Classes and functions of macro-

nutrients
Dr Hadeel Ali Ghazzawi
2018/2019
Nutrition Department

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Refreshing your biochemistry information

• Glycolysis
• Glycogenesis
• Gluconeogenesis
• Citric acid cycle
• Respiratory chain
• Cori cycle (lactic acid cycle)

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 Glycolysis
• The breaking down of glucose into pyruvic or
lactic acid
– Anaerobic  lactic acid
– Aerobic pyruvate

3
 Glycogenesis
• The breaking down of glycogen into glucose
and its metabolites

4
 Gluconeogenesis
• The synthesis of glucose and stored it as
glycogen from non-carbohydrate source
(lactate, glycerol, amino acids…)

5
 Citric acid cycle
• The process whereby CHO, protein and fat are
completely oxidized to CO2, water and energy.

6
 Respiratory chain
• Electron transport system.
• The system of hydrogen atoms from biological
oxidation for acceptance by oxygen atoms to
form water molecule.

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 Cori cycle (lactic acid cycle)
• Refers to the metabolic pathway in which
lactate produced by muscle during anaerobic
glycolysis.
• The lactate is released to the blood,
taken up by the liver
and is converted back to glucose,
which is released again to be used
by muscle
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• Carbohydrates
• Proteins
• Fats
• Vitamins
• Minerals
• Water

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CARBOHYDRATES

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 Aspects to be considered
• Controversy exists concerning the potential
effects of high-carbohydrate diets on
increased risk for obesity, diabetes, CHD esp
among sedentary and obese adults and
children.
• The more fiber rich food the less rate of DB
coincidence.

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 Not all carbs are physiologically equal
• Digestion rates of different carbs sources
explain the link between CHO intake and DB
and excess body fat.
• Fiber rich food slow carbs digestion
minimizing sugars in blood glucose.
• Low fiber processed starches (& simple sugars
in soft drinks)  digest quickly & have high
glycemic index& high glycemic load
• Glycemic index
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 A role in obesity
• Insulin resistance face weight gain risk esp
when consume high GI index food.
• Because excessive insulin
– facilitate glucose oxidation rather than FA
oxidation
– Stimulate VLDL synthesize by liver
– Stimulate fat storage in adipose tissue.

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 Strategy to reduce type 2 DB and obesity
risk
• Consume carbohydrate foods that are:
– More slowly absorbed
– Unrefined complex CHO
– Low GI
• These foods provide slow release CHO
without triggering rapid fluctuations in blood
sugar.
• 8 to 10 g per kg of body mass

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 Intake recommendation
• For sedentary 70-kg person  40-50% ~ 300g
• For more PA people and who involved in
exercise training 60% ~ 400-600 g
– Mostly fiber rich fruits,
– Grains
– Unrefined
– Veg
• Intense training 70% ~ 8-10 g/kg body mass

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Carbohydrate dynamic in exercise
• Exercise fuel mixer is determined by
– The effort and the fitness
• The intensity
• The duration
• Nutritional status of the exerciser

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• The liver increases glucose release to active
muscle as exercise progresses from low to
high intensity.
• Muscle glycogen supplies the predominant
carbs energy source during the early stages of
exercise and as intensity increases.

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 Preferable fuel
• During aerobic exercise
– Carbs remains the preferable fuel compared with
fat and protein!!!
– Why !!!!
• It rapidly supplies energy (ATP) via oxidative processes.
• During anaerobic exercise (requiring glycolysis
reaction)
– Carbs becomes the SOLE macronutrient
contributor of ATP.
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 Anaerobic
• Increased level of ATP, PCr, free creatine and
glycogen
• Improvement of muscular strength.
• Increased quantity and activity of key enzymes
that control the anaerobic phase of glucose
catabolism specially in fast twitch muscle fiber.
• Greater portion of the muscles’ cross sectional
area.

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• Increased capacity to tolerate high levels of
blood lactate:
– Increased level of glycogen and glycolytic
enzymes.
– Improved motivation and pain tolerance.

