Cellular Metabolism

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Cellular Metabolism

• Energy as it relates to Biology
• Metabolism
• Catabolism (ATP production)
• Glycolysis and the TCA Cycle
• Anabolism (Synthetic pathways)
• Protein Synthesis

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Metabolism

• Definition All chemical reactions that take
  place within an organism.
• Metabolic pathways network of linked reactions

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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

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Pyruvate has 2 Possible Fates
Anaerobic catabolism Pyruvate
Lactate
Aerobic catabolism Pyruvate
Citric Acid Cycle
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Intermediate Step
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Glycolysis
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FAD and NAD

• FAD B2 (Riboflavin)
• NAD B3 (Niacin)
• Acetyl Co A B1 (Thiamine)

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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

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Organelles
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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

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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

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Oxidative Phosphorylation

• Oxygen is required as the final electron and
  proton acceptor

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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 high-energy
  phosphate bond of ATP
• A portion of this energy transfer is released as
  heat and absorbed into the blood

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Electron Transport Chain
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In the absence of oxygen, which of the following
processes can still occur?

1. Glycolysis
2. The Krebs cycle
3. Electron transport chain
4. Oxidative phosphorylation

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Beta-oxidation of fatty acids yields

• Glucose
• Pyruvic acid
• Lactic acid
• Citric acid
• Acetyl CoA

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If oxygen is not present in the intermediate
step, the end product is

• Pyruvate
• Lactic acid
• Acetyl coenzyme A
• Carbon dioxide and water
• Fatty Acids

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Acetyl CoA _____________ produces Citric Acid.

• Pyruvic Acid
• Succinyl Co A
• aKetoglutarate
• Oxaloacetic Acid
• Fumarate

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The final electron acceptor in the process of
oxidative phosphorylation is

• NAD
• Oxygen
• FAD
• Carbon dioxide
• Water

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Which cytochrome is FAD attracted to in the ETC?

1. Complex I
2. Complex II
3. Cyt b-c1
4. Cyt a

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In the chemiosmotic theory, how many ATP are
ultimately produced from the two electrons from
the hydrogen atoms carried by NAD?

• 2
• 3
• 5
• 7
• 9

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Which cytochrome comes after Q in the electron
transport chain?

1. Cyt b
2. Cyt c
3. Cyt a
4. Cyt a3
5. Cyt f

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Which vitamins participate in the citric acid
cycle as hydrogen carriers?

• Pyroxidine and thiamine
• Niacin and ascorbic acid
• Riboflavin and niacin
• Thiamine and biotin

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Where in the mitochondria does the Citric Acid
Cycle take place?

• Inner membrane
• Outer membrane
• Intermembrane space
• Matrix

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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
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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

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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

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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

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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

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Water Soluble Vitamins

• B5 (Pantothenic acid)
• Coenzyme A
• Deficits
• Loss of appetite
• Abdominal pain
• Depression
• Muscle spasms

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Water Soluble Vitamins

• Biotin
• Coenzyme for Krebs cycle
• Deficits
• Scaly skin
• Muscle pain
• Pallor
• Anorexia
• Nausea
• Fatigue
• Elevated blood cholesterol

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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

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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

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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

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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

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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

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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

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Protein Catabolism

• Proteases
• Peptidases
• Deamination (removal of the NH3)
• NH3 becomes urea
• Pyruvate, Acetyl CoA, TCA intermediates are left.

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Transamination
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Lipid Catabolism

• Lipolysis
• Lipases break lipids into glycerol (3-C)
• Glycerol enters the glycolytic pathway
• Called ß-oxidation

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Beta-Oxidation
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Synthetic Pathways
Anabolic reactions synthesize large biomolecules
Unit molecules Macromolecules
nutrients energy required
Polysaccharides Lipids DNA Protein
Glucose Amino Acids
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Metabolism
Anabolism ? Synthesis
Catabolism ? Energy
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
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Control of Metabolic Pathways

• Enzyme concentration (already covered)
• Enzyme modulators
• - Feedback- or end product inhibition
• - Hormones
• - Other signaling molecules
• Different enzymes for reversible reactions
• Enzyme isolation
• Energy availability (ratio of ADP to ATP)

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Review

• Energy capacity to do work
• Usually from ATP
• Enzymes biological catalyst
• Lower activation energy
• Return to original state
• Opportunity for control

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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
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ATP Energy Carrier of Cell (not very useful
for energy storage)
ATP ADP ratio determines status of ATP
synthesis reactions
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The Steps of Glycolysis
Net gain?
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Citric Acid Cycle

• Other names ?
• Takes place in ?
• Energy Produced
• 1 ATP
• 3 NADH
• 1 FADH2
• Waste 2 CO2

Electron transport System
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Energy Yield of Krebs Cycle
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Cellular Respiration
Summary of CHO catabolism
Maximum potential yield for aerobic glucose
metabolism 30-32 ATP synthesized from ADP H2O is
a byproduct