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Carbohydrate Metabolism

An Overview of Metabolism

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 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

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 Adipose tissue

Storage as lipids

Synthesis and breakdown occur at all times regardless of state...


The relative rates of synthesis and breakdown change

Fasted state

Metabolized for energy New glucose synthesized

High Blood Glucose


Pancreas
Insulin: Glucagon

Muscle

Glycogen

Glucose absorbed
Adipose Cells Glucose absorbed

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 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

2nd Priority: provide energy

Oxidized to ATP
Only excess glucose Stored as triglycerides in adipose

3rd Priority: stored as fat

Glucose Utilization
Adipose
Energy Stores

Glycogen

Glucose
Pentose Phosphate Pathway Glycolysis

Ribose-5-phosphate

Pyruvate

Glucose Utilization
Adipose
Energy Stores

Glycogen

Glucose
Pentose Phosphate Pathway Glycolysis

Ribose-5-phosphate

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 Pyruvate
Acetyl-CoA (TCA cycle)

Glycolysis
Glucose + 2 ADP + 2 Pi 2 Lactate + 2 ATP + 2 H2O

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 Substrate transfers electrons to transporter which enters the electron transport chain

First Reaction of Glycolysis

Traps glucose in cells (irreversible in muscle cells) Hexokinase is used by most plants, animals, and microbes to phosphorylate glucose Glucokinase in hepatic tissue Cows do not have hexokinase

Glycolysis - Summary
Glucose
2 ATP 4 ADP 2 ADP 4 ATP 2 NAD 2 NADH + H

2 Pyruvate

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

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

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)

NADH + H+ COO C O CH3 Pyruvate


(oxidized)

NAD+ COO HC OH

Lactate dehydrogenase

CH3 Lactate
(reduced)

Anaerobic Metabolism of Pyruvate

ATP yield

Two ATPs (net) are produced in the anaerobic breakdown of one glucose

The 2 NADHs are used to reduce 2 pyruvate to 2 lactate

Reaction is fast and doesnt require oxygen

Pyruvate Metabolism Anaerobic


Lactate Dehydrogenase

Pyruvate
NADH NAD+

Lactate

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 to alanine and export to blood


Glutamate -Ketoglutarate COO HC Alanine amino transferase (AAT) NH3+ CH 3 Alanine

COO C O CH3 Pyruvate

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

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 released from feed Metabolizes carbohydrate, protein, and fat Strategy is to oxidize acetyl-CoA to CO2 and capture energy as NADH(FADH2) and ATP

TCA Cycle - Summary


Acetyl CoA

1 ATP 1 ADP

3 NAD 3 NADH + H

1 FAD 1 FADH2

Oxidative Phosphorylation

Oxidative Phosphorylation and the Electron Transport System

Requires coenzymes (NAD and FAD) as H+ carriers and consumes oxygen Key reactions take place in the electron transport system (ETS)

Cytochromes of the ETS pass H2s to oxygen, forming water

The basic chemical reaction is: 2 H2 + O2 2 H2O

Oxidation and Electron Transport

Oxidation of nutrients releases stored energy


Feed donates H+ H+s transferred to co-substrate NADH + H+ FADH2

NAD+ + 2H+ + 2eFAD + 2H+ + 2e-

So, What Goes to the ETS???


From each molecule of glucose entering glycolysis:
1. 2. 3. From glycolysis: 2 NADH From the TCA preparation step (pyruvate to acetyl-CoA): 2 NADH 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 3 ATP 2 ATP

NADH + H+ FADH2

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 Provides important energy sources for animals, particularly ruminants or those that rely on cellulose as a key carbohydrate in their diet Three major VFAs

Acetate

Propionate

Energy source and for fatty acid synthesis Used to make glucose through gluconeogenesis Energy source and for fatty acid synthesis Some use and metabolism (alterations) by rumen wall and liver before being available to other tissues

Butyrate

Use of VFA for Energy

Enter TCA cycle to be oxidized

Acetic acid

Yields 10 ATP Yields 18 ATP Yields 27 ATP Little butyrate enters blood

Propionic acid

Butyric acid

Utilization of VFA in Metabolism


Acetate
Energy Carbon source for fatty acids
Adipose Mammary gland

Not used for net synthesis of glucose

Propionate Butyrate
Energy Precursor of glucose
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

Oxidation and Electron Transport

Oxidation of nutrients releases stored energy


Feed donates H+ H+s transferred to co-substrate NADH + H+ FADH2

NAD+ + 2H+ + 2eFAD + 2H+ + 2e-

Oxidative Phosphorylation

A BRIEF INTERLUDE

Need More Energy (More ATP)??

Working animals

Increase carbon to oxidize


Horses, dogs, dairy cattle, hummingbirds! Increased gut size relative to body size Increased feed intake Increased digestive enzyme production Increased liver size and blood flow to liver

Increased ability to process nutrients

Increased ability to excrete waste products

Increased ability to deliver oxygen to tissues and get rid of carbon dioxide

Increased kidney size, glomerular filtration rate

Increased ability to oxidize small carbon chains


Lung size and efficiency increases Heart size increases and cardiac output increases Increase capillary density
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

Phosphocreatine + ADP Glucose Glucose Fatty Acid Pyruvate Pyruvate Acetate

Creatine + ATP Lactate CO2 and H2O CO2 and H2O

Anaerobic glycolysis

Aerobic carbohydrate metabolism

Aerobic lipid metabolism

Potential Amount of Energy Produced (Capacity for ATP Production)

Aerobic lipid metabolism

Aerobic carbohydrate metabolism

Fatty Acid
Glucose Glucose

Acetate

CO2 and H2O

Anaerobic glycolysis

Pyruvate Pyruvate

CO2 and H2O Lactate

Substrate-level phosphorylation

Phosphocreatine + ADP

Creatine + ATP

Glucose Utilization
Adipose
Energy Stores

Glycogen

Glucose
Pentose Phosphate Pathway Glycolysis

Ribose-5-phosphate

Pyruvate

Pentose Phosphate Pathway

Secondary metabolism of glucose

Produces NADPH

Similar to NADH Required for fatty acid synthesis Ribose Used for synthesis of nucleic acids

Generates essential pentoses


Pentose Phosphate Pathway


Glucose-6phosphate 6-Phosphogluconolactone 6-Phosphogluconate

D-Ribulose5-phosphate

RNA or DNA

D-Ribose5-phosphate

Glucose Utilization
Adipose
Energy Stores

Glycogen

Glucose
Pentose Phosphate Pathway Glycolysis

Ribose-5-phosphate

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 Glycolysis

Ribose-5-phosphate

Pyruvate

Glycogenesis

Liver

710% 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 Adipose tissue

Storage as lipids

Synthesis and breakdown occur at all times regardless of state...


The relative rates of synthesis and breakdown change

Fasted state

Metabolized for energy New glucose synthesized

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


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

Fasting Situation in Non-Ruminants

Where does required glucose come from?


Glycogenolysis
Breakdown or mobilization of glycogen stored by glucagon Glucagon - hormone secreted by pancreas during times of fasting

Lipolysis
Mobilization of fat stores stimulated by glucagon and epinephrine Triglyceride = glycerol + 3 free fatty acids Glycerol can be used as a glucose precursor

Proteolysis

The breakdown of muscle protein with release of amino acids Alanine can be used as a glucose precursor

Low Blood Glucose


Pancreas
Insulin: Glucagon

Muscle
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

Synthesis of glucose from non-carbohydrate precursors during fasting in monogastrics


Glycerol Amino acids Lactate Supply carbon skeleton Pyruvate Propionate There is no glucose synthesis from fatty acids

Occurs primarily in liver, but can also occur in kidneys and small intestine

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 MOST monogastrics = abnormal situation Ruminant = normal situation

Ketone production

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