Fundamentals of Metabolism - 2 Flashcards
3 Main Phases of Cellular Respiration - SIMPLIFIED
- GLYCOLYSIS (CYTOSOL)
- TCA Cycle (Mitochondria)
- OXIDATIVE PHOSPHORYLATION
Enzyme Compartmentation…
Most metabolic pathways take place…..
- Most metabolic pathways take place inSPECIFIC PARTS OF THE CELL…
- Some ENZYMES ARE INTEGRAL MEMBRANE PROTEINS.
Where are Enzymes Located?
- Enzymes (even in multi step pathways) can be located IN DIFFERENT PARTS OF ORGANELLES,
e.g., mitochondria.
Mitochondrial Membrane Characteristics ….
- Inner mitochondrial membrane;
—is NOT VERY PERMEABLE - some METABOLITES CANNOT CROSS IT - Outer membrane far LESS RESTRICTIVE, contains
—–PROTEIN BASED PORES TO ALLOW PASSAGE.
What is Glycolysis and What are its Characteristics….
- Major pathway of glucose catabolism (10 step chain)
breaks 6C glucose into 2 X 3C pyruvate. - Unique - can function AEROBICALLY AND ANAEROBICALLY ,
depending on O2 availability & mitochondria. - Thus, allows TISSUES to SURVIVE for a SHORT TIME in the ABSENCE OF of O2, e.g., skeletal muscle – sprint.
- Additionally, some CELLS LACKING MITOCHONDRIA, thus RELIANT
ON ANAEROBIC GLYCOLYSIS = which provides small amounts of usable energy (2 ATP per glucose). - Get much more ATP (15+ fold more) when O2 is
available… further catabolism to CO2 + H2O.
GLUCOSE CATABOLISM:
EXPLAIN STEP 1 …GLYCOLYSIS with OXYGEN
- Glucose
- Glycolysis = 2 ATP IS FORMED BY PHOSPHORYLATING ADP.
- 2 X Pyruvate …with O2 = More ATP
- From Glycolysis NADH formed
- NAD+ is REDUCED to NADH, is now a REDUCED ELECTRON CARRIER.
- When the Cell has oxygen, the TCA cycle is the Next step.
- Glucose (6C) ⇢ ⇢ ⇢ 2 pyruvate (3C)
- Also form NADH (e- carrier) & ATP
Glucose Catabolism:
Explain step 1 GLYCOLYSIS without oxygen…
- Glucose
- Glycolysis —-> 2 ATP
- 2 x Pyruvate
- When little or No oxygen = FERMENTATION….
- Alcoholic fermentation
pyruvate 2 x ethanol + pyruvate CO2
AND
- LACTATE FERMENTATION
PYRUVATE 2 X lactate - This allows the cell to reform NAD+ & continue to
generate some ATP.
This is anaerobic metabolism.
Glycolysis - Two Main Phases EXPLAIN
- 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
- PAYPOFF: ATP and NADH generated
Some Key Reaction Types: KINASES
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
Some Key Reaction Types = DEHYDROGENASES
Oxidation-reduction = dehydrogenases
- H3C - CH2OH —HYDROGENASE—-> H3C-COH
NAD+ –> NADH - NAD+ is reduced to NADH (gains e-)
- Substrate is oxidised (losses e-)
- FYI: reaction is catalysed by alcohol dehydrogenase!
Glyceraldehdye 3-phosphate
dehydrogenase - DEHYDROGENASE
D-glyceraldehyde 3 phosphate
—–> dehydrogenase —->
1,3-bisphosphoglycerate
** NAD+ is reduce to NADH
***
Glycolysis - cytosol, glucose (6C) is processed
into pyruvate (3C)
EXPLAIN THE PROCESS..
- The next two steps
of RESPIRATION in
mitochondrion: - PYRUVATE is OXIDATIVELY
DECARBOXYLATED to Acetyl CoA. - Then the acetyl group (2C)
enters the TCA cycle. - Conversion of pyruvate
to acetyl CoA is not
part of the TCA cycle
Acetyl Coenzyme A (AcCoA)
Pivotal molecule in metabolism…
Carbohydrates -> Glucose, Lipids -> fatty acids, Alcohol, Proteins –> AAs
then PYRUVATE
–> Acetyl-CoA
TCA cycle (expulsion of CO2)
How is Aceytl-CoA formed?
