Keto Info Week 6/11

[spEEdfrEEk]

CATEGORY: biology/metabolism

TECHNICAL: ****

SUMMARY:

This is a fairly technical document that describes the

different types of fuel the body will use under variable exercise

conditions. Some of you out there, with a background in medicine,

will probably really enjoy the detail -- for others it's a pretty

hard read. As a result, I'm going to summarize some of the more

important (and interesting) points.

* ATP is the body's only energy source, everything is converted

into ATP at some point

* the order of fuels used by the body under intense exercise

conditions is: ATP first, CP second, muscle glycogen, blood

glucose, and liver glycogen. (glucose and glycogen are the

body's sugar reserves). If all of those resources are

exhausted, amino acids (proteins) are then converted to glucose

* "feeling the burn" in a particular muscle implies that the

glucose or stored glycogen are being metabolized at a rate

too fast for the amount of oxygen present. This leads to

lactic acid (causing the burn) which can be carried back to

the liver where it can be re-converted into glucose.

(so it's sort of a self feeding cycle)

* carbohydrate loading can, in general, double the amount of

glycogen stored in the muscle and liver. (and hence improve

your stamina and performance)

* adrenaline and noradrenaline are mostly responsible for the

release of stored glycogen from the liver, and stored free fatty

acids from adipose. Hence, without these two, you won't

be able to tap your body fat for fuel. Fortunately, exercise

increases both of them.

* the body stores fats inside active muscle cells too. This

intra-muscular triglyceride can also be tapped as an energy

source, but they are hit less and less as the intensity

and duration of an exercise increases.

* Proteins and ketones can be used as exercise substrate (fuel)

as well, but they only account for a small percentage, and

aren't very efficient at the task.

* Fats and triglycerides compose a significantly larger percentage

of your body's stored energy reserves. ATP/CP can only last

for a few seconds, and glucose/glycogen reserves can be

depeleted in only a few hours with the right kind of effort.

-------------------------------------------------------------

Basic Exercise Fuel Metabolism (1,2,3)

Introduction

The energy to fuel exercise can be generated from many different

sources. Which source provides the majority of energy during exercise is

dependent on a host of factors (such as availability, intensity/duration

of exercise, etc) all of which will be discussed in later sections. To

provide adequate background for upcoming sections, it will be helpful to

discuss the basics of energy generation first as well as the basic

pathways of fuel utilization during exercise.

ATP: the master chemical

ATP is the only substrate which the body can use for the

generation of energy. Hence, all energy generating pathways have as

their ultimate goal the generation of ATP. When a muscle contracts, ATP

provides energy by being broken down to Adenosine Diphosphate (ADP) in

the following reaction with the help of an enzyme called an ATPase.

ATPase

ATP ------------> ADP + Pi + energy (Note: Pi represents an inorganic

phosphate molecule)

Within each muscle, there is about 6 seconds worth of ATP stored

which can be used for immediate energy. So for activity to continue past

6 seconds, ATP must be generated through various other reactions. The

first of these of these is through what is called the creatine phosphate

(CP) system.

The creatine phosphate system

Also stored in the muscle is a substance called Creatine

Phosphate (CP). This provides a phosphate molecule to ADP to regenerate

ATP so that muscular activity can continue. CP donates it's high energy

Phosphate molecule to ADP to regenerate ATP via an enzyme called creatine

kinase in the following reaction.

Creatine

ADP + CP --------------> ATP + Creatine

Kinase

There is enough stored CP in a normal muscle to provide energy

for approximately the first 15-20 seconds of muscular activity at which

time intramuscular CP is depleted (this provides the physiological basis

for creatine loading which will be discussed in depth in the supplement

section). The CP system operates in the absence of oxygen (it is

anaerobic) and can provide energy very quickly during exercise. However,

as with ATP, it's overall capacity to produce energy is low due to the

limited amounts available. Collectively, stored ATP and CP are known as

the ATP-CP or Phosphagen system. However, the total energy yield from

the ATP-CP system is low due to the small amount of ATP and CP available

in the muscle.

As exercise duration exceeds 10-15 seconds, the ability of the

phosphagen system to provide energy decreases and the body must rely on

other fuel sources to generate ATP. One of these is the breakdown of

glucose or glycogen (known as glycolysis or glycogenolysis respectively

although the term glycolysis will be used here generally to refer to the

breakdown of bodily carbohydrate stores). Glycogen is a storage form of

glucose which is present in muscle and the liver. Glucose circulates in

the bloodstream freely and can be taken up into muscles as needed.

Glycolysis

In a normal individual following a mixed diet, total muscle

glycogen stores may comprise 250-350 total grams of carbohydrate with an

additional 15 grams of carbohydrate circulating in the blood. There is

an additional 90-110 grams of glycogen in the liver but it will be

discussed separately below.

During prolonged exercise at 75% of VO2 max to exhaustion (30-60

minutes or so), muscle glycogen stores will be totally depleted. With

depletion of carbohydrate stores (generally accomplished with either

exhaustive exercise or a carbohydrate free diet or some combination of

the two) followed by several days of a high carbohydrate diet, muscle

glycogen stores can be doubled to 700 grams of glycogen or more.

