCA cycle
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13
Q

Acetyl Coenzyme A (AcCoA)

A

Pivotal molecule in metabolism…

Carbohydrates -> Glucose, Lipids -> fatty acids, Alcohol, Proteins –> AAs

then PYRUVATE
–> Acetyl-CoA

TCA cycle (expulsion of CO2)

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14
Q

How is Aceytl-CoA formed?

A
  1. Occurs in mitochondria.

2.oxidative decarboxylation of pyruvate to acetyl

  1. forming AcCoA
  2. IRREVERSIBLE route from Glycolysis to the
    TCA Cycle.

5.Catalysed by multimeric protein, PYRUVATE DEHYDROGENASE

6.Pyruvate + CoA + NAD+ —PDH —> CO2 + acetyl-CoA + NADH +H+

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15
Q

Pyruvate dehydrogenase

A

highly-regulated enzyme
& key point of metabolic control.

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16
Q

Why regulate enzyme activity? = 6

A
  1. For example, to maintain appropriate ATP levels.
  2. Major function of CATABOLISM is to REGENERATE ATP from ADP.
  3. If ATP PRODUCTION LAGS behind its use, ADP
    ACCUMULATES.
  4. High levels of ADP ACTIVATE ENZYMES to
    SPEED UP CATABOLISM , producing MORE ATP.
  5. If supply of ATP EXCEEDS cellular DEMAND, the
    ACCUMULATION of ATP causes ENZYME INHIBITION,
    CATABOLISM SLOWS
  6. ATP & ADP often BIND the SAME ENZYMES, INHIBITING OR ACTIVATING, DEPENDENT ON CELL’S NEEDS.
17
Q

PDH Activity: Simplified Regulation

A

Responds to energy charge in cell

explain

a. high energy charge

b. low energy charge

18
Q

what is TCA and what does it require?

A
  1. Tri-Carboxylic Acid (TCA) Cycle,

2 – requires O2 , mitochondria

  1. Final common pathway for oxidation of CH2O, lipids &
    proteins (catabolic).
  2. Also important in anabolic processes such as glucose synthesis.
  3. Therefore amphibolic

6.Multiple reactions form a cycle, regenerating oxaloacetate.

The acetyl C released as CO2

19
Q

TCA Cycle & Electron Transport Chain (ETC)

A
  1. Produces reducing equivalents (NADH & FADH2).
  2. Electrons enter electron transport chain (ETC) —>
    ATP generated (via oxidative phosphorylation).
20
Q

Importance of NADH & FADH2?

A
  1. Important products of Glycolysis, PDH & TCA Cycle
    = NADH & FADH2
  2. Process that utilises these electron carriers to
    produce ATP = Oxidative Phosphorylation
  3. Occurs via Electron Transport Chain (ETC)
  4. Electrons transferred from NADH & FAHD2 to O2 to
    drive the formation of ATP.

—–NADH electrons enter early in ETC ⇢ ⇢ ⇢ 3ATP
—- FADH2 electrons enter later ⇢ ⇢ 2ATP

  1. Electrons move down the ETC, enabling protons to
    be pumped across the inner mitochondrial membrane, forming a concentration gradient.
21
Q

explain E’ = Redox potential

A
  1. Measure of ability of one molecule to pass electrons
    to another.
  2. More negative E’ indicates stronger reductant - so more readily donates e-
  3. As e- pass along the chain they fall to successively lower energy levels (more +ve E’).
  4. NADH E’ = -0.32V

    multiple electron acceptors/donors

    Oxygen E’ = +0.82V
  5. *NADH is at a higher energy level than oxygen.
22
Q

What is Electron Transport Chain?

A
  1. When e- pass from a compound with more negative E’ to one of more positive E’, ENERGY is released.
  2. Energy is used to pump protons out of the matrix,
    across the inner mitochondrial membrane & into the intermembrane space – proton gradient is generated.
23
Q

Electron Transport Chain…Pumping H+ across IMM creates a proton motive force.

A

Pumping H+ across IMM creates a proton motive force….

  1. Like a battery – energy used to drive energy-requiring reactions,

e.g., ATP from Pi & ADP. This requires O2 &
thus = OXIDATIVE PHOSPHORYLATION and is CATALYSED by ATP SYNTHASE

  1. O2 is the FINAL ELECTRON ACCEPTOR of Cellular Respiration.
    - O2 IS REDUCED TO WATER.
24
Q

SUMMARY

A
  1. Glycolysis – cytosol (pyruvate, NADH & ATP produced)
  2. Next two steps of respiration - mitochondrion.
    PDH & TCA cycle produce CO2, NADH & FADH2 - transfer e-
  3. to Electron Transport Chain (ETC),
    - energy used to make
    ATP by Oxidative Phosphorylation
24
Q

What happens during Oxidative phosporylation?

A
  1. ETC complexes pass electrons from NADH/FADH2 to O2 (to make H2O).
  2. Simultaneously, H+ are pumped out of matrix.
    — This H+ gradient is a CHEMICAL & ELECTRICAL GRADIENT, used to
    SYNTHESISE ATP
  3. REDOX POTENTIAL BECOMING MORE POSITIVE ———–>

Chemical potential matrix alkaline + Electrical potential matrix negative = ATP synthesis driven by proton-motive force.

Note: we are NOT COUNTING NADH, ATP or H+

25
Q

MUSCLE + ADIPOSE TISSUE + BRAIN + LIVE + RB CELLS…

A

ALL PART AND USE THIS SPECIAL SYSTEM

26
Q

Fatty acids are considered “energy-rich” because:

A

B) they contain a lot of reduced C-O and C=O bonds.