3. Adenosine Tri-Phosphate (ATP)
Link between energy releasing and
energy requiring mechanisms
“rechargeable battery”
ADP + P + Energy ATP
4. 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
5. 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
Metabolism
6. Performance of structural
maintenance and repairs
Support of growth
Production of secretions
Building of nutrient reserves
Anabolism
7. Breakdown of nutrients to provide
energy (in the form of ATP) for body
processes
Nutrients directly absorbed
Stored nutrients
Catabolism
8. Cells provide small organic
molecules to mitochondria
Mitochondria produce ATP used
to perform cellular functions
Cells and Mitochondria
10. 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
11. 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
12. 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
Synthesis and
breakdown occur at
all times
regardless of state...
The relative rates of
synthesis and
breakdown change
13. High Blood Glucose
Glucose absorbed
Insulin
Pancreas
Muscle
Adipose
Cells
Glycogen
Glucose absorbed
Glucose absorbed
immediately after eating a meal…
14. 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
15. 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
18. Glycolysis
Sequence of reactions that converts
glucose into pyruvate
Relatively small amount of energy produced
Glycolysis reactions occur in cytoplasm
Does not require oxygen
Glucose → 2 Pyruvate
Lactate (anaerobic)
Acetyl-CoA (TCA cycle)
22. 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)
23. Pyruvate Metabolism
Three fates of pyruvate:
Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway
24. 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…
25. Anaerobic Metabolism
of Pyruvate
Solution:
Turn NADH back to NAD+
by making lactate (lactic acid)
COO–
C O
CH3
COO–
HC OH
CH3
LactatePyruvate
Lactate dehydrogenase
NADH+H+
NAD+
(oxidized) (reduced)
(oxidized)(reduced)
26. 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 doesn’t require oxygen
29. Pyruvate Metabolism
Three fates of pyruvate:
Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway
30. Pyruvate metabolism
Convert to alanine and export to blood
COO–
C O
CH3
COO–
HC NH3
+
CH3
Alanineaminotransferase
(AAT)
AlaninePyruvate
Glutamate α-Ketoglutarate
Keto acid Amino acid
31. Pyruvate Metabolism
Three fates of pyruvate:
Conversion to lactate (anaerobic)
Conversion to alanine (amino acid)
Entry into the TCA cycle via pyruvate
dehydrogenase pathway
34. 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
37. 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 H2’s to
oxygen, forming water
Oxidative Phosphorylation and
the Electron Transport System
38. Oxidation and Electron
Transport
Oxidation of nutrients releases stored
energy
Feed donates H+
H+
’s transferred to co-enzymes
NAD+
+ 2H+
+ 2e-
NADH + H+
FAD + 2H+
+ 2e-
FADH2
39. So, What Goes to the ETS???
From each molecule of glucose entering glycolysis:
1. From glycolysis: 2 NADH
2. From the TCA preparation step (pyruvate to acetyl-CoA): 2 NADH
3. From TCA cycle (TCA) : 6 NADH and 2 FADH2
TOTAL: 10 NADH + 2 FADH2
40. 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
42. Total ATP from Glucose
Anaerobic glycolysis – 2 ATP + 2 NADH
Aerobic metabolism – glycolysis + TCA
31 ATP from 1 glucose molecule
43. 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
44. 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
45. 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
46. 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
48. 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)
49. 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
50. 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
51. 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
53. 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
55. 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
57. Liver
7–10% 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
Glycogenesi
s
58. 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
59. 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
Synthesis and
breakdown occur at
all times
regardless of state...
The relative rates of
synthesis and
breakdown change
60. 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
61. Low Blood Glucose
Proteins Broken Down
Insulin
Pancreas
Muscle
Adipose
Cells
Glycogen
Glycerol, fatty acids released
Glucose released
In a fasted state, substrates for glucose
synthesis (gluconeogenesis) are released from
“storage”…
62. 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
63. 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
64. 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
65. 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
66. Carbohydrate Comparison
Cellular demand for glucose
Importance of gluconeogenesis
Nonruminant = high
Ruminant = high
MOST monogastrics = less important
Ruminant = very important