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Metabolism
• Metabolism – all chemical reactions necessary
to maintain life.
– Anabolic reactions – synthesis of larger molecules
from smaller ones. (dehydration synthesis)
– Catabolic reactions –(hydrolysis) of complex
structures into simpler ones.
• Cellular respiration – food is broken down within
cells to their basic organic building blocks.
– The energy captured from the food is used to
produce ATP
Cellular Energy
• All cells require a constant supply of ATP. It is essentially the
currency that all cells use for energy. Without a constant supply
the cell will die.
• Specific proteins in the cell are capable of hydrolyzing ATP
ATP
ADP + P (energy released for reactions)
ATPase
ADP(adenosine diphosphate) and a phosphate group synthesize
ATP by creating high energy bond between the 2nd and 3rd
phosphate group
ADP + P
ATP ( energy storing)
The energy from eating organic compounds provide the energy to
create ATP
Cellular Energy
• The energy stored in the phosphate bonds of ATP originally
comes from the plants ability to capture radiant energy from the
sun. This allows the plants to convert inorganic molecules into
organic molecules. This process called photosynthesis.
Radiant energy
• 6H2O + 6CO2 + 36 ATP  C6H12O6 + 6O2 + 36 ADP +36 P
The energy is stored within the H’s of organic molecules
(monosaccharides, fatty acids and amino acids).
• We eat the plants and animals that eat the plants. Our cells can
extract the energy stored within the H’s and produce ATP
• The more H’s food has the more energy it contains.
Energy Metabolism
• During cellular respiration the energy stored in a
glucose’s H are removed and taking to a specific part
to the cell to harness the energy and make ATP.
Several B vitamins are required for this process.
• 2 B-vitamin derivatives coenzymes NAD (niacin) and
FAD (Riboflavin) are required for oxidation-reduction
reactions to remove the hydrogen.
• These enzymes oxidizes sugar intermediates
(loss of an electron/hydrogen atom)
NAD
NADH reduced
(gain of an electron/hydrogen atom)
FAD
FADH2 reduced
• the reduced coenzymes are taken to the cristea of
mitochondria where 32 of the 36 ATP’s are formed.
Cellular Respiration
Cellular Respiration
•
Since all carbohydrates are transformed into
glucose, it is essentially glucose metabolism
• Oxidation of glucose is shown by the overall
reaction:
C6H12O6 + 6O2  6H2O + 6CO2 + 36 ATP + heat
• Glucose is oxidized in three pathways
1. Glycolysis (cytoplasm) =sugar/lyses (splitting)
2. Krebs cycle (matrix of mitochondria)
3. The electron transport chain (cristae of
mitochondria)
Glycolysis: Phase 1 and 2
•
Phase 1: Sugar activation
– Two ATP molecules are
hydrolyzed providing the energy
required to start Glycolysis
– Glucose is into converted into
fructose-1,6-diphosphate after 2
hydrolyzed phosphates for each
ATP attach to the Glucose.
•
Phase 2: Sugar cleavage
– Fructose-1,6-bisphosphate is
cleaved into two
3-carbon isomers
• Bishydroxyacetone
phosphate( gets converted
to G3P)
• Glyceraldehyde 3-phosphate
( G3P) Also known as
Phosphglyceraldahyde
Glycolysis: Phase 3
• Phase 3: Oxidation and
ATP formation
– The 3-carbon sugars are
oxidized (reducing NAD+
forming NADH)
– Inorganic phosphate
groups (Pi) are attached to
each oxidized fragment
– The terminal phosphates
are cleaved and captured
by ADP to form four ATP
molecules by substrate
level phosphorylation.
Glycolysis: Phase 3
• The final products
are:
– Two pyruvic acid
molecules
– Two NADH molecules
(reduced NAD+)
– A net gain of two ATP
molecules
Glycolysis Overview
• A three-phase pathway in which:
– Glucose is oxidized into pyruvic acid
– NAD+ is reduced to NADH
– 2 ATP is synthesized by substrate-level
phosphorylation
• Pyruvic acid:
– Moves on to the Krebs cycle in an aerobic pathway
– Is reduced to lactic acid in an anaerobic environment
Intermediate Step For Krebs Cycle
•
•
Occurs in the mitochondria and is
fueled by pyruvic acid
If there is enough O2 present
pyruvic acid is converted to acetyl
CoA in three main steps:
1. Oxidation
• Hydrogen atoms are
removed from pyruvic acid
• NAD+ is reduced to NADH
2. Decarboxylation
• Carbon is removed from
pyruvic acid in the form of
Carbon dioxide forming
acetic acid
3. acetic acid is combined with
coenzyme A to form acetyl CoA
Pyruvic Acid → Acetyl CoA
During this step the products
are:
– 2 molecules of CO2
– 2 molecules of NADH
– 2 molecules of Acetyl CoA
Krebs Cycle
End Products of Krebs Cycle
• 2 acetyl CoA entering the
Krebs Cycle will yield:
– 6 NADH and 2 FADH2
shuttles H to electron
transport chain located on
the cristea.
– ATP will be produced by
oxidative phosphorylation
– 4 CO2
– 2 ATP via substrate level
Phosphorylation.
Electron Transport Chain
Electron Transport Chain (ETC)
• The NADH and FADH2 from glycolysis, acetyl CoA
formation and the Krebs cycle are shuttled to the
cristea (inner membrane of the mitochondria)
• The cristea has 3 integral membrane proteins that
pump protons into the intermembrane space from the
matrix. This creates a proton gradient.