During exercise, glycogen or glucose is broken down to provide ATP in the

following reaction:

glycolytic enzymes

(Aerobic)

Glucose/Glycogen ---------------------------> ATP + Pyruvate -------->

Krebs cycle, liver, etc

(Anaerobic) |

/

Lactate

The breakdown of glucose or glycogen always initially results in

the formation of ATP and pyruvate. But depending on the availability of

oxygen (which is a function of exercise intensity), the pyruvate

generated has one of two major metabolic fates.

If there is not adequate oxygen present (as with high intensity

exercise), glycolysis only provides 2-3 ATP molecules and the resulting

pyruvate is converted to lactate. Lactate is an acid, causing the

burning sensation felt in the muscles during exercise by lowering pH

inside the muscle. This lowering of muscle pH inhibits glycolysis and

may be one cause of fatigue during high intensity exercise.

In the past, lactate was thought of as only a waste product of

glycolysis that caused fatigue. However, it is now recognized that

lactate is another useful fuel substrate both during and after exercise.

Lactate can be used for energy by slow twitch muscle fibers (Type I) as

well as by the heart. Alternately, lactate can diffuse into the

bloodstream, travel to the liver, and be converted to glucose or glycogen

through the process of gluconeogenesis (literally "the making of new

glucose").

Additionally, following exercise, lactate can be regenerated to

muscle glycogen which may have implications for individuals following a

strict ketogenic diet as glycogen availability is the limiting factor in

many types of exercise. Post-workout glycogen resynthesis from lactate

will be discussed in a later section. This pathway of glycogen and

glucose breakdown is known as fast or anaerobic glycolysis.

If there is adequate oxygen present, glyocolysis produces 38-39

molecules of ATP and the resulting pyruvate is oxidized in the

mitochondria to produce more energy through what is known as the Krebs

Cycle. Alternately, the pyruvate may be released into the bloodstream

where it travels to the liver and is converted to glucose (to be released

back into the bloodstream) through the process of gluconeogensis. This

pathway of glucose or glycogen degradation is known as slow or aerobic

glycolysis.

Liver glycogen

In addition to muscle glycogen and freely circulating blood

glucose, liver glycogen can also play a role in energy production during

exercise. The liver stores up 110 grams of glycogen under normal

conditions and, as with muscle glycogen, this can be increased with

carbohydrate loading. In general, the liver is a storage depot of sorts

for the body. Normally, the liver has a slow output of glucose (from

breakdown of liver glycogen) into the bloodstream. In response to the

release of adrenaline and noradrenaline during exercise (see section on

hormonal reponse to exercise), liver glycogen breakdown and release into

the bloodstream is greatly increased to maintain blood sugar levels.

Additionally, glucagon and cortisol levels (which are also

affected by exercise) further influence liver glycogen release into the

bloodstream. Total depletion of liver glycogen will occur with 24 hours

of total fasting but this may only take several hours during prolonged

exercise (or much less for high intensity exercise). When, liver

glycogen is depleted, blood glucose will also drop and the resulting

hypoglycemia may be one cause of fatigue. Additionally, as it pertains

to ketogenic dieters, the depletion of liver glycogen (and subsequent

drop in blood glucose) below a certain level is necessary for the

intiation of ketogenesis.

It should be noted that total bodily glycogen and glucose stores

can only provide approximately 1500 calories of useful energy (this can

be doubled with carbohydrate loading) or enough to run approximately 15

miles. As this is still fairly limited energy wise, the body has several

other sources of fuel that it can utilize during exercise.

Metabolism of free fatty acids (FFA) and intramuscular triglyceride (TG)

The body has two major stores of fats which can be used during

exercise to provide energy. An 70 kg male with 12% bodyfat has

approximately 70,000 calories of useable energy stored in bodyfat and an

additional 1500 calories stored as intramuscular triglyceride. Assuming

you could use 100% fat for fuel, this would be sufficient to run 720

miles. Even the leanest athlete with only 3 lbs. of bodyfat (containing

approximately 1000 calories worth of useable energy) could run 100 miles

if they were able to use fat for fuel. The question of why humans are

unable to utilize 100% fat for fuel during activity is one that many

researchers have asked themselves and is a topic that will be discussed

in more detail later.

Adipose tissue triglyceride metabolism

As stated, bodily stores of adipose tissue contain approximately

70,000 calories of useable energy stored in the form of triglyceride (TG)

which is the combination of three free fatty acids (FFA) and a glycerol

molecule. But, in order for these triglycerides to be used by the muscle

for fuel, they must go through the following steps:

1. Mobilization: in response to specific hormonal signals during

exercise, adipose tissue TG is broken down within the cell to free fatty

acids (FFA's) and glycerol (which is then released into the bloodstream)

via the enzyme Hormone Sensitive Lipase (HSL). HSL activity is the

ultimate determinant of lipid mobilization during exercise. Adrenaline

and noradrenaline (which increase during exercise) stimulates HSL to

release FFA into the bloodstream while insulin (which decreases during

exercise and increases in response to increases in blood glucose)

inhibits HSL activity and release of FFA to be used for energy. Insulin

and the catecholamines (adrenaline and noradrenaline) are the only two

factors which regulate FFA release from the fat cell (refs).

