Breakdown and utilization of proteins and fats is essential for their targeted functions in the body. The human body derives energy from fuel nutrient molecules like carbohydrates, fats, and proteins. Proteins and fats are different classes of macronutrients with complex structures and varied functions. Proteins are present in every part of the cell and are the building blocks of life. They are present in hormones, enzymes, hair, nails, and skin.
Proteins like enzymes and hormones are made inside the human body with the help of raw materials obtained from protein-rich food. Meat, poultry, eggs, legumes, nuts, seeds, milk, and other dairy products contain protein.
Fat or, in general lipids, functions metabolically and structurally. Our body does not synthesize essential fatty acids viz. omega-3 fatty acids and omega-6 fatty acids are obtained through food. Structure, functions, and how these macromolecules are being digested are explained in this article.
Protein Structure
Proteins are the polymer of amino acids. An amino acid comprises a central carbon atom with an amino group (–NH2), carboxylic group (–COOH), hydrogen, and a unique organic R group attached to it. Twenty different amino acids exist in nature by just changing the R group.
The simplest amino acid is glycine with hydrogen as the R group. Amino acids form chains by a covalent peptide bond. When two amino acids are joined through a peptide bond, the structure is known as a dipeptide.
The smallest protein in a human body is the Thyroid Releasing Hormone (TRH) with 234 amino acids.
There are four levels of protein structure- primary, secondary, tertiary, and quaternary structures. The primary structure is just a simple polypeptide chain. When the principal structure or polypeptide chain folds to give a repetitive structural pattern, it is called the secondary structure of a protein.
The three-dimensional fold of a polypeptide chain gives the tertiary structure. Quaternary structure is formed when two or more polypeptides are folded to become different protein subunits but function as one protein complex.
Hence, it is the sequence of amino acids that decides the three-dimensional structure of a protein. A single change in amino acid could alter the whole property and structure of proteins, and thus different combinations of amino acids make different types of proteins.
Protein Digestion
Protein digestion starts in the stomach. Enzyme pepsin, along with gastric juice produced in the stomach, degrades the proteins in the food. Hydrochloric acid produced by the gastric gland of the stomach is required to activate the inactive form of Pepsin, Pepsinogen, to an active enzyme, Pepsin.
Pepsin breaks proteins into smaller polypeptides and their corresponding amino acids. The food churned in the stomach, along with gastric enzymes and juices, enters the small intestine.
The small intestine releases digestive enzymes, proteases trypsin, chymotrypsin, and carboxypeptidase, helping in protein digestion. These enzymes convert complex proteins into smaller amino acids.
Amino acids are thereby transported across the intestinal mucosa, where they are used to create new proteins or else converted into fats or acetyl CoA and used in the TCA cycle. Essential amino acids cannot be synthesized in our body, and hence we get it through diet. So these are useful for the synthesis of proteins.
When the enzymes, hormones, and other cellular signaling peptides are no longer needed, they are degraded to make new proteins. This further degradation occurs through lysosomal degradation and also by the process of ubiquitination.
Proteins for degradation enter lysosome via fusing with the membrane, an event known as autophagy.
Cytoplasmic Components
Cytoplasmic components such as defective or extra organelles, unused proteins, or protein aggregates are degraded using lysosome. The mode of degradation is analogous to phagocytosis. Here, an autophagosome fused with lysosome engulfs the proteins that are digested by the Lysosomal proteases. The structure matures and degrades the proteins internally. Lysosomal permeases transport amino acids to the cytoplasm, where it is often reused for other purposes.
In the process of ubiquitination, two protein complexes are required- Ubiquitin and Proteasome. Protein degradation happens inside the inner chamber of proteasome through a nucleophilic and enzymatic attack.
The proteasome can degrade individual cellular proteins in a highly selected manner. Proteins to be degraded are covalently attached to ubiquitin molecule and associate with proteasome inside the lysosome. This is an ATP dependent process. The proteasome structure is such that the ubiquitin molecules inside it can use the products of ATP hydrolysis to unfold the protein structure to simpler amino acids.
Amino acids can be further condensed to carbon and nitrogen skeletons. The carbon part can be transformed into TCA intermediates. Nitrogen is converted into ammonia and then urea through the urea cycle and can be flushed out of the human body. Nitrogen can also serve as the precursors of the amino acid or nucleic acid biosynthesis.
Functions of Proteins
Proteins have very diverse functions in our bodies, and their occurrence is beyond imagination.
Protein such as Antibodies can Bind to Different Molecules
An antibody is produced as a result of the response to an antigen that has entered the body. Antibodies are specific to their antigens. Antibodies can alter their forms to best suit the antigen and destroy it. They have two identical binding sites and can bind two similar antigens at a time. IgM is a type of antibody that contains ten identical binding sites.
Other than antibodies, cell surface receptors, or specific ligands are also made of proteins that can bind to their affinity molecules.