• NADH drops a pair of electrons (e-) at the first protein
complex while FADH2 goes to the second complex.
• The oxidation of NADH and FADH2 back to NAD and
FAD enables these co-enzymes to travel back to the
cytoplasm and mitochondria to oxidize another sugar
molecule.
Electron Transport Chain
• The e- energize the first protein complex results in 2
protons (H+) from the matrix to be pumped into the
intermembrane space.
• The e- are shuttled from the first protein complex to the
second one by Co-enzyme Q10
– 2 more protons get pumped out into the
intermembrane space.
• Cytochrome (Cyt c) moves the e- to the final protein
complex
– 2 more protons get pumped out into the
intermembrane space.
• This creates a high H+ concentration in the
intermembrane space
ATP Synthase.
• The H+ diffuse along their concentration gradient back
into the matrix through the channel protein ATP
synthase.
• As the H+ go through the ATP synthase complex energy
is created to phosphorylate ADP to make ATP
– (Oxidative Phosphorylation) 32-34 ATP produced way
• In order to ensure a H+ gradient O2 must be present in
the mitochondria.
• The electrons are transferred to the O2 at the last
enzyme complex making O2 especially negative
• O2- atom combined with the H+ that have diffused back
into the matrix from the intermembrane space to form
water (H2O)
• O2 must work as the final electron acceptor in the ETC
Lactic Acid Fermentation
• If there is not enough O2
present in the
Mitochondria the NADH
will return to the cytosol
and reduce pyruvic acid
to form Lactic acid.
• Lactic acid is another
source for ATP
• Lactic acid will be
oxidized back to pyruvic
acid once O2 is present
again
Clinical Connection
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There are several forms of Anemia.
Iron deficiency is one of the most common types
Iron is critical for O2 carrying hemoglobin
Iron is also vital for transferring electrons along
the chain.
Symptoms include SOB, fatigue, weakness and
unusual food cravings ( pica)
More common in the elderly
Vitamin C aids in the absorption of iron
Iron is important for energy production!
Glycogen Metabolism
• ATP is quickly used after it is formed -- it is not a storage
molecule
– extra glucose will not be oxidized, it will be stored
• Glycogenesis -- synthesis of glycogen
– stimulated by insulin (average adult contains 450 g) primarily the liver
and Type II muscle fibers.)
• Glycogenolysis -- glycogen  glucose
– stimulated by glucagon and epinephrine
– only liver cells can release glucose back into blood
• Gluconeogenesis -- synthesis of glucose from noncarbohydrates, such as Lactic acid, pyruvic acid, glycerol
and amino acids
– Takes place mainly in the liver.
– Protects the body, especially the brain, from the damaging effects of
hypoglycemia by ensuring ATP synthesis can continue
Lipids
• Triglycerides are stored in adipocytes
– constant turnover of molecules every 3 weeks
• released into blood, transported and either oxidized or
redeposited in other fat cells
• Lipogenesis = synthesizing fat from other sources
– amino acids and sugars used to make fatty acids and
glycerol
• Lipolysis = breaking down fat for fuel
– glycerol is converted to PGAL and enters glycolysis
– fatty acids are broken down 2 carbons at a time to
produce acetyl-CoA (beta oxidation)
Lipid Metabolism
• Glycerol is converted to glyceraldehyde phosphate
– Glyceraldehyde is ultimately converted into acetyl
CoA
– Acetyl CoA enters the Krebs cycle
• Fatty acids undergo beta oxidation which produces:
– Two-carbon acetic acid fragments, which enter the
Krebs cycle
– A 24 carbon fatty acid can produce 12 acetic acids.
• 36 total NADH and 12 FADH2 = 120 ATP compared to 32
from glucose
• Fats are the best fuel source
Lipid Metabolism
Lipogenesis and Lipolysis
• Excess dietary glycerol and fatty acids undergo
lipogenesis to form triglycerides.
– Elevated triglycerides is a major cardiac risk factor.
• Lipolysis, the breakdown of stored fat, is essentially
lipogenesis in reverse
• Oxaloacetic acid is necessary for the complete oxidation
of fat
– Fat will only burn in a carbohydrate flame!
– Without Carbs fatty acid oxidation is shut down.
– Acetyl CoA is converted into ketones (ketogenesis)
Ketogenesis
• Fatty acids catabolized into acetyl groups (by beta-oxidation in
mitochondrial matrix) may
– enter citric acid cycle as acetyl-CoA if sugar is present
– undergo ketogenesis is the absence if carbohydrates
• metabolized by liver to produce ketone bodies
– acetoacetic acid
– -hydroxybutyric acid
– acetone
• rapid or incomplete oxidization of fats raises blood
ketone levels (ketosis) and may lead to a pH imbalance
(ketoacidosis)
• pH changes can denature many enzymes.
• This is very common in uncontrolled diabetics and
people on no carb diets.
Lipogenesis and Lipolysis Pathways
Proteins
• Amino acid pool - dietary amino acids plus 100 g of
tissue protein broken down each day into free amino
acids
• May be used to synthesize new proteins
• As fuel – Only as a last resort
– first must be deaminated (removal of NH2)--what
remains is converted to pyruvic acid, acetyl-CoA
or part of citric acid cycle
– High protein diets are popular because you may
experience rapid weight loss. This is the result of
your kidneys pulling more water out of your body
to get rite of the excessive nitrogenous wastes
Pathways of Amino Acid Metabolism