Cellular Metabolism
• Energy as it relates to Biology
• Metabolism
– Catabolism (ATP production)
• Glycolysis and the TCA Cycle
– Anabolism (Synthetic pathways)
• Protein Synthesis
Metabolism
• Definition = “All chemical reactions that take
place within an organism.”
• Metabolic pathways = network of linked reactions
• http://www.youtube.com/watch?v=ClXcQ0
WFjkk&feature=related
Glycolysis
• From 1 glucose (6 carbons) to 2
pyruvate (3 carbons) molecules
• Main catabolic pathway of cytoplasm
• Does not require O2  common for
(an)aerobic catabolism
• Starts with phosphorylation of
Glucose to Glucose 6-P
Pyruvate has 2 Possible Fates:
Anaerobic catabolism:
Pyruvate
Lactate
Aerobic catabolism:
Pyruvate
Citric Acid Cycle
Intermediate Step
Glycolysis
FAD and NAD
• FAD = B2 (Riboflavin)
• NAD = B3 (Niacin)
• Acetyl Co A = B1 (Thiamine)
Final step:
Electron Transport System
• Chemiosmotic theory / oxidative phosphorylation
• Transfers energy from NADH and FADH2 to ATP
(via e- donation and H+ transport)
• Mechanism: Energy released by
movement of e- through transport system
is stored temporarily in H+ gradient
• NADH produces a maximum of 2.5 ATP
FADH2 produces a maximum of 1.5 ATP
• 1 ATP formed per 2H+ shuttled through ATP
Synthase
Organelles
• http://www.youtube.com/watch?v=_PgjsfY
71AM&feature=related
• http://www.youtube.com/watch?v=xbJ0nbz
t5Kw&feature=related
Electron Transport Chain
• On the inner membrane of the
mitochondria
– Protein complexes including enzymes and
iron-containing proteins called cytochromes
• Chemiosmotic Theory
– Movement of electrons through the etc to
produce ATP
Steps to produce ATP
• Pairs of high-energy electrons pass from complex to
complex along the etc.
• Energy released by these reactions is used to pump H+
from the mitochondrial matrix into the intermembrane
space.
• The movement of protons creates a concentration
gradient
• As the protons move down their concentration gradient
into the matrix potential energy stored in the
concentration gradient is transferred to the high –energy
bond of ATP
Oxidative Phosphorylation
• Oxygen is required as the final electron
and proton acceptor
ATPsynthase
• When the protons move back into the
mitochondrial matrix through a pore in
ATPsynthase stored energy is converted into
chemical-bond energy
• The ATPsynthase transfers KE to the highenergy phosphate bond of ATP
• A portion of this energy transfer is released as
heat and absorbed into the blood
Electron Transport Chain
http://www.youtube.com/watch?v=3y1
dO4nNaKY&feature=related
In the absence of oxygen, which of the
following processes can still occur?
A. Glycolysis
B. The Kreb’s cycle
C. Electron transport chain
D. Oxidative phosphorylation
Beta-oxidation of fatty acids yields
A.
B.
C.
D.
E.
Glucose
Pyruvic acid
Lactic acid
Citric acid
Acetyl CoA
If oxygen is not present in the intermediate
step, the end product is
A.
B.
C.
D.
E.
Pyruvate
Lactic acid
Acetyl coenzyme A
Carbon dioxide and water
Fatty Acids
Acetyl CoA + _____________ produces
Citric Acid.
A. Pyruvic Acid
B. Succinyl Co A
C. αKetoglutarate
D. Oxaloacetic Acid
E. Fumarate
The final electron acceptor in the process of
oxidative phosphorylation is
A.
B.
C.
D.
E.
NAD
Oxygen
FAD
Carbon dioxide
Water
Which cytochrome is FAD attracted
to in the ETC?
A. Complex I
B. Complex II
C. Cyt b-c1
D. Cyt a
In the chemiosmotic theory, how many ATP are
ultimately produced from the two electrons from
the hydrogen atoms carried by NAD?
A. 2
B. 3
C. 5
D. 7
E. 9
Which cytochrome comes after Q in the
electron transport chain?
A. Cyt b
B. Cyt c
C. Cyt a
D. Cyt a3
E. Cyt f
Which vitamins participate in the
citric acid cycle as hydrogen
carriers?
A.
B.
C.
D.
Pyroxidine and thiamine
Niacin and ascorbic acid
Riboflavin and niacin
Thiamine and biotin
Where in the mitochondria does the
Citric Acid Cycle take place?
