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An Overview of Metabolism
Adenosine Tri-Phosphate (ATP)
Link between energy releasing and
energy requiring mechanisms
rechargeable battery
Skeletal muscle
all times
Storage as lipids regardless of state...
Adipose tissue
Fasted state The relative rates of
Metabolized for energy synthesis and
New glucose synthesized breakdown change
High Blood Glucose
Pancreas
Insulin Glycogen
Muscle
Glucose absorbed
Glucose
Pentose Glycolysis
Phosphate
Pathway
Ribose-5-phosphate Pyruvate
Glucose Utilization
Energy
Adipose Stores Glycogen
Glucose
Pentose Glycolysis
Phosphate
Pathway
Ribose-5-phosphate Pyruvate
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)
Glycolysis
Glucose + 2 ADP + 2 Pi
2 Pyruvate + 2 ATP + 2 H2O
First Reaction of Glycolysis
2 NAD
2 NADH + H
2 Pyruvate (3C)
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)
Pyruvate Metabolism
Three fates of pyruvate:
Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway
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
Anaerobic Metabolism
of Pyruvate
Solution:
Turn NADH back to NAD+ by making lactate (lactic acid)
(reduced) (oxidized)
NADH + H+ NAD+
COO COO
C O HC OH
Lactate dehydrogenase
CH3 CH3
Pyruvate Lactate
(oxidized) (reduced)
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
Pyruvate Metabolism -
Anaerobic
Lactate Dehydrogenase
Pyruvate Lactate
NADH NAD+
Lactate is converted to
pyruvate in the liver
Pyruvate Metabolism
Three fates of pyruvate:
Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway
Pyruvate metabolism
Convert to alanine and export to blood
Glutamate -Ketoglutarate
COO COO
C O HC NH 3+
Alanine amino transferase
CH3 (AAT) CH3
Pyruvate Alanine
Keto acid Amino acid
Pyruvate Metabolism
Three fates of pyruvate:
Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway
Pyruvate Dehydrogenase
Complex (PDH)
Prepares pyruvate to enter the TCA cycle
Aerobic Conditions
Electron TCA Cycle
Transport
Chain
PDH - Summary
Pyruvate
2 NAD
2 NADH + H
CO2
Acetyl CoA
TCA Cycle
In aerobic conditions TCA cycle links
pyruvate to oxidative phosphorylation
Occurs in mitochondria
Generates 90% of energy obtained from feed
Includes metabolism of carbohydrate,
protein, and fat
3 NADH + H
2 CO2
1 FAD
1 FADH2
1 ADP
1 ATP
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
Oxidation and Electron Transport
Oxidation of nutrients releases stored
energy
Feed donates H+
H+s transferred to co-enzymes
NADH + H+ 3 ATP
FADH2 2 ATP
Electron Transport Chain
Total ATP from Glucose
Anaerobic glycolysis 2 ATP + 2 NADH
Aerobic metabolism glycolysis + TCA
31 ATP from 1 glucose molecule
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
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
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
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
A BRIEF INTERLUDE
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)
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
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
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
Glucose Utilization
Energy
Adipose Stores Glycogen
Glucose
Pentose Glycolysis
Phosphate
Pathway
Ribose-5-phosphate Pyruvate
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
Glucose Utilization
Energy
Adipose Stores Glycogen
Glucose
Pentose Glycolysis
Phosphate
Pathway
Ribose-5-phosphate Pyruvate
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 ATP:ADP ratios
High ATP, acetyl-CoA goes to fatty acid synthesis
Low ATP, acetyl CoA enters TCA cycle to generate
MORE ATP
Glucose Utilization
Energy
Adipose Stores Glycogen
Glycogenesis
Glucose
Pentose Glycolysis
Phosphate
Pathway
Ribose-5-phosphate Pyruvate
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
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
Fates of Glucose
Fed state Synthesis and
Storage as glycogen breakdown occur at
Liver
Skeletal muscle
all times
Storage as lipids regardless of state...
Adipose tissue
Fasted state The relative rates of
Metabolized for energy synthesis and
New glucose synthesized breakdown change
Fasting Situation in Non-Ruminants
Where does required glucose come from?
Glycogenolysis
Breakdown or mobilization of glycogen stored by glucagon
Glucagon - hormone secreted by pancreas during times of fasting
Lipolysis
Mobilization of fat stores stimulated by glucagon and epinephrine
Triglyceride = glycerol + 3 free fatty acids
Glycerol can be used as a glucose precursor
Proteolysis
The breakdown of muscle protein with release of amino acids
Alanine can be used as a glucose precursor
Low Blood Glucose
Pancreas
Insulin Glycogen
Muscle
Proteins Broken Down Glucose released
Adipose
Cells
Importance of gluconeogenesis
MOST monogastrics = less important
Ruminant = very important