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 Aerobic exercise
• Muscle fiber contain more and larger
mitochondria.
• Increased in aerobic system enzymes within 5-
10 days of training.
• Enhanced fat catabolism (lipolysis).
• Greater blood flow within trained muscle.
• Long term aerobic exercise improves the
elasticity of blood vessels (ability of the vessels
to expand and contract).
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 CHO and activity type
• At rest and during exercise:
– Liver glycogenoloysis maintains normal blood
glucose
• In prolonged, heavy exercise:
– Glucose level falls below normal as the liver
glycogen depleted and the active muscle continue
to use the available glucose.

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• Sustained and profound hypoglycemia can
lead to irreversible brain damage.

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• Carbohydrate availably in the metabolic
mixture control its use for energy.
• Carbs intake affects its availability.
• Blood glucose [] regulate liver’s glucose
output:
– High blood glucose inhibit hepatic glucose
release during exercise

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• Carbohydrate availably during exercise
regulate fat mobilization and its use for
energy.

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• Increasing CHO oxidization by ingesting high GI
prior to exercise inhibits 2 processes:
– LCFA oxidation by skeletal muscle.
– FFA liberation from adipose tissue.
• Adequate CHO availability inhibits transport
LCFA into the mitochondria.

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 Intense exercise
• During strenuous exercise Neural-humoral factors :
– increase the output of:
• Epinephrine
• Norepinephrine
• Glucagon
– Decrease
• Insulin release.
• Those hormones activate glycogen phosphorylase
(Facilitates glycogenolysis in the liver and activate muscle)
• "all your muscles need more oxygen during strenuous
exercise”
• the more strenuous the exercise, the faster your heart will
beat. 30
• Because muscle glycogen provides energy
without oxygen; it contributes the most
energy in the early minutes of exercise when
oxygen use does not meet oxygen demands.
• As exercise continue, blood glucose may
supply up to 30% of the total energy required.

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• An hour of high-intensity exercise decreases
liver glycogen by 55%
• 2 hour of strenuous workout almost depletes
glycogen in the liver and specifically exercised
muscles.

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 Moderate and prolonged exercise
• Glycogen stored in active muscle supplies
almost all of the energy in the transition from
rest to moderate exercise.
• During the next 20 minutes or so; liver
glycogen supply 40 -50 % of the energy
requirement,
– the remainder is provided by fat catabolism and
limiting amount of protein.

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• The nutrient mixture for energy depend on
the relative intensity of exercise.
– Light exercise fat remains the main energy
substrate.
– As exercise continues and muscle glycogen stores
decreases, blood glucose from dietary CHO
becomes the major supplier.
– If continue without Dietary CHO fat catabolism
will supply a great % of total energy.
– Hypoglycemia eventually.

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• Submaximal exercise progresses in the
glycogen-depleted state
– Blood glucose levels fall and circulating fat (FFA)
increases dramatically.
• Submaximal exercise progresses in the
glycogen-loaded state
– Blood glucose levels stay high and FFAs are not
consumed.

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 Hitting the wall\ bonking
• Fatigue occurs when exercise continues to the
point that compromises liver and muscle
glycogen supply.
• The depletion of glycogen stores in the liver
and muscles, which manifests itself by sudden
fatigue and loss of energy.
• What remains unclear is why muscle glycogen
depletion coincidences with the point of
fatigue !!!
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• brief rest and the ingestion of food or drinks
containing carbs can sort out this condition.
• The condition can usually be avoided by
ensuring that
– glycogen levels are high when the exercise
begins,
– maintaining glucose levels during exercise
by
• eating or drinking carbohydrate-rich
substances,
• or by reducing exercise intensity.
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 Summary
• Carbs stored in limited amount in liver and
muscle.
• Glycogen has 4 important functions:
– Provide a major source of energy.
– Spares protein breakdown.
– Functions as a metabolic primer for fat catabolism,
– Provides the fuel for CNS.