A. Inner membrane
B. Outer membrane
C. Intermembrane space
D. Matrix
Glycogen Synthesis
Made from glucose
Stored in all cells but especially in
• Liver (keeps 4h glycogen reserve for between meals)
• Skeletal Muscle  muscle contraction
Gluconeogenesis
Glycolysis in reverse
From glycerol, aa and lactate
All cells can make G-6-P, only liver and
Kidney can make glucose
Water Soluble Vitamins
• B1 (Thiamine)
– Part of coenzyme cocarboxylase
• Transformation of pyruvic acid to acetyl CoA
– Deficits
• Beriberi
–
–
–
–
–
–
Decreased appetite
Vision disturbances
Unsteady gait
Loss of memory and confusion
Fatigue
tachycardia
Water Soluble Vitamins
• B2 (Riboflavin)
– FAD and FMN
• Hydrogen acceptors in body
– Deficits
•
•
•
•
Cracking of lips
Tongue turns purple red and shiny
Light sensitivity
Decreased energy
Water Soluble Vitamins
• B3 (Niacin)
– Constituent of NAD
– Deficits
•
•
•
•
•
•
•
•
•
Listlessness
Headache
Weight loss and loss of appetite
Sore red tongue and lips
Nausea
Vomiting
Diarrhea
Photosensitivity
Cracked and ulcerated skin
Water Soluble Vitamins
• B6 (Pyridoxine)
– Coenzyme pyridoxal phosphate
• Functions in amino acid metabolism
• Formation of antibodies and hemoglobin
– Deficits
• Increased risk of heart disease
• Seborrhea around eyes and mouth
• In infants: nervous irritability and convulsions
Water Soluble Vitamins
• B5 (Pantothenic acid)
– Coenzyme A
– Deficits
•
•
•
•
Loss of appetite
Abdominal pain
Depression
Muscle spasms
Water Soluble Vitamins
• Biotin
– Coenzyme for Krebs cycle
– Deficits
•
•
•
•
•
•
•
Scaly skin
Muscle pain
Pallor
Anorexia
Nausea
Fatigue
Elevated blood cholesterol
Water Soluble Vitamins
• C (Ascorbic Acid)
– Antioxidant
– Formation of connective tissue
– Converts tryptophan to serotonin
– Enhances iron absorption
– Deficits
• Joint pains and poor both and tooth growth
• Poor wound healing
• scurvy
Water Soluble Vitamins
• B12 (Cyanocobalamin)
– Coenzyme in gastrointestinal cells, nervous tissue
and bone marrow
– Synthesis of DNA
– Division of erythrocytes
– Deficit
• Pernicious Anemia
–
–
–
–
Pallor
Anorexia
Dyspnea
Weight loss
Water Soluble Vitamins
• Folic Acid
– Coenzymes for synthesis of methionine and other amino
acids
– DNA synthesis
– Formation of red blood cells
– Formation of normal neural tube in embryonic
development
– Deficits
•
•
•
•
•
•
•
Megaloblastic anemia
Gastrointestinal disturbances
Diarrhea
Spina bifida in new born
Low birth weight
Neurological deficits
Increased risk of heart attack and stroke
Fat Soluble Vitamins
• A (Retinol)
– Synthesis of photoreceptor pigments
– Development of teeth and bone
– Antioxidant
– Deficits
•
•
•
•
Night blindness
Dry skin and hair
Dry eyes
Defects to developing embryo
Fat Soluble Vitamins
• D (Antirachitic factor)
–
–
–
–
–
Functionally a hormone
Increases calcium in blood by enhancing absorption
Acts with PTH to remove calcium from bones
Assists in blood clotting mechanism
Deficits
• Demineralization of bones and teeth
– Rickets or osteomalacia
– Restless muscle syndrome
Fat Soluble Vitamins
• E (Antisterility factor)
–
–
–
–
Antioxidant for free radicals
Prevents oxidation of fatty acids and cholesterol
Prevents atherosclerosis
Deficits
• Possible decrease in life span
• K (Coagulation vitamin)
– Formation of clotting proteins
– Deficits
• Easy bruising and prolonged bleeding
Protein Catabolism
• Proteases
• Peptidases
• Deamination (removal
of the NH3)
– NH3 becomes urea
• Pyruvate, Acetyl CoA,
TCA intermediates are
left.
Transamination
Lipid Catabolism
• Lipolysis
– Lipases break lipids
into glycerol (3-C)
• Glycerol enters the
glycolytic pathway
– Called β-oxidation
Beta-Oxidation
Synthetic Pathways
Anabolic reactions synthesize large
biomolecules
Unit molecules
Glucose
Amino Acids
Macromolecules
nutrients &
energy required Polysaccharides
Lipids
DNA
Protein
Metabolism
Catabolism
 Energy
Anabolism
 Synthesis
Energy transferred commonly measured in calories:
1 cal =  1 g of H2O by 1° C
1 Kcal =  temp. of 1L H2O by 1o C.
= Calorie (capital C)
Energy released in catabolic reactions is trapped in
1) Phosphate bonds
2) Electrons
Control of Metabolic Pathways
1.
Enzyme concentration (already
covered)
2.
Enzyme modulators
- Feedback- or end product
inhibition
- Hormones
- Other signaling molecules
3.
Different enzymes for
reversible reactions
4.
Enzyme isolation
5.
Energy availability (ratio of
ADP to ATP)
Review:
• Energy = capacity to do work
– Usually from ATP
• Enzymes = biological catalyst
– Lower activation energy
– Return to original state
– Opportunity for control
Catabolic Pathways: ATP-Regeneration
Amount of ATP produced reflects on
usefulness of metabolic pathways:
Aerobic pathways
Anaerobic pathways
Different
biomolecules enter
pathway at
different points
ATP = Energy Carrier of Cell (not very useful
for energy storage)
ATP Cycle
ATP : ADP ratio determines status of ATP synthesis reactions
The Steps of
Glycolysis
Net gain?
Citric Acid Cycle
Other names ?
Takes place in ?
Energy Produced:
1 ATP
3 NADH
1 FADH2
Electron transport
System
Waste – 2 CO2
Energy Yield of Krebs Cycle
NADH
NADH
NADH
FADH2
Summary of
CHO catabolism
Cellular
Respiration
Maximum potential
yield for aerobic
glucose metabolism:
30-32 ATP
synthesized from
ADP
H2O is a byproduct