Carrier Proteins and Channel Proteins
Cell membranes possess different receptors for various reasons. One reason is that when the protein binds to the cell membrane receptor, the membrane channel opens up from one side for some molecules to pass along the concentration gradient. This function is done by channel proteins, as suggested by the name. For example, the Sodium-Potassium channel can open up for specific ions.
Carrier proteins bind to molecules who wish to cross the membrane. Some molecules are hydrophobic or impermeable and cannot cross the membrane. For example, NADH is impermeable to the inner membrane of the mitochondria; as a result, there is a need for a Malate-aspartate shuttle system. When malate enters the membrane, it is reduced to form NADH inside the mitochondria with the byproduct of oxaloacetate.
Structural Function
Globular and fibrous proteins are some of the structural proteins. Globular proteins can act as enzymes, transporters, and hormones and have some regulatory roles. They include hemoglobin, myoglobin, and albumins.
Fibrous proteins include keratin, collagen, actin, tubulin, elastin, etc. They are found in the hair, nail, silk of spider, beaks, scales, feathers, etc. Collagen is the most abundant fibrous protein found in mammals, which are present in the cornea, cartilage, bone, blood vessels, and gut.
Hormones and Enzymes
Enzymes and hormones are proteins that serve as biological catalysts and can coordinate different activities of our body, respectively.
Protein as a Drug Target
Identification of an accurate drug target is very critical in any drug development program. Target proteins are the ones in which a particular drug can bind. Therefore, the protein target should possess a high affinity specific binding site and should be able to fold or alter the structures of bound molecules resulting in the altered function of the protein. Because there are over-expressed proteins in many cancers, and targeting them will increase selectivity as they interfere in the cancer progression.
Structure of Fats
Fats are classified as lipids and are made of glycerol and fatty acids. Glycerol is a three-carbon molecule with three hydroxyl groups. It is through this hydroxyl group, and fatty acid is being attached to form glycerides. Fatty acids are long-chain hydrocarbons with a functional group of carboxylic acid at one of its end. Glycerides can be named based on the number of fatty acids attached. If fatty acids occupy one, two, and three hydroxyl groups, they are called as mono-, di- and triglycerides, respectively.
Phospholipids
They have either glycerol or sphingosine as the backbone where fatty acids and phosphate are attached to it. Thus the structure is amphipathic with both hydrophilic and hydrophobic nature. They form the bilayer where polar phosphate interacts with the water molecules, and the non-polar fatty acid chain is immersed in the membrane.
Glycolipids
These are also a type of phospholipids with a sphingosine backbone where the phosphate replaced with galactose or glucose (a sugar).
Another type of lipid, cholesterol, is a fused structure containing three rings with six carbon atoms with a hydroxyl group and one ring with five carbon attached with a saturated hydrocarbon chain. This is the primary structure for the sex hormones, testosterone, and oestradiol. Also, the structure of vitamin D is derived from cholesterol.
Breakdown of Fats
While protein digestion starts in the stomach by the enzyme pepsin, lipid breakdown begins in the small intestine. Lipases are the enzymes that help in the breakdown of lipid complexes.
Ester bond present in the lipid is the target of lipase, and the enzyme hydrolyses these bonds into simpler forms. Human gastric lipase and human pancreatic lipase are the two main enzyme systems for the efficient lipid digestion.
Other lipases include pancreatic carboxylesterase, pancreatic phospholipase A2, and pancreatic lipase related protein-2. Bile juice from the liver also contributes to the digestion.
Fatty acids obtained from the diet are saturated in the case of animal fats and polyunsaturated in the case of plants. Triglycerides cannot be absorbed in the intestine, and hence there is a need for the enzymes mentioned above to help indigestion. Triglycerides are broken down into monoglycerides and diglycerides along with some free fatty acids.
As these molecules are hydrophobic, micelles transport free fatty acids and monoglycerides into the enterocytes for absorption. Phospholipids such as phosphatidylcholine are the second crucial dietary lipid after triglycerides. The enzyme A2 cleaves phospholipids present in the lumen of the gut. They are digested to free fatty acids and also phosphocholine.
Once they are transported into the cell, they are packaged into phospholipid vesicles called chylomicrons. These aid fats and cholesterol to move in the hydrophilic environment of lymphatic or circulatory systems. The lymphatic system and villi of the intestine are connected through lacteals. Via lacteals, chylomicrons enter the lymphatic system. They are then transported to the circulatory system, where they can be stored in fat cells called adipocytes. Adipocytes make up the adipose tissue found throughout the body.
Energy Production from Fat
Triglycerides are first broken to glycerol and fatty acids in order to obtain energy. The process is called lipolysis, which is mentioned earlier. Now the resulting saturated or unsaturated fatty acids are digested further by the process called beta-oxidation of fatty acids or fatty acid oxidation, which begins within the cytoplasm. Fatty acids are converted into fatty acyl CoA, which is unable to cross the mitochondrial membrane.
