Carbohydrate Metabolism. An Overview of Metabolism.
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Transcript of Carbohydrate Metabolism. An Overview of Metabolism.
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 phosphorylationSubstrate transfers a phosphate group directlyRequires enzymes
Phosphocreatine + ADP Creatine + ATPOxidative phosphorylation
Method by which most ATP formedSmall carbon chains transfer hydrogens to
transporter (NAD or FADH) which enters the electron transport chain
Metabolism is all the chemical reactions that occur in an organism
Cellular metabolismCells 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
Performance of structural maintenance and repairs
Support of growth Production of secretionsBuilding of nutrient reserves
Anabolism
Breakdown of nutrients to provide energy (in the form of ATP) for body processesNutrients directly absorbedStored nutrients
Catabolism
Cells provide small organic molecules to mitochondria
Mitochondria produce ATP used to perform cellular functions
Cells and Mitochondria
Metabolism of Carbohydrates
Carbohydrate MetabolismPrimarily glucose
Fructose and galactose enter the pathways at various pointsAll 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 metabolismGlucose uptake independent of insulinThe only exporter of glucose
Blood Glucose HomeostasisSeveral 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 stateStorage as glycogen
LiverSkeletal muscle
Storage as lipidsAdipose tissue
Fasted stateMetabolized for energyNew glucose synthesized
Synthesis and breakdown occur at
all times regardless of state...
The relative rates of synthesis and
breakdown change
High Blood Glucose
Glucose absorbed
Insulin
Pancreas
Muscle
Adipose Cells
Glycogen
Glucose absorbed
Glucose absorbed
immediately after eating a meal…
Glucose MetabolismFour major metabolic pathways:
Energy status (ATP) of body regulates which pathway gets energySame in ruminants and non-ruminants
Immediate source of energy Pentophosphate pathway Glycogen synthesis in liver/muscle Precursor for triacylglycerol synthesis
Fate of Absorbed Glucose
1st Priority: glycogen storageStored in muscle and liver
2nd Priority: provide energyOxidized to ATP
3rd Priority: stored as fatOnly excess glucose Stored as triglycerides in adipose
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
GlycogenEnergy Stores
Pentose Phosphate Pathway
Glycolysis
Adipose
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
GlycogenEnergy Stores
Pentose Phosphate Pathway
Glycolysis
Adipose
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)
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 - SummaryGlucose (6C)
2 Pyruvate (3C)
2 ATP
2 ADP
4 ADP
4 ATP
2 NAD
2 NADH + H
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)
(oxidized) (reduced)
(oxidized)(reduced)
Anaerobic Metabolism of Pyruvate
ATP yieldTwo ATPs (net) are produced during the
anaerobic breakdown of one glucoseThe 2 NADHs are used to reduce 2 pyruvate
to 2 lactateReaction is fast and doesn’t require oxygen
Pyruvate Metabolism - Anaerobic
Pyruvate Lactate
NADH NAD+
Lactate Dehydrogenase
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 metabolismConvert to alanine and export to blood
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
Electron Transport Chain
TCA Cycle
Aerobic Conditions
PDH - SummaryPyruvate
Acetyl CoA
2 NAD
2 NADH + H
CO2
TCA Cycle
In aerobic conditions TCA cycle links pyruvate to oxidative phosphorylation
Occurs in mitochondriaGenerates 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
TCA Cycle - Summary
Acetyl CoA3 NAD
3 NADH + H
1 FAD
1 FADH2
1 ADP1 ATP
2 CO2
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
Oxidation and Electron Transport
Oxidation of nutrients releases stored energyFeed donates H+
H+’s transferred to co-enzymes
NAD+ + 2H+ + 2e- NADH + H+ FAD + 2H+ + 2e- 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 ETCTravel through complexes I – IV
H+ flow through ETC and eventually attach to O2 forming water
NADH + H+ 3 ATPFADH2 2 ATP
Electron Transport Chain
Total ATP from Glucose
Anaerobic glycolysis – 2 ATP + 2 NADHAerobic metabolism – glycolysis + TCA 31 ATP from 1 glucose molecule
Volatile Fatty AcidsProduced by bacteria in the fermentation of pyruvateThree major VFAs
AcetateEnergy source and for fatty acid synthesis