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• Muscle glycogen provides the primary energy
substrate (fuel) during intense anaerobic
exercise.
• Fat contributes about 50% of the energy
requirement during light and moderate
exercise.

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• Stored intramuscular fat and fat derived from
adipocytes becomes important during
prolonged exercise.
• In this situation, the fatty acid molecules
(circulatory FFAs) supply more than 80% of the
exercise energy requirements.

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LIPIDS

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• Triacylglycerol a more preferred term than
triglycerides among biochemists because it
describes glycerol acylated by 3 FAs.
• The major storage form of fat in fat cells
(adipocytes) are triglycerides.
Only FFAs are used to form ATP
• Other types of fat serve non-energy-producing
function.

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 Triacylglycerol formation
• Esterification: 3 FAs attached to CoA then
transfer to glycerol.
• TG synthesis increases following a meal:
1. Due to increased blood levels of FAs and glucose
from food absorption.
2. And high level of circulating insulin which
facilitate TG synthesis.

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 Triacylglycerol breakdown
• Lipolysis: catabolism of TG to yield glycerol and
the energy-rich FAs.
• Rate of fat supply is slower than CHO
• The mobilization of fatty acids via lipolysis
predominates due to:
1. Low-to-moderate exercise.
2. Low-calorie dieting or fasting
3. Cold stress
4. Prolonged exercise that depletes glycogen
reserves. 44
 Lipolysis
• Begins with the breakdown of the triglycerols
to FFA and glycerol.
• Catabolism of FAA involves their transport into
the mitochondria where they are catabolized
by β-oxidation.
• Fatty acids are activated by fatty acyl CoA
synthetase which cost 2 ATP.
• FAA are released into the bloodstream and
circulate throughout the body.
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 β- oxidation
• the catabolic process by which fatty acid
molecules are broken down in the cytosol in
the mitochondria to generate acetyl-CoA.
• Number of steps depends on the number of
carbons in the FFA, which submit how many
acetyl CoA is produced in beta oxidation

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• Palmitic acid (16 carbons): 16 carbons/2 =
8 Acetyl CoA.
• The end product of each cycle is the fatty acid
shortened by 2 carbons and acetyl CoA.
• The acyl units become acetyl CoA which then
enters the Krebs cycle for the formation of
ATP.

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 Carnitine shuttles
• Fatty acids are oxidized in mitochondria, and
synthesized in the cytoplasm.
• LCFA must form an active intermediate, fatty
acyl-CoA, before being oxidized inside
mitochondria.
• Carnitine shuttles long-chain fatty acids across
mitochondrial membranes.
• Fatty acids are both synthesized from and
oxidized to a common compound, acetyl-CoA.
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• Important enzymes in mitochondrial membranes
that help prepare LCFAs for mitochondrial β-
oxidation include:
– acyl-CoA synthetase,
– carnitine palmitoyltransferase I (CPT-1),
– carnitine-acylcarnitine translocase (CAT),
– and carnitine palmitoyltransferase II (CPT-2).
• Peroxisomal β-oxidation is reserved for VLCFA (C20 or
longer), that are poorly handled by mitochondria.
• Oxidation is uncoupled from phosphorylation in
peroxisomes.
• Cytoplasmic malonyl-CoA inhibits the rate-limiting
enzyme in fatty acid oxidation.
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Recommended dietary lipid intake
• No firm standards for optimal lipid intake
exist.
• Replace high fat foods with fruits, veg, whole
grains, fat free and low fat dairy products, fish,
poultry, and lean meat.
• Two weekly servings of fish high in n-3 FA.
• Cholesterol to be less than 100mg per 1000
calories consumed.

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 Role of lipids in the body
• Important functions:
1. Energy source and reserve
2. Protection of vital organs
3. Thermal insulation
4. Vitamins carrier and hunger suppressor.

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• Fat provides as much as 80 to 90% of the
energy requirement of a well-nourished
individual at rest.
• Fat exists as
– a relatively water-free, concentrated fuel,
• whereas glycogen remains
– hydrated and heavy relative to its energy content.

