Essential Macronutrient- Protein: Building Block of Body

Protein gives our body structure. Proteins are composed of long chains of amino acids and are found in most foods. Animal sources such as meat, poultry, fish, eggs, and dairy products contain all the essential amino acids, while plant sources like legumes, nuts, seeds, and some grains like quinoa may not contain all essential amino acids but can be combined to form a complete protein diet. This macronutrient is of primary importance as it is the main component that gives form to living beings. Protein builds the structure of our bodies that include the bones, muscles, skin, enzymes, hormones, immunoglobulins, transport proteins, storage proteins, neurotransmitters, etc. They also facilitate many chemical reactions in the body. The genes in our cells trigger the manufacturing of proteins that signal the biochemical reactions within and outside the cell. It’s estimated that there are over one hundred thousand different proteins in the human body. While proteins can be used by the body for energy and provide 4 calories of energy per gram, their primary function is not energy provision. The daily protein requirement varies based on factors such as age, sex, physical activity level and overall health.¹

Protein digestion and breakdown begins in the acidic environment of the stomach. Different amino acids and peptides are absorbed in different ways in the intestinal cell and require ATP for active transport, using carrier molecules. Once inside the intestinal cells, amino acids are used as energy or synthesize enzymes and hormones. From intestinal cells amino acids are also transported to the liver for distribution to other cells. While in the liver, 20% is used to synthesize protein, 60% is catabolized, 20% enters the circulation. The majority of the proteins synthesized in the liver remain in the liver and some are released as plasma proteins like albumin, globulin, lipoproteins, glutathione and more.²

The proteins that pass-through liver to enter the bloodstream become part of the plasma pool amino acids where amino acids are constantly being exchanged in and out of body tissues. Amino acids get broken down if there is high energy demand in the body. If the body needs more protein than it is getting from the diet- the muscles and bones in the body breakdown to provide it to maintain the amino acid pool. The plasma amino acid pool has about 100 grams of amino acids. The source of proteins is less important, body recognizes the amino acids irrespective of it being plant of animal sourced.³ 

Protein Metabolism Pathways:

1. Protein Turnover or Protein Synthesis and breakdown
2. Amino Acid Catabolism and deamination
3. Transamination

Proteins in most tissues including bones and skin are always degraded and resynthesized. Muscle proteins are mostly hypertrophied. Protein synthesis depends on diet, exercise, condition of health, stress, endocrine factors, and gene regulation. It is synthesized in the cells by DNA replication, RNA transcription and translation that determines the sequence of amino acids to be linked together to form specific proteins. These proteins then either stay in the cell or are transported to other parts. Along with carbon and hydrogen bond (carbon skeleton), amino acids contain nitrogen in the form of amines (NH₂) in their chemical structure. When amino acids are needed to form other molecules or are needed in gluconeogenesis to provide energy by the liver, the nitrogens are eliminated which is known as deamination. This is the first step of catabolism. NH₂ group breaks away to form ammonia (NH₃) which is toxic. NH₃ enters the urea cycle (Fig-1) in the liver to form the non-toxic urea which is excreted by the kidney. People with kidney diseases may not be able to excrete urea properly where ammonia levels may build up, they need to stay on protein restriction diet to avoid building up urea. The remaining carbon-hydrogen chain or carbon skeleton after the release of the NH₂ is called alpha-ketoacid. Amino acids might simply transfer their NH₂ group to another amino acid carbon skeleton (alpha-ketoacid) to form a new amino acid. This is called transamination.^{4, 17}

Fig-1: Urea production in liver, secreted from liver to be incorporated in kidney for excretion with urine.⁴

Almost all food contains protein. Good quality protein is available in lean meat of beef and wild games, poultry-chicken, turkey, duct, fish, seafood, eggs, cottage cheese, plain yogurt, beans, legumes, tofu etc.¹⁸

Human bodies need 20 amino acids, and the body can synthesize 11 of them. The remaining 9 amino acids are called essential amino acids as they are needed from the diet.⁵

Proteins are always being built and broken down in our cells. This requires energy and protein for raw materials. So, it is essential to have good proteins in our diet to avoid protein deficiency related hormonal imbalances, depressed immune function, and poor recovery from illness.¹⁹

Proteins are usually not reserved as fuels for the body. However, in some situations when carbohydrate intake is low, glycogen storage from muscle and liver are depleted from fasting or high endurance activities, fat energy store is also depleted or not well utilized, amino acids are utilized as energy source. This is usually the case during starvation. The amino acids that can enter gluconeogenesis are called glucogenic amino acids, and there are other amino acids that can form ketone bodies which are called ketogenic amino acids.⁴

Protein Burns Fat:

Protein stimulates glucagon release from pancreas that breaks down liver glycogen to glucose. While glucagon is active, insulin production is low which increases utilization of fat as a fuel source as well.

