Download An overview of Metabolism - Harford Community College

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An overview of Metabolism
Bio 099
December 8, 2007
Metabolism
• Metabolism is all the chemical reactions
that occur in a living organism.
Catabolism
• Catabolism is the breakdown or digestion
of organic molecules.
Catabolic reactions
release energy in the
form of ATP, which the
cell can then use for its
various functions.
What molecules does the cell
break down for energy?
• Usually fats and
carbohydrates are
the fuel of choice
– Triglycerides =
• fatty acids +
glycerol
– Glycogen =
• monosaccharides
Glycogen
– most abundant storage of carbohydrate
– a branched chain of glucose molecules
Triglycerides
– most abundant storage of lipids
– primarily of fatty acids
Proteins
– most abundant organic components in body
– perform many vital cellular functions
Metabolism Handout
Tools for making ATP
• To survive cells need to make ATP.
• For ATP synthesis the following are
required:
– oxygen
Tools for making ATP
• To survive cells need to make ATP.
• For ATP synthesis the following are
required:
– oxygen
– nutrients/vitamins
Tools for making ATP
• To survive cells need to make ATP.
• For ATP synthesis the following are
required:
– oxygen
– nutrients/vitamins
– mitochondria
Tools for making ATP
• To survive cells need to make ATP.
• For ATP synthesis the following are
required:
– oxygen
– nutrients/vitamins
– mitochondria
– enzymes
Why are catabolic reactions
necessary for the cell?
• To release energy for anabolic reactions!
Anabolism
• Anabolism is the production of new
organic molecules using cellular energy
(ATP).
For example:
Proteins are produced through
an anabolic reaction that uses
ATP to form polypeptide bonds
between amino acids.
Why is anabolism necessary?
1. Metabolic Turnover: The cell needs energy to
periodically replace its components.
2. Growth and Division: In order to grow and
divide a cell needs energy.
3. Special Processes: Depending on the specific
cell type, various functions require energy.
•
For example: muscle cell contraction requires energy.
4. Nutrient Pool: A cell keeps a reserve storage
of nutrients, just in case…
Catabolism:
Aerobic Cellular Respiration
Aerobic Cellular Respiration:
generating ATP for the cell
• Glycolysis
• Krebs cycle (TCA)
• Electron transport
chain
Aerobic Cellular Respiration
• Glycolysis
• Krebs cycle (TCA)
• Electron transport
chain
happens only in
the presence of
oxygen
aerobic: requires or takes place in
the presence of oxygen
Mechanisms of ATP synthesis
1. substrate-level phosphorylation
occurs during glycolysis and Kreb’s cycle
ADP + P  ATP
2. oxidative phosphorylation
occurs during the electron transport chain
formation of a proton (H+) gradient across the inner mitochondrial
membrane provides potential energy to make ATP
Oxidation-reduction (redox) reactions
are important in metabolism
• Oxidation: a molecule
is oxidized when it
loses electrons.
• Reduction: a
molecule is reduced
when it gains
electrons.
During metabolism enzymes catalyze these reactions
Example of a redox reaction:
NAD+
• Nicotinamide
adenine dinucleotide
(NAD+) is a
coenzyme that
carries electrons to
be used in the
electron transport
chain.
• NAD+ is made from
the vitamin niacin.
Example of a redox reaction:
FAD+
• flavin adenine
dinucleotide (FAD) is a
coenzyme that carries
electrons to be used in
the electron transport
chain.
• FAD contains riboflavin
(vitamin B2).
Carbohydrate Catabolism
• generates ATP by breaking down sugar
C6H12O6 + 6O2 6H2O + 6CO2 = 36 ATP + heat
1 molecule of glucose nets 36 molecules of ATP
Glucose must first get into the cell
• insulin binds to its receptor to tell the cell glucose is
coming and to add glucose transporter proteins to the
membrane.
• glucose is transported into the cell through facilitated
diffusion
Carbohydrate Metabolism
• Glycolysis: always
happens first.
Glycolysis
STEP 1.
Hexokinase phosphorylates glucose
creating glucose-6-phosphate
uses 1 ATP molecule
traps glucose molecule within cell
Glycolysis
STEP 2.
Phosphoglucoisomerase transforms
glucose-6-phosphate to fructose6-phophate
Glycolysis
STEP 3.
Phosphofructokinase (PFK) adds a
phosphate to fructose-6-phophate
making it Fructose 1, 6 bisphosphate.
This reaction requires 1 ATP.
Glycolysis
STEP 4.
An enzyme splits Fructose 1, 6
bisphosphate into 2
glyceraldehyde-3-phosphates
molecules.
Glycolysis
STEP 5.
Each glyceraldehyde3-phosphate is
oxidized to 1,3bisphosphoglycerate
.
At the same time
NAD+ is reduced to
NADH.
NAD+ also donates a
phosphate group in
the reaction
Glycolysis
STEP 6.