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• Fat synthesizing produce 3 water molecules
while each gram of glycogen store 2.7 g of
water.
• Fat used as a fuel also spares protein to carry
out its important functions of tissue synthesis
and repair.

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• Phospholipids:
– Key structural component of all cell membranes
and form protective sheath around some large
nerves.
• Steroids:
– Found in cells membranes and also function as
hormones or as building blocks of hormones such
estrogen and testerone.

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 Fat dynamics in exercise
• Intracellular and extracellular fat supply
between 30 and 80% of the energy for PA
depending on
– nutritional and fitness status
– exercise intensity and duration

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• Increased blood flow through adipose tissue
with exercise increases the release of FFAs for
delivery to and use by muscle.
• The quantity of fat used for energy in light and
moderate exercise is 3 times that used in
resting condition.

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• With more intense exercise; adipose tissue
release of FFAs fails to increase much above
the resting levels leads to a decrease in
plasma FFAs.
• This in turn stimulates the using of muscle
glycogen and concurrently the oxidation of the
IMTG.

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IMTG

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Adipose tissue

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• The start of exercise produces an initial drop in
plasma FFAs [] as active muscles increase the
uptake of FFAs.
• An increased of FFAs release from adipose
tissue and a suppression of TG formation due
to:
– Hormonal stimulation by sympathetic NS
– A decrease on plasma insulin levels.

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• During moderate exercise; equal amounts of
fat and CHO supply energy.
• When exercise continue for an hour or more,
fat catabolism gradually supplies a greater %
of energy with the progression of glycogen
depletion.

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• Toward the end of the prolonged exercise,
when glycogen reserves become nearly
depleted, fat supplies up to 80% of the total
energy requirement.

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 Summary
• Fat contribute 50 to 70% of the energy
requirement during light and moderate
exercise.
• Stored fat (intramuscular and derived from
adipocytes) plays an increasingly important
role during prolonged exercise.
• Fatty acid molecules (mainly circulating FFAs)
provide more than 80% of the exercise energy
requirements.
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• Aerobic training increases LCFA oxidation,
primarily FAs from TG within active muscle,
during mild- to moderate- intensity exercise.
• Enhanced fat oxidation with training spares
glycogen; this allows the trainer to exercise
more without experience the fatiguing effects
of glycogen depletion.

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• Oxygen delivery is limited by the oxygen
transport system so CHO is the preferred fuel
during high intensity exercise.
• During the light to moderate activity, the cost
of ATP can be tolerated.

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• As intensity increases (stimulation of glycolysis
and glycogenoloysis), the relative contribution
of FFA catabolism decreases with complete
dependence on CHO catabolism occurring at
intensities above 60-85% VO2 max.

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• When blood glucose is low and liver glycogen
is low minimal G6P is produced and
metabolized in glycolysis.
• (resulting in the creation of a phosphate group
and free glucose. Glucose is then exported
from the cell via glucose transporter
membrane proteins.)
• FFA catabolism predominates via β- oxidation

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• Mitochondrial oxaloacetate concentration
decrease which limit the entry of acetyl CoA
into TCA cycle.
• Ketone bodies (in the liver), in case of
starvation, DM & prolonged exercise.

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PROTEIN

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• An average size adult contain between 10 and
12 kg of protein with the largest quantity (6 to
8 kg) located in skeletal muscle.
• AAs not used to synthesize protein or other
compounds, or for energy metabolism provide
substrate for gluconeogenesis or convert to TG
for storage in adipocytes.

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 Recommended intake
• Despite the beliefs of many coaches, trainers,
and athletes, little benefit rewards from
consuming excessive protein.
• Muscle mass does not increase simply by
eating high-protein foods.
• Excessive dietary protein intake above
recommended values can trigger harmful side
effects.

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 Role of the protein in the body
• No reservoirs of this macronutrient exist.
• All protein contributes to tissue structures or
body systems (metabolic, transport, and
hormonal).
• AAs provides the major building blocks for
synthesizing tissue.

