From each molecule of glucose entering glycolysis: From

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Carbohydrate Metabolism
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An Overview of Metabolism
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Adenosine Tri-Phosphate (ATP)

• Link between energy releasing and energy
  requiring mechanisms
• rechargeable battery
• ADP P Energy ATP

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Mechanisms of ATP Formation

• Substrate-level phosphorylation
• Substrate transfers a phosphate group directly
• Requires enzymes
• Phosphocreatine ADP Creatine ATP
• Oxidative phosphorylation
• Method by which most ATP formed
• Small carbon chains transfer hydrogens to
  transporter (NAD or FADH) which enters the
  electron transport chain

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Metabolism

• Metabolism is all the chemical reactions that
  occur in an organism
• Cellular metabolism
• Cells break down excess carbohydrates first, then
  lipids, finally amino acids if energy needs are
  not met by carbohydrates and fat
• Nutrients not used for energy are used to build
  up structure, are stored, or they are excreted
• 40 of the energy released in catabolism is
  captured in ATP, the rest is released as heat

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Anabolism

• Performance of structural maintenance and repairs
• Support of growth
• Production of secretions
• Building of nutrient reserves

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Catabolism

• Breakdown of nutrients to provide energy (in the
  form of ATP) for body processes
• Nutrients directly absorbed
• Stored nutrients

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Cells and Mitochondria

• Cells provide small organic molecules to
  mitochondria
• Mitochondria produce ATP used to perform cellular
  functions

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Metabolism of Carbohydrates
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Carbohydrate Metabolism

• Primarily glucose
• Fructose and galactose enter the pathways at
  various points
• All cells can utilize glucose for energy
  production
• Glucose uptake from blood to cells usually
  mediated by insulin and transporters
• Liver is central site for carbohydrate metabolism
• Glucose uptake independent of insulin
• The only exporter of glucose

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Blood Glucose Homeostasis

• Several cell types prefer glucose as energy
  source (ex., CNS)

• 80-100 mg/dl is normal range of blood glucose in
  non-ruminant animals
• 45-65 mg/dl is normal range of blood glucose in
  ruminant animals
• Uses of glucose

• Energy source for cells
• Muscle glycogen
• Fat synthesis if in excess of needs

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Fates of Glucose

• Fed state
• Storage as glycogen
• Liver
• Skeletal muscle
• Storage as lipids
• Adipose tissue
• Fasted state
• Metabolized for energy
• New glucose synthesized

Synthesis and breakdown occur at all times
regardless of state... The relative rates of
synthesis and breakdown change
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immediately after eating a meal
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Glucose Metabolism

• Four major metabolic pathways
• Energy status (ATP) of body regulates which
  pathway gets energy
• Same in ruminants and non-ruminants

• Immediate source of energy
• Pentophosphate pathway
• Glycogen synthesis in liver/muscle
• Precursor for triacylglycerol synthesis

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Fate of Absorbed Glucose

• 1st Priority glycogen storage
• Stored in muscle and liver
• 2nd Priority provide energy
• Oxidized to ATP
• 3rd Priority stored as fat
• Only excess glucose
• Stored as triglycerides in adipose

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Glucose Utilization
Glycogen
Energy Stores
Adipose
Glucose
Pentose Phosphate Pathway
Glycolysis
Pyruvate
Ribose-5-phosphate
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Glucose Utilization
Glycogen
Energy Stores
Adipose
Glucose
Pentose Phosphate Pathway
Glycolysis
Pyruvate
Ribose-5-phosphate
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Glycolysis

• Sequence of reactions that converts glucose into
  pyruvate

• Relatively small amount of energy produced
• Glycolysis reactions occur in cytoplasm
• Does not require oxygen

Lactate (anaerobic)
Glucose ? 2 Pyruvate
Acetyl-CoA (TCA cycle)
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Glycolysis
Glucose 2 ADP 2 Pi
2 Pyruvate 2 ATP 2 H2O
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First Reaction of Glycolysis
Traps glucose in cells (irreversible in muscle
cells)
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Glycolysis - Summary
Glucose (6C)
2 ATP
4 ADP
2 ADP
4 ATP
2 NAD
2 NADH H
2 Pyruvate (3C)
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Pyruvate Metabolism

• Three fates of pyruvate

• Conversion to lactate (anaerobic)
• Conversion to alanine (amino acid)
• Entry into the TCA cycle via pyruvate
• dehydrogenase pathway (create ATP)

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Pyruvate Metabolism

• Three fates of pyruvate

• Conversion to lactate (anaerobic)
• Conversion to alanine (amino acid)
• Entry into the TCA cycle via pyruvate
• dehydrogenase pathway

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Anaerobic Metabolism of Pyruvate to Lactate

• Problem
• During glycolysis, NADH is formed from NAD
• Without O2, NADH cannot be oxidized to NAD
• No more NAD
• All converted to NADH
• Without NAD, glycolysis stops

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Anaerobic Metabolism of Pyruvate

• Solution
• Turn NADH back to NAD by making lactate (lactic
  acid)

(oxidized)
(reduced)
(oxidized)
(reduced)
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Anaerobic Metabolism of Pyruvate