Protein triggers growth hormone release from the anterior pituitary which in turn releases fatty acids from adipose tissue into the blood.

Food itself takes up a lot of energy to break down in the body. The process of eating, digestion, absorption, and assimilation of food expends a lot of energy which is known as the thermic effect of food. Among all macronutrients, protein has the highest thermic effect, meaning it increases the metabolism of the body.

Protein also stimulates release of cholecystokinin from the stomach that travels in the bloodstream to inform the hypothalamus that the stomach is full, thus suppressing the appetite.⁶

Human Body Energy Need:

Basal Metabolic Rate (BMR): The human body keeps burning calories even while resting or sleeping as the heart needs to pump, respiration needs to continue, brain needs to function, nutrients within cells continue to process, and cells are being multiplied. This is the body’s basal metabolic rate or BMR. It is the minimum level of energy needed to maintain vital functions of the body. There are many methods that can calculate an individual’s BMR. It is estimated that 70% of total energy burned each day is to keep us alive.⁷

To reduce body weight, it is advised to increase BMR which means increasing metabolism and that happens through regular physical exercise and activities.

Resting Metabolic Rate (RER): It is similar to BMR, resting metabolic rate is measured using oxygen consumption and it is considered to be the energy the body is expending in a relaxed state but not in a fully inactive state. There is only a 10% difference between BMR and RMR with RMR being higher.^7,8 

Thermic Effect of Food (TEF): It is the increase in the metabolic rate that occurs after eating food. Thermic effect is the amount of energy that is required to breakdown the food for utilizing the nutrients through the processes of digesting, absorbing, and transporting.⁹ It is 10% of the total energy expended daily.¹⁹

• Fat provides 9 calories of energy per gram. Its TEF is 0-5%
• Carbohydrates provide 4 calories of energy per gram. Its TEF is 5-15%
• Protein provides 4 calories of energy per gram. Its TEF is 20-30%¹⁰

Physical Exercise Effect: This is energy expended on daily exercise like going for a run, high intensity activity, low to moderate activity, yoga, etc. It varies from person to person. It can be 10-15% or even less for sedentary people but can be as high as 30% for highly active individuals.²⁰

Non-exercise Activity Thermogenesis (NEAT): This is the part of daily life movement that is not deliberate exercise. It represents daily activities like moving around in the house, walking, standing, fidgeting, pacing, housework, carrying things, etc.¹¹

The macronutrients are all working simultaneously, it is essential to have a balanced diet for physical and mental wellbeing. The goal of food metabolism is to make the Adenosine Triphosphate (ATP) molecule, the primary molecule of energy in the mitochondria of cells.

The body only stores about 80-100 grams of ATP, just enough for a few seconds of intense action. For a 68 kg weight person, 51 kg of ATP is used in a day, almost 75% of the body weight. The ATP breaks into Adenosine Diphosphate (ADP) and a free phosphate (P), this reaction breaks the adenosine-phosphate bonds which generates the energy for the cellular functions. The ADP and P are again reprocessed to make ATP and the cycle continues. For replenishing the body with continuous supply of ATP, it depends on how quickly energy is needed, the speed of reactions, the available nutrients (carbohydrates, fats, proteins) and whether there is enough oxygen.²¹ Mitochondria in the cell is responsible for ATP formation. Higher quality and high number of mitochondria always produce more energy. Athletes and people habituated with regular exercise usually have better quality and high density of mitochondria in muscle cells which generates more ATP and ultimately increased metabolism.

