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




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


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



Pyruvate metabolismConvert to alanine and export to blood

Keto acid Amino acid

Pyruvate Metabolism



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


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


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




Glycolysis

Adipose


Secondary metabolism of glucoseProduces NADPH

Similar to NADHRequired for fatty acid synthesis

Generates essential pentosesRiboseUsed for synthesis of nucleic acids

Glucose Utilization

Glucose




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




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

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Carbohydrate Metabolism. An Overview of Metabolism