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 Dynamics of protein metabolism
• Dietary protein’s main contribution is
supplying amino acids to numerous anabolic
processes.
• Some protein is catabolized for energy.
• Only amino acid can be used for energy.
• In well-nourished person at rest, protein
catabolism contributes between 2 to 5 % of
the body’s total energy requirements.

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Protein dynamics in exercise and training

• Protein breakdown (deamination) yield urea

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• Increases in protein catabolism during
endurance and intense training often reflect
the metabolic mixture in acute starvation.
• With depleted glycogen reserves,
gluconeogenesis from AAs carbon largely
sustains the liver’s glucose output.
• More protein breakdown to maintain the
blood glucose for CNS functioning
(gluconeogenesis).
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• Athletes should consume a high- CHO diet
with adequate energy to conserve muscle
protein.

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Controlling the rate of energy production

• The energy rate is primarily determined by

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 Amino acid oxidation
• Protein can be catabolized to AA and then
have the nitrogenous amino group removed
(deamination) with the carbon skeleton
incorporated into the central pathways of CHO
and lipid metabolism.

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 Amino acid catabolism
• Measurement of protein oxidation is more
complex because AA’s contain nitrogen which
cannot be oxidized.
• Protein contributes relatively little to energy
production < 5% to 10%> therefore it’s
metabolism is often considered negligible.

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 Summary
• Physically active people and competitive
athletes usually obtain their nutrient needs
form balanced diet intake.
• Depleting CHO reserves significantly increase
protein catabolism during exercise.
• Athletes must maintain optimal levels of
muscle and liver glycogen to minimize
deterioration in performance.

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• Go and read about

the Alanine- Glucose Cycle.

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 Catabolism in liver
• It can catabolize CHO, protein and fatty acids.
• Liver is responsible for regulation of blood
glucose and lipoprotein.
• Liver doesn’t experience the large increase in
ATP demands as in muscle.
• There are differences in regulation of certain
enzymes and in the presence of certain
enzymes as well.

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The Three Metabolic Energy Systems
ATP GENERATION/ RESYNTHESIZE

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 Catabolism
• The main tissues that influence energy
metabolism during exercise are:
– Skeletal muscle
– Liver
– Adipose tissue

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• These tissues support the metabolic function
of one another to ensure adequate availability
of energy substrate.
• The basic energy system:
– Cells can store only very limited amounts of ATP
and must constantly generate new ATP.

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 ATP generation
• Cells generate ATP through any one of (or
combination of) 3 metabolic pathways:
Anaerobic – The ATP-PCr system
– The glycolytic system (glycolysis)
Aerobic – The oxidative system (oxidative phophorylation)

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 Catabolism in skeletal muscle
• The main catabolic pathways of skeletal
muscle are:
– The phosphagen system
– Glycogenoloysis
– Glycolysis
– Lipolysis
– Β-oxidation cellular respiration.

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 The Three Metabolic Energy Systems

1. The phosphagen system

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 1. The phosphagen system
• Phosphagen are energy storage compounds, also
known as high-energy phosphate compounds,
mainly found in muscular tissue in animals.
• ATP-PCr system:
– The creatine phosphate ( CrP) reaction is the most
rapid in means to regenerate ATP.
– provides muscle with a reservoir of 'high-
energy' phosphate for the rapid rephosphorylation of
ADP to ATP during high-intensity exercise.
– Also known as phosphocreatine (PCr).
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 Creatine
• Naturally-occurring amino acid (protein
building block) that's found in meat and fish,
• Made by the human body in the liver, kidneys,
and pancreas.
• It is converted into creatine phosphate or
phosphocreatine and stored in the muscles,
where it is used for energy.

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• The phosphagen system is crucial to the
muscle’s ability to tolerate increases in
metabolic demands.
• This energy system provides immediate
energy through the breakdown of these
stored high energy phosphates.
• ATP yield by the CrP is depleted in 10 sec
during intense exercise.