- Occurs in mitochondria.
2.oxidative decarboxylation of pyruvate to acetyl
- forming AcCoA
- 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+
Pyruvate dehydrogenase
highly-regulated enzyme
& key point of metabolic control.
Why regulate enzyme activity? = 6
- For example, to maintain appropriate ATP levels.
- Major function of CATABOLISM is to REGENERATE ATP from ADP.
- If ATP PRODUCTION LAGS behind its use, ADP
ACCUMULATES. - High levels of ADP ACTIVATE ENZYMES to
SPEED UP CATABOLISM , producing MORE ATP. - If supply of ATP EXCEEDS cellular DEMAND, the
ACCUMULATION of ATP causes ENZYME INHIBITION,
CATABOLISM SLOWS - ATP & ADP often BIND the SAME ENZYMES, INHIBITING OR ACTIVATING, DEPENDENT ON CELL’S NEEDS.
PDH Activity: Simplified Regulation
Responds to energy charge in cell
explain
a. high energy charge
b. low energy charge
what is TCA and what does it require?
- Tri-Carboxylic Acid (TCA) Cycle,
2 – requires O2 , mitochondria
- Final common pathway for oxidation of CH2O, lipids &
proteins (catabolic). - Also important in anabolic processes such as glucose synthesis.
- Therefore amphibolic
6.Multiple reactions form a cycle, regenerating oxaloacetate.
The acetyl C released as CO2
TCA Cycle & Electron Transport Chain (ETC)
- Produces reducing equivalents (NADH & FADH2).
- Electrons enter electron transport chain (ETC) —>
ATP generated (via oxidative phosphorylation).
Importance of NADH & FADH2?
- Important products of Glycolysis, PDH & TCA Cycle
= NADH & FADH2 - Process that utilises these electron carriers to
produce ATP = Oxidative Phosphorylation - Occurs via Electron Transport Chain (ETC)
- 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
- Electrons move down the ETC, enabling protons to
be pumped across the inner mitochondrial membrane, forming a concentration gradient.
explain E’ = Redox potential
- Measure of ability of one molecule to pass electrons
to another. - More negative E’ indicates stronger reductant - so more readily donates e-
- As e- pass along the chain they fall to successively lower energy levels (more +ve E’).
- NADH E’ = -0.32V
⇣
multiple electron acceptors/donors
⇣
Oxygen E’ = +0.82V - *NADH is at a higher energy level than oxygen.
What is Electron Transport Chain?
- When e- pass from a compound with more negative E’ to one of more positive E’, ENERGY is released.
- Energy is used to pump protons out of the matrix,
across the inner mitochondrial membrane & into the intermembrane space – proton gradient is generated.
Electron Transport Chain…Pumping H+ across IMM creates a proton motive force.
Pumping H+ across IMM creates a proton motive force….
- 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
- O2 is the FINAL ELECTRON ACCEPTOR of Cellular Respiration.
- O2 IS REDUCED TO WATER.
SUMMARY
- Glycolysis – cytosol (pyruvate, NADH & ATP produced)
- Next two steps of respiration - mitochondrion.
PDH & TCA cycle produce CO2, NADH & FADH2 - transfer e- - to Electron Transport Chain (ETC),
- energy used to make
ATP by Oxidative Phosphorylation
What happens during Oxidative phosporylation?
- ETC complexes pass electrons from NADH/FADH2 to O2 (to make H2O).
- Simultaneously, H+ are pumped out of matrix.
— This H+ gradient is a CHEMICAL & ELECTRICAL GRADIENT, used to
SYNTHESISE ATP - 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+
MUSCLE + ADIPOSE TISSUE + BRAIN + LIVE + RB CELLS…
ALL PART AND USE THIS SPECIAL SYSTEM
Fatty acids are considered “energy-rich” because:
B) they contain a lot of reduced C-O and C=O bonds.