The Energy Systems at work during a sprint, followed by a slower jog, then an eventual walk/ Workout Followed by Slowing Down:

1. ATP-PCr System:

When the body suddenly bursts into a sprint, sudden heavy lifting, or throwing a high-speed ball, the first 2 seconds use up the stored ATP. After that the ATP-PCr system in the cytosol of cell kicks in which provides energy for 10-15 seconds. The Phosphocreatine (PCr) molecule in the cytosol is broken down by creatine kinase enzyme into creatine and phosphate which also generate energy. This phosphate along with the energy generated uses ADP in the cytosol to create ATP which can provide energy for about 10-15 seconds in a high-power short duration workout.^12,22

2. Glycolytic Pathway: moderate power moderate duration

The glycolytic system is triggered at the same time as the ATP-PCr but it takes over 15 seconds into the sprint where energy was being provided by the ATP-PCr system. The stored glycogen in the muscle, available blood glucose and the glycerol part of the triglycerides help generate ATP in glycolysis. In this energy system, one molecule of glucose yields a net of two molecules of ATP, pyruvates and NAD+. Continuation of intense workout will release H+ from glycolysis as well which then combines with pyruvate to form lactic acid and with NAD+ to form NADH that prevent muscle fatigue. These two helps continue running but only for two minutes, and eventually the excessive H+ ion formation will make muscles acidic and force the body to slow down. When the body finally slows down then it enters a slow glycolytic phase where the pyruvates will not turn to lactic acid but instead will convert to Acetyl CoA and enter the Krebs cycle. Examples: moderate runs of 200-400 yards.^12,23  

3. Krebs Cycle and Oxidative Phosphorylation:

Acetyl CoA formation is the entry point of Krebs cycle. Krebs cycle and oxidative phosphorylation provides ATP slowly but can keep the body going indefinitely in low intensity activity.²⁴

Krebs cycle and electron transport mechanism both occur in the mitochondria. The Acetyl CoA molecules made from degradation and metabolism of carbohydrate, fats, and protein from different pathways, is the entry point of the Krebs Cycle. Then oxidative phosphorylation process happens in the inner matrix of the mitochondria. Oxidative phosphorylation is composed of the electron transport chain and chemiosmosis. In the electron transport chain, electrons are passed from one molecule to the other and energy gets released while this happens which is used to form the ATP by the chemiosmosis process. Oxygen sits at the end of the electron transport chain which accepts the electrons and adds hydrogen molecules to form water. If there is no oxygen (if the person is not breathing enough oxygen) to accept the electrons, then the electron transport chain will not function, and no ATP will be formed from chemiosmosis.¹³

Example of Activity- 3-mile run, marathons, low level manual labor.

Fig-2: Mitochondrial outer and inner membrane, oxidative phosphorylation.¹³

The above-mentioned systems explain the systems involved in ATP production. During exercise of any kind, skeletal muscle contraction requires constant supply of ATPs. At resting stage, a single muscle cell contains 1 billion ATP molecules which are used and replenished every two minutes. While exercising, production can increase by 1000-fold. The sources of yielding this high concentration of ATPs are- the fatty acids in the bloodstream, the stored triglycerides in the muscle cells, glucose from the blood stream, and the glycogens stored in the muscle.¹⁴

During Sleep:

Sleep is characterized by absence of muscle tone, decreased body temperature, and an absence of food and water intake. However, the brain needs a continuous supply of energy, and this energy need is state dependent; meaning it changes with sleep, rest, and wakefulness. Studies recommend muscle glycogen is not a major fuel substrate during deep sleep. During sleep, fatty acid oxidation and ketone bodies provides energy to the brain. Midway through the sleeping period, when the body is in deep sleep, fatty acid oxidation peaks and decreases to almost zero at the end of an eight-hour sleeping period.

Both oxygen availability and consumption of oxygen of brain is high during deep sleep. More calories are burned at this stage as well for overall body restoration. Fatty acid provides more energy than glucose and is able to utilize the high oxygen available during sleep. Fatty acid oxidation also produces double the amount of water than that is produced from glucose breakdown which protects the brain from excessive water loss and electrolytes during sleep. These are possibly the reasons why fatty acid oxidation is the major source of energy during deep sleep.¹⁵

It should be noted that all kinds of movement lead to energy burn. Exercise of any kind enhances physical and mental wellbeing. Regular exercises like weight training, endurance exercise, high intensity interval training increases the muscle mass which will require more calorie burning and raise basic metabolic rate. This will keep an individual in a sustained high energy burning state even on the days they are not exercising. It is recommended to do at least 30 minutes of cardio (walking, running, swimming, cycling, cross-training) three times a week along with weightlifting and resistance training as the most basic form of exercise to enhance metabolism.¹⁶

Author of this article

Dr. Maliha Mannan Ahmed, MBBS (BMC), MBA (ULAB), Masters in Healthcare Leadership (Brown University, USA) and Level 1 Certification on Precision Nutrition. 

The Executive Editor of The Coronal.

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