Carbohydrate metabolism involves the breakdown of glucose and other carbohydrates to produce energy in the form of ATP. Glucose is either stored as glycogen, metabolized through glycolysis to produce energy, or stored as fat. Pyruvate produced through glycolysis can be converted to lactate through anaerobic metabolism or enter the mitochondria to undergo aerobic metabolism through the TCA cycle and oxidative phosphorylation, producing the most ATP. Volatile fatty acids produced by gut bacteria are also metabolized through these pathways to produce energy. Organisms with high energy demands increase various physiological capacities to produce ATP through carbohydrate and lipid metabolism.

1. Carbohydrate Metabolism

2. An Overview of Metabolism

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

9. Metabolism of Carbohydrates

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

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

17. Glucose Utilization
Glucose
Pyruvate
Ribose-5-phosphate
Glycogen
Energy
Stores
Pentose
Phosphate
Pathway
Glycolysis
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)

19. Glycolysis
Glucose + 2 ADP + 2 Pi
2 Pyruvate + 2 ATP + 2 H2O

20. First Reaction of Glycolysis
Traps glucose in cells (irreversible in muscle cells)

21. Glycolysis - Summary
Glucose (6C)
2 Pyruvate (3C)
2 ATP
2 ADP
4 ADP
4 ATP
2
NAD
2 NADH + H

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
Lactate
Pyruvate
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

27. Pyruvate Metabolism -
Anaerobic
Pyruvate Lactate
NADH NAD+
Lactate Dehydrogenase
 Lactate can be transported by blood to liver and
used in gluconeogenesis

28. Cori Cycle
Lactate is converted to
pyruvate in the liver

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
C
O
O–
C O
C
H3
C
O
O–
H
C N
H3
+
C
H3
A
lan
in
eam
in
otran
sferase
(A
A
T
)
A
lan
in
e
Py
ru
vate
G
lu
tam
ate α-K
etog
lu
tarate
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

32. Pyruvate Dehydrogenase
Complex (PDH)
 Prepares pyruvate to enter the TCA cycle
Electron
Transport
Chain
TCA
Cycle
Aerobic Conditions

33. PDH - Summary
Pyruvate
Acetyl CoA
2
NAD
2 NADH + H
CO2

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

36. TCA Cycle -
Summary
Acetyl CoA
3
NAD
3 NADH + H
1 FAD
1 FADH2
1 ADP
1 ATP
2 CO2

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

41. Electron Transport Chain

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

47. A BRIEF INTERLUDE…

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

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

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

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

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

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

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