2. Tranport: FFA's enter the bloodstream where they bind to a fatty acid

binding protein (FABP) to travel through the bloodstream where they are

picked up by the muscle.

3. Uptake: The FFA-FABP complex binds at the muscle and is carried into

the mitochondria for oxidation via the enzyme carntine palmityl

transferase (CPT). *Additionally, once ketogenesis is established in the

liver, circulating free fatty acids will be taken up into the liver and

converted to ketones. The issue of post-exercise ketosis will be

discussed in a later section.*

4. Beta-oxidation: in the mitochondria, the FFA is oxidized yielding ATP

and acetyl-Coa. This acetyl-CoA enters the Krebs cycle to produce more

usable energy.

As will be discussed in a later section, each of the above four

steps has been implicated as the rate limiting factor for the utilization

of FFA during exercise. The beta-oxidation of FFA requires oxygen to

occur (it is sometimes referred to as aerobic lipolysis (refs))

On average, one molecule of FFA will yield 129 ATP or more

depending on the length of the FFA that is burned. Thus, compared to

even aerobic glycolysis, fats provide a much greater energy yield.

However, it should be noted that the oxidation of FFA requires more

oxygen than the oxidation of glycogen or glucose. As will be discussed

later, this has implications for ketogenic dieters.

Intramuscular triglyceride (TG) metabolism

As an additional source of energy, there are droplets of

intramuscular triglyceride stored within the muscle proper. Depending on

a host of factors (to be discussed later), this intramuscular TG will be

oxidized in the same manner as blood borne free fatty acids. As they

exist directly within the muscle fiber, they may exist as a more

immediate source of energy during exercise.

In addition to the use of glycogen/glucose and adipose and intramuscular

TG, the body can also use protein and ketones for fuel during activity.

Protein

Under normal circumstances, protein is not used to a great degree

during exercise. Under most circumstances, it may provide 5% or less of

the total energy yield during exercise. However, with glycogen

depletion, protein in the muscle can be used for fuel either by

conversion to glucose in the liver (again, via gluconeogenesis) or by

direct utilization by the working muscle.

Ketones

The oxidation of ketones for fuel is similar to that of free

fatty acids and intramuscular triglyceride. Under certain conditions,

ketones can enter the muscle where they are converted to acetyl-Coa and

enter the Krebs cycle to produce energy. However, even under conditions

of heavy ketosis, ketones rarely provide more than 7-8% of the total

energy yield which is a relatively insignificant amount. A chart

summarizing the amount of energy available from each fuel source appears

below.

Substrate Total bodily stores Useable energy

----------------------------------------------------------------------

Aerobic/Anaerobic

ATP N/A 1.8 kcal

Anaerobic

CP N/A 8.4 kcal

Anaerobic

Glyocgen (muscle) 250 grams 1025 calories

Depends

Glycogen (liver) 110 grams 451 calories

Depends

Blood Glucose 15 grams 62 calories

Depends

Adipose tissue 7,800 grams 71,000 calories Aerobic

Intramuscular TG 161 grams 1,465 calories

Aerobic

Ketones (!) Varies Varies

Aerobic

Protein (#) Varies 24,000

Note: this assumes a 70kg man with 30kg of muscle and 12% bodyfat.

(!) Ketones rarely provide more than 7-8% of total energy yield even in

highly ketotic individuals (#) Protein only provides 5-10% of total

energy yield and is generally not considered as a major source of energy

during exercise.

Summary

The body can produce energy for exercise by the breakdown of many

different substrates. Generally speaking, fuel utilization can be broken

into two general categories:

Anaerobic energy production

direct breakdown of ATP and CP stored within the muscle, which

predominates during the first 15-20 seconds of exercise anaerobic

glycolysis of muscle glycogen or blood glucose which predominates during

the first 30-70 seconds or so of exercise

Aerobic energy production

aerobic glycolysis of glycogen or blood glucose beta oxidation of

free fatty acids and intramuscular triglycerides oxidation of amino

acids: which generally provides very little of the total energy during

exercise oxidation of ketone bodies: which generally provides very little

of the total energy during exercise

The determination of which substrate provides energy during

exercise depends on a host of factors including availability, the

intensity/duration of exercise, the individual's training status and

gender all of which will be discussed in upcoming sections.

References:

1. "Physiology of Sport and Exercise" Jack H. Wilmore and David L.

Costill. Human Kinetics Publishers 1994.

2. "Endurance in Sport" Ed. R.J. Shephard & P.-O. Astrand. Blackwell

Scientific Publishers 1992.

3. "Exercise Physiology: Human Bioenergetics and it's applications"

George A Brooks, Thomas D. Fahey, and Timothy P. White. Mayfield

Publishing Company, 1996.

Lyle McDonald, CSCS

Some chemistry humor: "If you're not part of the solution, you're part

of the precipitate." -- anonymous

:cool: TJ :cool: