Nonoxidative Glycolytic Energy Sources Brooks, 2000

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Nonoxidative (Glycolytic) Energy Sources Brooks,
2000

• Incomplete breakdown of carbohydrate the
  dissolution of sugar
• Anaerobic system to re-synthesize ATP
• Eleven or twelve separate but sequential chemical
  reactions
• Glucose or glucose from glycogen
• Energy released during CHO breakdown and through
  coupled reactions, re-synthesizes ATP
• Each reaction requires presence of specific
  enzymes
• Only a few moles of ATP are possible

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Relationship between Glycolysis and Oxidative
Metabolism

• Current treatment of topic is different compared
  to your text due to recent discoveries
• Presence of lactate transporters and their
  distribution in cells tissues in humans
• Ability of mitochondria to take up and oxidize
  lactate directly
• Intracellular lactate shuttle concept
• 10x more lactate than pyruvate in resting muscle

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Glycolysis in Muscle

• The process of glycolysis extremely active in
  skeletal muscle
• Pale, white fibers contain contain large
  quantities of glycolytic enzymes
• Historically, we learned that there are two forms
  of glycolysis
• Aerobic (with oxygen)
• Anaerobic (without oxygen)
• Today we know that glycolysis proceeds to the
  next step beyond pyruvic acid to form LA EVEN
  with OXYGEN PRESENT in ABUNDANCE

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Glucose Uptake by Cells

• Depends on
• Type of tissue (muscle, liver, adipose)
• Levels of glucose in the blood and tissues
• Presence of insulin
• Physiological status of the tissue
• Most tissues require insulin to take in glucose
  (accept exercising muscle)

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Glucose Paradox

• Direct when pathway of liver glycogen synthesis
  from dietary CHO involves hepatic uptake of
  glucose
• Indirect degradation of glucose to lactate,
  followed by conversion of lactate to glycogen
• Occurs primarily in skeletal muscle
• Also occurs in RBC, adipose cells, and liver cells

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Blood Glucose During Rest Exercise

• Normal resting glucose 100mg/dl (100mg ) or
  5.55 mM
• Maintenance of blood glucose a challenge during
  exercise
• Liver plays key role in maintenance
• Low and falling blood glucose concentrations
  (hypoglycemia, glucose of ?3.5 mM, 65 mg.dl)
  associated with fatigue

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Glycolysis

• Occurs mainly in cytosol enzymes concentrated
  here
• Some glycolytic enzymes (lactate dehydrogenase)
  (LDH) exist in mitochondria and microsomes
• Equilibrium constant (Keq) for LDH is high
  meaning pyruvate not immediately entering
  mitochondria is reduced to lactate

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Glycolysis
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Lactic Acid Lactate

• At physiological pH, pyruvic and lactic acid
  molecules dissociate a hydrogen ion (H) and
  therefore are acids.
• The terms pyruvate and lactate, are the salts of
  the respective acids
• Pyruvic acid and pyruvate Lactic acid and
  lactate are generally used interchangeably

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Nicotinamide Adenine Dinucleotide (NAD)

• NAD exists in two forms NAD (oxidized) NADH
  (reduced)
• NAD transfers hydrogen ions and electrons within
  cells
• Cellular NADH/ NAD ratio (or redox) is important
  in the control of metabolism
• NADH NAD poorly diffuse across mitochondrial
  membranes

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Glycolysis Chart - Highlights

• Step 6 involves reduction of NAD to NADH
• Glycolysis proceeds slowly NADH
  shuttles/transports H and electron to
  mitochondria
• If there is insufficient mitochondrial activity
  to accept glycolytic flux (can occur in type II b
  fibers or type I during maximal exercise NADH
  is oxidized and pyruvate reduced to form lactate

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Glycolysis Chart - Highlights

• Net formation of lactate or pyruvate depends on
  relative glycolytic and mitochondrial activities
  (not on the presence of oxygen)
• Glycolytic flux in excess of mitochondrial demand
  results in lactate production simply because of
  high activity level of LDH favoring product
  formation (lactate)
• Lactate/pyruvate monocarboxylate transporters
• Transport lactate into mitochondria (under rapid
  glycolysis condition) where lactate is oxidized
  by mitochondrial LDH to pyruvate (more later)

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Control of Glycolysis

• Two control types
• Feed-forward - factors that increase G-6-P
  levels tend to stimulate glycolysis
• Stimulation of glycogenolysis by epinephrine
  contractions glucose uptake (by contraction
  insulin)
• Feedback controls - involve changes in levels of
  metabolites resulting from glycolysis

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Phosphofructokinase

• Stimulators ADP, Pi, AMP
• Inhibitors ATP, CP, citrate

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Pyruvate Dehydrogenase (PDH)

• Inhibited by high
• ATP/ADP, Acetyl-CoA/CoA, and NADH/NAD -- act
  to reduce glycolytic flux to the Krebs Cycle by
  inactivation of PDH
• Dephosphorylation of PDH activates enzyme as well
  as high Ca, decreases inATP/ADP,
  Acetyl-CoA/CoA, and NADH/NAD
  
  

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Glycogenolysis

• Skeletal muscle is heavily dependent on
  intramuscular storage form of glucoseglycogen
• During heavy muscular exercise, 80 of carbon for
  glycolysis comes from glycogen
• Depletion during heavy muscular exercise results
  in fatigue

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Glycogenolysis

• Glycogen storage - glycogen synthase
• Glycogen breakdown - phosphorylase
• Activity level is controlled by
• Hormones - epinephrine and cyclic AMP (cAMP -
  intracellular hormone)
• Ca released from sarcoplasmic reticulum
• Phosphate
• Glycogen?Glucose-1-P?Glucose-6-P

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Nicotinamide adenine dinucleotide (NAD)

• NAD - oxidized
• NADH - reduced
• NAD transfers hydrogen ions and electrons within
  cells.
• NADH/NAD ratio (or redox) - important in control
  of metabolism
• Nicotinamide is the product of a B vitamin
• Step 6 glycolysis reaction reveals hydrogen
  electrons and ions are added to NAD
• Flavine adenine dinucleotide (FAD)

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The Electron Transport Chain

• Located on the mitochondrial inner membrane
• Oxidative Phosphorylation - refers to two
  separate processes that usually function together
• Function of ETC - reducing equivalents containing
  a high-energy hydrogen and electron pair - gain
  entry into chain.

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Site of Aerobic Metabolism