PropionateUsed to make glucose through gluconeogenesis
ButyrateEnergy source and for fatty acid synthesisSome 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 oxidizedAcetic acid
Yields 10 ATPPropionic acid
Yields 18 ATPButyric acid
Yields 27 ATPLittle butyrate enters blood
Utilization of VFA in Metabolism
Acetate Energy Carbon source for fatty acids
AdiposeMammary 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
PropionateIncreases blood glucoseStimulates release of insulin
ButyrateNot used for synthesis of glucoseStimulates release of insulinStimulates release of glucagon
Increases blood glucoseAcetate
Not used for synthesis of glucoseDoes not stimulate release of insulin
GlucoseStimulates 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 sizeIncreased feed intakeIncreased digestive enzyme production
Increased ability to process nutrientsIncreased liver size and blood flow to liver
Increased ability to excrete waste productsIncreased kidney size, glomerular filtration rate
Increased ability to deliver oxygen to tissues and get rid of carbon dioxideLung size and efficiency increasesHeart size increases and cardiac output increasesIncrease capillary density
Increased ability to oxidize small carbon chainsIncreased numbers of mitochondria in cellsLocate mitochondria closer to cell walls (oxygen is lipid-soluble)
HummingbirdsLung oxygen diffusing ability 8.5 times greater than
mammals of similar body sizeHeart is 2 times larger than predicted for body sizeCardiac output is 5 times the body mass per
minuteCapillary density up to 6 times greater than
expected
Rate of ATP Production(Fastest to Slowest)
Substrate-level phosphorylationPhosphocreatine + ADP Creatine + ATP
Anaerobic glycolysisGlucose Pyruvate Lactate
Aerobic carbohydrate metabolismGlucose Pyruvate CO2 and H2O
Aerobic lipid metabolismFatty Acid Acetate CO2 and H2O
Potential Amount of Energy Produced (Capacity for ATP Production)
Aerobic lipid metabolismFatty Acid Acetate CO2 and H2O
Aerobic carbohydrate metabolismGlucose Pyruvate CO2 and H2O
Anaerobic glycolysisGlucose Pyruvate Lactate
Substrate-level phosphorylationPhosphocreatine + ADP Creatine + ATP
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
GlycogenEnergy Stores
Pentose Phosphate Pathway
Glycolysis
Adipose
Pentose Phosphate Pathway
Secondary metabolism of glucoseProduces NADPH
Similar to NADHRequired for fatty acid synthesis
Generates essential pentosesRiboseUsed for synthesis of nucleic acids
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
GlycogenEnergy Stores
Pentose Phosphate Pathway
Glycolysis
Adipose
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 excessDetermined by ATP:ADP ratios
High ATP, acetyl-CoA goes to fatty acid synthesisLow ATP, acetyl CoA enters TCA cycle to generate
MORE ATP
Glucose Utilization
Glucose
PyruvateRibose-5-phosphate
GlycogenEnergy Stores
Pentose Phosphate Pathway
Glycolysis
Adipose
Glycogenesis
Liver7–10% of wet weightUse glycogen to export glucose to the
bloodstream when blood sugar is lowGlycogen stores are depleted after
approximately 24 hrs of fasting (in humans)De novo synthesis of glucose for glycogen
Glycogenesis
Glycogenesis
Skeletal muscle1% 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 stateStorage as glycogen
LiverSkeletal muscle
Storage as lipidsAdipose tissue
Fasted stateMetabolized for energyNew 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? 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
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”…
GluconeogenesisNecessary process
Glucose is an important fuelCentral nervous systemRed blood cells
Not simply a reversal of glycolysisInsulin and glucagon are primary
regulators
GluconeogenesisVital for certain animals
Ruminant species and other pre-gastric fermentersConvert carbohydrate to VFA in rumen
Little glucose absorbed from small intestineVFA can not fuel CNS and RBC
Feline speciesDiet consists primarily of fat and proteinLittle 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
There is no glucose synthesis from fatty acids
Supply carbon skeleton
Carbohydrate ComparisonPrimary 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
Carbohydrate ComparisonCellular demand for glucose
Importance of gluconeogenesis
Nonruminant = high Ruminant = high
MOST monogastrics = less important Ruminant = very important