Each 1,3bisphosphoglycerate is
striped of its phosphate
groups making 3Phosphoglycerate.
The phosphates are used
to generate ATP from
ADP (2 total)
Glycolysis
STEP 7&8.
2 more enzymatic
reactions form
phosphoenolypyruvate
(PEP).
Glycolysis
STEP 9.
PEP is converted to
pyruvate generating ATP
Glycolysis
Each Glucose
makes 2
molecules of
glyceraldehyde
phosphate so
from that point
on, multiply
everything by 2:
= 2 NADH
= 4 ATP
Glycolysis: Take home message
1. ATP is used in 2
reactions at the
beginning of
glycolysis:
Glycolysis: Take home message
1. ATP is used in 2
reactions at the
beginning of
glycolysis:
1. to keep glucose in the cell
2. to make the molecule that
is then broken in half
Glycolysis: Take home message
1. ATP is used in 2
reactions at the
beginning of
glycolysis:
1. to keep glucose in the cell
2. to make the molecule that
is then broken in half
2. 4 ATP and 2 NADH are
generated in the last
half of glycolysis,
Glycolysis: Take home message
1. ATP is used in 2
reactions at the
beginning of
glycolysis:
1. to keep glucose in the cell
2. to make the molecule that
is then broken in half
2. 4 ATP and 2 NADH are
generated in the last
half of glycolysis
3. 2 pyruvate molecules
are generated from
glycolysis.
Carbohydrate Metabolism
• Glycolysis
• Pyruvic acid transition
The fate of pyruvic acid
• In the absence of oxygen (anaerobic)
• The Electron Transport Chain
(ETC) cannot run because O2 is
the final electron acceptor
• Because NADH2 cannot unload
its H ions in the ETC it returns
them to pyruvic acid forming
lactate
• This often happens in the
muscle cells during exercise
The fate of pyruvic acid
• By the way…
this is also how we make alcohol from
sugar: fermentation
The fate of pyruvic acid
• In the presence of oxygen (aerobic)
First, Pyruvic acid will
enter the mitochondria
where it is converted to
acetyl CoA:
The fate of pyruvic acid
• In the presence of oxygen (aerobic)
First, Pyruvic acid will
enter the mitochondria
where it is converted to
acetyl CoA:
1. CO2 is removed
2. H ions leave and
reduce NAD+ to
NADH2
3. coenzyme A is
added giving
acetyl CoA
The fate of pyruvic acid
• In the presence of oxygen (aerobic)
First, Pyruvic acid will
enter the mitochondria
where it is converted to
acetyl CoA:
1. CO2 is removed
2. H ions leave and
reduce NAD+ to
NADH2
3. coenzyme A is
added giving
acetyl CoA
Next, Acetyl CoA enters the
Krebs Cycle and continues
aerobic cellular respiration.
Carbohydrate Metabolism
• Glycolysis
• Pyruvic acid transition
• Kreb’s cycle
Kreb’s Cycle (TCA, citric)
• Acetyl CoA combines with
oxaloacetic acid to form citric
acid
Kreb’s Cycle (TCA, citric)
• Acetyl CoA combines with
oxaloacetic acid to form citric
acid
• as the cycle continues
carbons are removed,
forming CO2 and NAD/FAD
are reduced to NADH/FADH
(electron carriers)
Kreb’s Cycle (TCA, citric)
• Acetyl CoA combines with
oxaloacetic acid to form citric
acid
• as the cycle continues
carbons are removed,
forming CO2 and NAD/FAD
are reduced to NADH/FADH
(coenzymes and electron
carriers)
• 1 ATP molecule is made via
substrate-level
phosphorylation
The Krebs Cycle
Overall Reactants
Overall Products
•
•
•
•
•
•
•
•
•
Acetyl-CoA
3 NAD+
FAD
ADP and Pi
Coenzyme A
2 CO2
3 NADH
FADH2
ATP
Remember: 1 glucose molecule will give
double of every reactant and product!
What do you get when 1 glucose molecule is
broken down via aerobic respiration?
• Glycolysis:
– 2 ATP via substrate-level phosphorylation
– 2 NADH2
• Transition Reaction (pyruvate to acetyl CoA):
– 2 NADH2
• Krebs Cycle:
– 6 NADH2
– 2 FADH2
– 2 ATP
36 Total
ATP
Metabolism Handout:
• note that lipid and
protein break-down
also form molecules
that enter the Kreb’s
cycle.
Electron Transport Chain (ETC)
• Oxygen must be present!
• Finally we will see the fate of the coenzymes (NADH,
FADH2).
the fate of NADH2 and FADH
• NADH and FADH
drop off H ions (and
e-) at the ETC in the
mitochondria.
Electron shuttling
• e- are shuttled
through a sequence
of membrane proteins
(electron carriers).
H+ pumping
• this provides energy to
pump H ions against
their concentration
gradient
inner membrane
matrix
intermembrane
space
Electron carriers and H+ pumps
• Two types of proteins in the
inner mitochondrial
membrane shuttle e- and/or
pump H+.