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2. The glycolytic system (glycolysis)
• Anaerobic glycolytic system.
• Initially stored glycogen is converted to
glucose.
• Glucose is then broken down by a series of
enzymes.
• 2 ATP are used to fuel glycolysis and 4 are
created so the body gains 2 ATP to use for
muscular contraction.

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• is only an effective means of energy
production during short, intense exercise.
• providing energy for a period ranging from 10
seconds to 2 minutes.
• dominant from about 10–30 seconds during a
maximal effort.

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• Glycolysis is the major pathway of glucose
metabolism and occurs in the cytosol of all
cells.
• Phosphorylase is the main enzyme that is
responsible for catabolizing glucose risdue
from glycogen chain.
• This enzyme is activated by the increase of the
cAMP (Cyclic adenosine monophosphate),
which is produced in response to epinephrine.
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 Glycolysis
• Begins either with glycogenoloysis or the entry
of glucose into skeletal muscle.
• The entry of glucose from blood is facilitated
by the protein transporter GlUT4 (is the insulin-
regulated glucose transporter found primarily in
adipose tissues and striated muscle (skeletal and
cardiac) , which are increased in response to
insulin or intense exercise.

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 The first phase of glycolysis
• Involve the addition of phosphate to glucose
and conversion of phosphorylated glucose into
fructose structure.
• This phase requires the expense of 1 or 2 ATP
molecules.
• The main regulated enzymes are the
hexokinase & PFK (Phosphofructokinase).

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 The second phase of glycolysis
• Produces ATP, pyruvate and electron e- and
hydrogen ions H+ .
• the electrons and H+ are added to NAD+
forming NADH.
• the ratio of NAD+ to NADH is called the Redox
Potential, and it is important that the
cytostolic potential be maintained during
exercise to continue glycolysis.

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• Pyruvate is the final product of glycolysis and
– can be reduced to lactate in the cytosol
– or be transported into the mitochondria and
oxidized to Acytl-CoA.

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 Lactate production
• When pyruvate production exceeds the
pyruvate enter in the TCA (Krebs cycle), lactate
is produced.
• It’s production is associated with the release
of H+
• During high intensity exercise, the liberation of
H+ exceeds the buffering capacity of the cell
and lead to acidosis.

102
• This drop in cellular PH afects many of the
enzymes involved in energy production and
muscle contraction.

ONLY IN HIGH INTENSITY

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• Therefore muscle fatigue and pain observed
during high intensity exercise is due to the
associated drop in PH rather than lactate
itself.

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• Under steady state conditions: the majority of
pyruvate is not converted to lactate but enters
into the mitochondria where it is converted to
Acetyl-CoA.
• Lactate is not detrimental to muscle
metabolism but has a direct detrimental effect
on muscle performance.

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• It involves the regeneration of NAD+ thus helps
maintain the cytosolic redox potential and
continued glycolysis (ATP generation).

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 Mitochondrial respiration
• Mitochondrial contain the enzyme for the
reaction responsible for the utilization of
oxygen.
• During the entry of pyruvate into the
mitochondria it is converted to Acetyl-CoA and
NADH.

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• Acetyl-CoA formed from either CHO or lipids
catabolism then enters the catabolism
pathway called TCA (tricarboxylic acid) Krebs
cycle.
• The combined products of the TCA cycle are:
– ATP
– NADH
– FADH
– CO2
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 3. Oxidative phosphorylation
• Aerobic system
• metabolic pathway in which cells use enzymes
to oxidize nutrients, thereby releasing energy
which is used to reform ATP.
• transfer electrons from NADH and FADH2 and
use them to power ATP production

109
• The biochemical use of O2 occurs in the ETC
(electron transport chain) when proton and
electrons acquired in NADH and FADH are
used to add electrons to H+ atoms and O2 to
form water and ATP.
• This process is called oxidative
phosphorylation.

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• glycolysis and the subsequent step, the citric-
acid cycle, produce two easily oxidized
molecules: NADH and FADH.
• These redox molecules are used in an
oxidative-phosphorylation process to produce
the majority of the ATP that the body uses.

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Have an active weekend 

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