Membrane Crossing
Membrane crossing is done with the assistance of the carnitine molecule by combining with the fatty acyl CoA. The combination can now pass the membrane, and once inside the membrane, the fat acylcarnitine molecule is converted back to fatty acyl CoA and then to acetyl CoA. The acetyl CoA can enter the TCA cycle to produce ATP. For instance, if palmitoyl CoA (16 carbon long fatty acid) is oxidized, a net total of 106 ATPs are produced.
If the quantity of acetyl CoA produced is high, it is converted into ketone bodies. These are useful when the glucose level goes down in the body. They serve as the energy source. This process of reverting of acetyl CoA to ketone bodies is termed ketogenesis that occurs in the mitochondria of liver cells.
Lipogenesis
Lipids can be made from acetyl CoA when the body derives energy from the carbs. When we consume an excess of carbs, acetyl CoA produced is additionally high. Therefore, there is no need for energy derivation from fats, and acetyl CoA is reverted to cholesterol, steroids, and triacylglycerides. The process is lipogenesis and occurs in the cytoplasm of adipocytes and liver cells.
Roles of Lipids
As mentioned in previous sections, there are different types of fats with varied roles.
Dietary Fats
Dietary fats include saturated, trans, monounsaturated, and polyunsaturated fats. They differ in their chemical structures and properties. The saturated and trans fats are bad for the body as they increase bad cholesterol or low-density lipoproteins (LDL). Monounsaturated and polyunsaturated fats, on the contrary, are perfect for the body and are consumed as a part of a healthy diet. They help in reducing LDL levels.
Monounsaturated and polyunsaturated fats are found in poultry, fish, legumes, low-fat dairy products, and nuts. Bad fats are mostly part of fried and processed foods like chips, deep-fried fast foods, biscuits, pastries, and pizzas, to name a few.
Structural Components of Cell
The cell membrane is made of a phospholipid bilayer. They serve as the protective barrier for cell and organelle membranes. Cholesterol manages fluidity of membranes by stacking in the bilayer.
Storing Energy
The food we eat consists of fat that are digested into its simpler forms. During the catabolism of lipids, intermediates of the TCA cycle are formed, which can be used to produce energy. Fat cells are specialized for fat storage present beneath the epidermal layer.
Insulation and Protection
Vital organs are covered inside the fat. The layer of fat insulates the body from extreme temperature and keeps a constant internal temperature, thus giving protection.
Chemical Messengers
Lipids also play a role as signaling molecules. Since they are hydrophobic in nature, they make the best molecules for signaling. In their esterified form, they carry messages to different cells.
Role in Inflammation
The essential fatty acids, such as linolenic acids, are predecessors of prostaglandins, thromboxanes, prostacyclins, leukotrienes, and resolvins, etc. that play a crucial role in pain, fever, inflammation and blood coagulation.
Fat-soluble Vitamins
Vitamin A, D, E, and K are fat-soluble vitamins with essential functions:
Vitamin A is vital for healthy skin, bone, and teeth. Vitamin D derived from cholesterol is a non-essential vitamin made in the body. These vitamins aid in the absorption of calcium and phosphate in the intestine. Vitamin E is known to scavenge free radicals and also affect enzyme activity. Vitamin K is integral for blood clotting, bone metabolism and is also a cofactor for certain enzymes.
Health Risks
Hyperlipidemia and Development of Atherosclerosis and Coronary Heart Diseases
This is the condition where there is a high level of cholesterol and triglycerides in the blood. It can lead to fatty deposits and show the risk of blockage in arteries. Trans fat increases the LDL and transports, stores cholesterol within the bloodstream, and lowers the HDL. This forms plaque in arteries and blocks the coronary artery leading to heart attack, stroke, and atherosclerosis.
Cancer Development
Cancer cells require a vast amount of energy for accelerated proliferation. Mutation in genes required for lipid metabolism results in an altered or overexpression or underexpression of genes that eventually leads to cancer. For instance, the accumulation of cholesterol ester leads to breast cancer.
Mutation in any genes results in the addition or deletion of amino acid and, in turn, alters the reading frame for protein synthesis. This mutated protein could be folded to any enzymes- of lipid metabolism, protein degradation, glucose biosynthesis, etc. Any alteration in protein can lead to cancer and other genetic disorders.
Risk of Alzheimer Disease
Apolipoprotein impairs lipid transport, glucose metabolism, and cerebrovascular function that can cause early onset of Alzheimer’s disease at a lower age.
Obesity
When lipids are not used correctly in the body, and the rate of storage is high, it leads to the condition of obesity.
Protein Deficiency Disorders
Kwashiorkor and marasmus are two primary syndromes associated with protein deficiency that causes swelling, fatigue, and even death.
Health consequence of High Protein Intake
High protein intake could lead to kidney stones, liver malfunction, and osteoporosis. Red meat is a rich source of protein, and the high consumption of such food gives a chance of colon cancer.
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Main Image- Karolina Grabowska@Pexels
Kerala, India
M.Sc Microbiology