• ATP yield
• Two ATPs (net) are produced during the anaerobic
  breakdown of one glucose
• The 2 NADHs are used to reduce 2 pyruvate to 2
  lactate
• Reaction is fast and doesnt require oxygen

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Pyruvate Metabolism - Anaerobic
Lactate Dehydrogenase
Pyruvate
Lactate
NADH NAD

• Lactate can be transported by blood to liver and
  
• used in gluconeogenesis

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Cori Cycle
Lactate is converted to pyruvate in the liver
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Pyruvate Metabolism

• Three fates of pyruvate

• Conversion to lactate (anaerobic)
• Conversion to alanine (amino acid)
• Entry into the TCA cycle via pyruvate
• dehydrogenase pathway

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Pyruvate metabolism

• Convert to alanine and export to blood

Keto acid Amino acid
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Pyruvate Metabolism

• Three fates of pyruvate

• Conversion to lactate (anaerobic)
• Conversion to alanine (amino acid)
• Entry into the TCA cycle via pyruvate
• dehydrogenase pathway

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Pyruvate Dehydrogenase Complex (PDH)

• Prepares pyruvate to enter the TCA cycle

Aerobic Conditions
Electron Transport Chain
TCA Cycle
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PDH - Summary
Pyruvate
2 NAD
2 NADH H
CO2
Acetyl CoA
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TCA Cycle

• In aerobic conditions TCA cycle links pyruvate to
  oxidative phosphorylation
• Occurs in mitochondria
• Generates 90 of energy obtained from feed
• Oxidize acetyl-CoA to CO2 and capture potential
  energy as NADH (or FADH2) and some ATP

• Includes metabolism of carbohydrate, protein,
  and fat

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TCA Cycle - Summary
Acetyl CoA
3 NAD
3 NADH H
2 CO2
1 FAD
1 FADH2
1 ADP
1 ATP
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Oxidative Phosphorylation and the Electron
Transport System

• Requires coenzymes (NAD and FADH) as H carriers
  and consumes oxygen
• Key reactions take place in the electron
  transport system (ETS)
• Cytochromes of the ETS pass H2s to oxygen,
  forming water

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Oxidation and Electron Transport

• Oxidation of nutrients releases stored energy
• Feed donates H
• Hs transferred to co-enzymes
• NAD 2H 2e- NADH H
• FAD 2H 2e- FADH2

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So, What Goes to the ETS???

• From each molecule of glucose entering
  glycolysis
• From glycolysis 2 NADH
• From the TCA preparation step (pyruvate to
  acetyl-CoA) 2 NADH
• From TCA cycle (TCA) 6 NADH and 2 FADH2
• TOTAL 10 NADH 2 FADH2

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Electron Transport Chain

• NADH H and FADH2 enter ETC
• Travel through complexes I IV
• H flow through ETC and eventually attach to O2
  forming water
• NADH H 3 ATP
• FADH2 2 ATP

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Electron Transport Chain
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Total ATP from Glucose

• Anaerobic glycolysis 2 ATP 2 NADH
• Aerobic metabolism glycolysis TCA
• 31 ATP from 1 glucose molecule

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Volatile Fatty Acids

• Produced by bacteria in the fermentation of
  pyruvate
• Three major VFAs
• Acetate
• Energy source and for fatty acid synthesis
• Propionate
• Used to make glucose through gluconeogenesis
• Butyrate
• Energy source and for fatty acid synthesis
• Some use and metabolism (alterations) by rumen
  wall and liver before being available to other
  tissues

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Use of VFA for Energy

• Enter TCA cycle to be oxidized
• Acetic acid
• Yields 10 ATP
• Propionic acid
• Yields 18 ATP
• Butyric acid
• Yields 27 ATP
• Little butyrate enters blood

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Utilization of VFA in Metabolism
Acetate Energy Carbon source for fatty
acids Adipose Mammary gland Not used for net
synthesis of glucose Propionate Energy
Primary precursor for glucose synthesis Butyrate
Energy Carbon source for fatty acids - mammary
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Effect of VFA on Endocrine System
Propionate Increases blood glucose Stimulates
release of insulin Butyrate Not used for
synthesis of glucose Stimulates release of
insulin Stimulates release of glucagon Increases
blood glucose Acetate Not used for synthesis of
glucose Does not stimulate release of
insulin Glucose Stimulates release of insulin
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A BRIEF INTERLUDE
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Need More Energy (More ATP)??

