Download Metabolism of Carbohydrates

Carbohydrate Metabolism
An Overview of Metabolism
Adenosine Tri-Phosphate (ATP)
Link between energy releasing and energy
requiring mechanisms


“rechargeable battery”
ADP + P + Energy
ATP
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
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
Anabolism




Performance of structural
maintenance and repairs
Support of growth
Production of secretions
Building of nutrient reserves
Catabolism

Breakdown of nutrients to provide
energy (in the form of ATP) for body
processes


Nutrients directly absorbed
Stored nutrients
Cells and Mitochondria


Cells provide small organic
molecules to mitochondria
Mitochondria produce ATP used
to perform cellular functions
Metabolism of Carbohydrates
Carbohydrate Metabolism
 Primarily

Fructose and galactose enter the pathways at various points
 All

glucose
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

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
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
High Blood Glucose
Pancreas
Insulin
Muscle
Glucose absorbed
Glycogen
Glucose absorbed
Adipose
Cells
Glucose absorbed
immediately after eating a meal…
Glucose Metabolism

Four major metabolic pathways:
 Immediate source of energy
 Pentophosphate pathway
 Glycogen synthesis in liver/muscle
 Precursor for triacylglycerol
synthesis
Energy status (ATP) of body regulates which
pathway gets energy
Same in ruminants and non-ruminants
Fate of Absorbed Glucose

1st Priority: glycogen storage

Stored in muscle and liver
nd
 2


Priority: provide energy
Oxidized to ATP
3rd Priority: stored as fat


Only excess glucose
Stored as triglycerides in adipose
Glucose Utilization
Adipose
Energy
Stores
Glycogen
Glucose
Pentose
Phosphate
Pathway
Ribose-5-phosphate
Glycolysis
Pyruvate
Glucose Utilization
Adipose
Energy
Stores
Glycogen
Glucose
Pentose
Phosphate
Pathway
Ribose-5-phosphate
Glycolysis
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
Traps glucose in cells (irreversible in muscle cells)
Glycolysis - Summary
Glucose (6C)
2 ATP
4 ADP
2 ADP
4 ATP
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)
(oxidized)
(reduced)
Anaerobic Metabolism of
Pyruvate
 ATP

Two ATPs (net) are produced during the
anaerobic breakdown of one glucose


yield
The 2 NADHs are used to reduce 2 pyruvate
to 2 lactate
Reaction is fast and doesn’t require oxygen
Pyruvate Metabolism - Anaerobic
Lactate Dehydrogenase
Pyruvate
Lactate
NADH
NAD+
 Lactate can be transported by blood to liver and
used in gluconeogenesis
Cori Cycle
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
Keto acid
to alanine and export to blood
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
Transport
Chain
TCA Cycle
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

Oxidize acetyl-CoA to CO2 and capture potential
energy as NADH (or FADH2) and some ATP
TCA Cycle - Summary
Acetyl CoA
3
NAD
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 H2’s to
oxygen, forming water
Oxidation and Electron Transport

Oxidation of nutrients releases stored
energy
Feed donates H+
+
H ’s transferred to co-enzymes

NAD+ + 2H+ + 2eFAD + 2H+ + 2e-
NADH + H+
FADH2
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
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 +
FADH2
+
H
3 ATP
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


Propionate


Energy source and for fatty acid synthesis
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


Propionic acid


Yields 10 ATP
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


Increase carbon to oxidize




Increased kidney size, glomerular filtration rate
Increased ability to deliver oxygen to tissues and get rid of carbon dioxide




Increased liver size and blood flow to liver
Increased ability to excrete waste products


Increased gut size relative to body size
Increased feed intake
Increased digestive enzyme production
Increased ability to process nutrients


Horses, dogs, dairy cattle, hummingbirds!
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


Glucose
Pyruvate
Lactate
Aerobic carbohydrate metabolism


Creatine + ATP
Anaerobic glycolysis


Phosphocreatine + ADP
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


CO2 and H2O
Glucose
Pyruvate
CO2 and H2O
Anaerobic glycolysis


Acetate
Aerobic carbohydrate metabolism


Fatty Acid
Glucose
Pyruvate
Lactate
Substrate-level phosphorylation

Phosphocreatine + ADP
Creatine + ATP
Glucose Utilization
Adipose
Energy
Stores
Glycogen
Glucose
Pentose
Phosphate
Pathway
Ribose-5-phosphate
Glycolysis
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
Adipose
Energy
Stores
Glycogen
Glucose
Pentose
Phosphate
Pathway
Ribose-5-phosphate
Glycolysis
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
Adipose
Energy
Stores
Glycogen
Glycogenesis
Glucose
Pentose
Phosphate
Pathway
Ribose-5-phosphate
Glycolysis
Pyruvate
Glycogenesis
 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

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
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
Fasting Situation in Non-Ruminants

Where does required glucose come from?

 Breakdown or mobilization of glycogen stored by glucagon
Glycogenolysis
 Glucagon - hormone secreted by pancreas during times of fasting
 Mobilization of fat stores stimulated by glucagon and epinephrine
Lipolysis
 Triglyceride = glycerol + 3 free fatty acids
 Glycerol can be used as a glucose precursor
 The breakdown of muscle protein with release of amino acids
Proteolysis
 Alanine can be used as a glucose precursor
Low Blood Glucose
Pancreas
Muscle
Insulin
Proteins Broken Down
Glycogen
Glucose released
Adipose
Cells
Glycerol, fatty acids released
In a fasted state, substrates for glucose synthesis
(gluconeogenesis) are released from “storage”…
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
Gluconeogenesis

Vital for certain animals

Ruminant species and other pre-gastric fermenters

Convert carbohydrate to VFA in rumen



Feline species



Little glucose absorbed from small intestine
VFA can not fuel CNS and RBC
Diet consists primarily of fat and protein
Little to no glucose absorbed
Glucose conservation and gluconeogenesis
are vital to survival
Gluconeogenesis
Synthesis of glucose from non-carbohydrate
precursors during fasting in monogastrics

 Glycerol
 Amino acids
 Lactate
 Pyruvate
 Propionate
Supply carbon skeleton
There is no glucose synthesis from fatty acids
Carbohydrate Comparison

Primary energy substrate
 MOST monogastrics = glucose
 Ruminant/pre-gastric fermenters = VFA

Primary substrate for fat synthesis
 MOST monogastrics = glucose
 Ruminant = acetate

Extent of glucose absorption from gut
 MOST monogastrics = extensive
 Ruminant = little to none
Carbohydrate Comparison

Cellular demand for glucose
 Nonruminant = high
 Ruminant = high

Importance of gluconeogenesis
 MOST monogastrics = less important
 Ruminant = very important