Electron carriers and H+ pumps
• Two types of proteins in the
inner mitochondrial
membrane shuttle e- and/or
pump H+.
– complexes I-IV
Cytochromes
• Two types of proteins in the
inner mitochondrial
membrane shuttle e- and/or
pump H+.
– complexes I-IV
– cytochromes
• Cytochromes are
proteins with heme
groups that require Fe,
S and Cu.
Electron carriers and H+ pumps
• Two types of proteins in the
inner mitochondrial
membrane shuttle e- and/or
pump H+.
– complexes I-IV
– cytochromes
• Cytochromes are
proteins with heme
groups that require Fe,
S and Cu.
Electron carriers and H+ pumps
• Two types of proteins in the
inner mitochondrial
membrane shuttle e- and/or
pump H+.
– complexes I-IV
– cytochromes
• Cytochromes are
proteins with heme
groups that require Fe,
S and Cu.
• Coenzyme Q is not a
protein, but still carries e-.
Oxidative Phosphorylation:
ADP  ATP
• The H+ gradient creates
energy to power the ATP
synthase complex.
Oxidative Phosphorylation:
ADP  ATP
• The H+ gradient creates
energy to power the ATP
synthase complex.
• As H+ rush back into the
matrix through the ATP
synthase protein, ADP is
phosphorlyated
Oxidative Phosphorylation:
ADP  ATP
• The H+ gradient creates
energy to power the ATP
synthase complex.
• As H+ rush back into the
matrix through the ATP
synthase protein, ADP is
phosphorlyated
• This process is also
known as chemiosmosis
ETC animation
Oxidative Phosphorylation:
how many ATP are made?
• NADH from glycolysis:
– 2 ATP in electron transport chain
– exception is cardiac muscle = 3 ATP in ETC
• NADH from pyruvate transition reaction:
– 3 ATP in electron transport chain
• NADH from Kreb’s cycle:
– 3 ATP in electron transport chain
• FADH2 from Kreb’s cycle:
– 2 ATP in electron transport chain
Total ATP production from 1
molecule of glucose
Total ATP production from 1
molecule of glucose
Metabolism Handout:
• Now we will add in
the side arrows.
Storing carbohydrate energy:
Glycogenesis
• Carried out in liver and muscle
Utilizing stored energy:
Glycogenolysis:
• breaking down glycogen to glucose
• carried out in liver
making carbs from other sources:
Gluconeogenesis
• Formation of glucose
from fatty acids and
amino acids
• basically glycolysis in
reverse
• happens in the liver
Metabolism Handout:
• Now we will add in
the side arrows.
Lipid Metabolism:
digestion
• fats are digested,
absorbed and put into
chylomicrons (large
lipoprotiens).
Lipid Metabolism:
digestion
• fats are digested,
absorbed and put into
chylomicrons (large
lipoproteins).
• Chylomicrons enter the
blood stream where
triglycerides are extracted.
• The remnant of the
chylomicron goes to the
liver
Metabolism Handout:
• Now we will add in
the side arrows.
Lipid Metabolism:
digestion
• The triglycerides are broken down further
in the blood to free fatty acids + glycerol.
The fate of glycerol
• glycerol is converted
to glyceraldehyde-3phosphate
• G-3-P enters
glycolysis and then
goes through Kreb’s
cycle and the ETC.
The fate of free fatty
acids: Beta-oxidation
• Fatty acids are broken
down into 2 carbon acetic
acid fragments.
• the acetic acid is
converted to acetyl-Co A,
which enters the Krebs
cycle and then ETC
How much ATP does a 18 carbon
fatty acid chain produce?
Storing fat:
Lipogenesis
Utilizing stored energy:
lipolysis
• Breakdown of lipids
converted to G-3-P
and enters
glycolysis
converted to acetylCoA and enters
Kreb’s cycle
Ketogenesis
• If you are on a low-carb diet, starving
yourself, or diabetic:
– oxaloacetic acid (from breakdown of
glucose) levels decline and slow down the
turning of the Kreb’s cycle
– acetyl Co-A (from fatty acid breakdown)
accumulates and the liver converts it to
ketone bodies
– Ketone bodies are released into the
blood so they can be eliminated by the
kidneys
– excess ketones in blood = ketoacidosis
KREB’S
Metabolism Handout:
• Now we will add in
the side arrows.
Protein Metabolism
• Generally, proteins are not used for
energy because we need them for protein
synthesis (essential amino acids)
Ammonia
Urea
Keto Acid
pyruvate
acetyl
CoA
Kreb’s
cycle
Overview of Catabolism
• glucose =
– glycolysis
• fatty acids =
– beta-oxidation
• amino acids =
– deamination
Overview of Anabolism
We talked about:
• Glycogenolysis
• Gluconeogenesis
• Lipogenesis
Cells also use ATP to make proteins and
nucleic acids.