• Working animals
• Horses, dogs, dairy cattle, hummingbirds!
• Increase carbon to oxidize
• Increased gut size relative to body size
• Increased feed intake
• Increased digestive enzyme production
• Increased ability to process nutrients
• Increased liver size and blood flow to liver
• Increased ability to excrete waste products
• Increased kidney size, glomerular filtration rate
• Increased ability to deliver oxygen to tissues
  and get rid of carbon dioxide
• Lung size and efficiency increases
• Heart size increases and cardiac output increases
• Increase capillary density
• Increased ability to oxidize small carbon chains
• Increased numbers of mitochondria in cells
• Locate mitochondria closer to cell walls (oxygen
  is lipid-soluble)

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Hummingbirds

• Lung oxygen diffusing ability 8.5 times greater
  than mammals of similar body size
• Heart is 2 times larger than predicted for body
  size
• Cardiac output is 5 times the body mass per
  minute
• Capillary density up to 6 times greater than
  expected

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Rate of ATP Production(Fastest to Slowest)

• Substrate-level phosphorylation
• Phosphocreatine ADP Creatine ATP
• Anaerobic glycolysis
• Glucose Pyruvate Lactate
• Aerobic carbohydrate metabolism
• Glucose Pyruvate CO2 and H2O
• Aerobic lipid metabolism
• Fatty Acid Acetate CO2 and H2O

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Potential Amount of Energy Produced (Capacity
for ATP Production)

• Aerobic lipid metabolism
• Fatty Acid Acetate CO2 and H2O
• Aerobic carbohydrate metabolism
• Glucose Pyruvate CO2 and H2O
• Anaerobic glycolysis
• Glucose Pyruvate Lactate
• Substrate-level phosphorylation
• Phosphocreatine ADP Creatine ATP

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Glucose Utilization
Glycogen
Energy Stores
Adipose
Glucose
Pentose Phosphate Pathway
Glycolysis
Pyruvate
Ribose-5-phosphate
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Pentose Phosphate Pathway

• Secondary metabolism of glucose
• Produces NADPH
• Similar to NADH
• Required for fatty acid synthesis
• Generates essential pentoses
• Ribose
• Used for synthesis of nucleic acids

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Glucose Utilization
Glycogen
Energy Stores
Adipose
Glucose
Pentose Phosphate Pathway
Glycolysis
Pyruvate
Ribose-5-phosphate
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Energy Storage

• Energy from excess carbohydrates (glucose) stored
  as lipids in adipose tissue
• Acetyl-CoA (from TCA cycle) shunted to fatty acid
  synthesis in times of energy excess
• Determined by ATPADP ratios
• High ATP, acetyl-CoA goes to fatty acid synthesis
• Low ATP, acetyl CoA enters TCA cycle to generate
  MORE ATP

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Glucose Utilization
Glycogen
Energy Stores
Adipose
Glycogenesis
Glucose
Pentose Phosphate Pathway
Glycolysis
Pyruvate
Ribose-5-phosphate
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Glycogenesis

• Liver
• 710 of wet weight
• Use glycogen to export glucose to the bloodstream
  when blood sugar is low
• Glycogen stores are depleted after approximately
  24 hrs of fasting (in humans)
• De novo synthesis of glucose for glycogen

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Glycogenesis

• Skeletal muscle
• 1 of wet weight
• More muscle than liver, therefore more glycogen
  in muscle, overall
• Use glycogen (i.e., glucose) for energy only (no
  export of glucose to blood)
• Use already-made glucose for synthesis of glycogen

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Fates of Glucose

• Fed state
• Storage as glycogen
• Liver
• Skeletal muscle
• Storage as lipids
• Adipose tissue
• Fasted state
• Metabolized for energy
• New glucose synthesized

Synthesis and breakdown occur at all times
regardless of state... The relative rates of
synthesis and breakdown change
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Fasting Situation in Non-Ruminants

• Where does required glucose come from?

• Glycogenolysis
• Lipolysis
• Proteolysis

• Breakdown or mobilization of glycogen stored by
  glucagon
• Glucagon - hormone secreted by pancreas during
  times of fasting

• Mobilization of fat stores stimulated by
  glucagon and epinephrine
• Triglyceride glycerol 3 free fatty acids
• Glycerol can be used as a glucose precursor

• The breakdown of muscle protein with release of
  amino acids
• Alanine can be used as a glucose precursor

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In a fasted state, substrates for glucose
synthesis (gluconeogenesis) are released from
storage
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Gluconeogenesis

• Necessary process
• Glucose is an important fuel
• Central nervous system
• Red blood cells
• Not simply a reversal of glycolysis
• Insulin and glucagon are primary regulators

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Gluconeogenesis

• Vital for certain animals
• Ruminant species and other pre-gastric fermenters
• Convert carbohydrate to VFA in rumen
• Little glucose absorbed from small intestine
• VFA can not fuel CNS and RBC
• Feline species
• Diet consists primarily of fat and protein
• Little to no glucose absorbed
• Glucose conservation and gluconeogenesis are
  vital to survival

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Gluconeogenesis

• Synthesis of glucose from non-carbohydrate
  precursors during fasting in monogastrics

• Glycerol
• Amino acids
• Lactate
• Pyruvate
• Propionate
• There is no glucose synthesis from fatty acids

Supply carbon skeleton
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Carbohydrate Comparison

• Primary energy substrate
• Primary substrate for fat synthesis
• Extent of glucose absorption from gut

• MOST monogastrics glucose
• Ruminant/pre-gastric fermenters VFA
• MOST monogastrics glucose
• Ruminant acetate
• MOST monogastrics extensive
• Ruminant little to none

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Carbohydrate Comparison

• Cellular demand for glucose
• Importance of gluconeogenesis

• Nonruminant high
• Ruminant high
• MOST monogastrics less important
• Ruminant very important