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Proteins are responsible for nearly all bodily and cellular functions: from structural proteins in bones; contractile proteins in muscles; transport proteins in blood plasma; to hormones, antibodies, cell receptors, ion channels, and enzymes that catalyze almost every chemical reactions in biological systems. Proteins are polymers of amino-acids linked together by peptide bonds. An amino-acid consists of an amino group, a carboxyl group, and a unique side chain, connected to a central carbon, the α-carbon. Instead of being an extended chain of amino-acids, a protein usually folds into a three-dimensional conformation that is critical for its functions. The structure forms as a result of interactions between the side chains of amino-acids, and is thus dictated by the amino-acid sequence. Of the 20 amino-acids that make up proteins, nearly half are essential, meaning the body cannot synthesize them and must get them from the diet. Animal proteins are usually considered high-quality, complete proteins, because they have similar amino-acid composition as human proteins, and can thus provide all the required amino-acids, but a combination of a variety of plant foods may also do the job. Proteins in foods are digested in the stomach and small intestine, by the action of stomach acid, which denatures proteins, and several enzymes that hydrolyze peptide bonds. Together they break down proteins into individual amino acids, which are then absorbed into the bloodstream and transported to the liver. The liver uses these amino-acids to synthesize new proteins, most of which are plasma proteins. The liver also distributes free amino-acids to other tissues, for synthesis of tissue-specific proteins. Proteins are synthesized based on genetic information of the cell, using the genetic code, and regulatory signals. Each cell has a characteristic collection of proteins, specific to its functions. Body proteins are constantly renewed. Older proteins are broken down into free amino-acids, which are recycled, they combine with dietary amino-acids to make new proteins. Unlike carbohydrates and lipids, proteins cannot be stored for later use. Once the cellular requirement for proteins is met, excess amino-acids are degraded and used for energy, or converted into glucose or fatty acids. Use of amino-acids for energy production also occurs when there is energy shortage, such as during prolonged exercise or extended fasting. Since there are no nitrogenous compounds in the energy production pathways, the first step in amino-acid degradation is the removal of the amino group, by deamination or transamination, to produce keto-acids. Some amino-acids can be directly deaminated, while others must transfer their amino group to α-ketoglutarate to form glutamate, which is then deaminated to recycle α-ketoglutarate. Depending on their side chains, keto-acids from different amino-acids may enter the metabolic cycles at different points. They may be converted to pyruvate, acetyl-CoA, or one of the intermediates of the citric acid cycle. Some of these reactions are reversible. When amino-acids are in short supply, citric acid intermediates can be aminated to create new amino-acids for protein synthesis. Deamination produces ammonia, which is toxic if accumulated. The liver converts ammonia to urea to be excreted in urine. Extreme diets that are excessively high in proteins may overwhelm the kidneys with nitrogenous waste and cause renal damage.

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Although the term “lipid” includes several types of molecules, lipid metabolism usually refers to the breakdown and synthesis of fats. Fats are triglycerides, they are esters of glycerol and three fatty acids. Fats can come from the diet, from stores in adipose tissue, or can be synthesized from excess dietary carbohydrates in the liver.
Dietary fats are digested mainly in the small intestine, by the action of bile salts and pancreatic lipase. Bile salts emulsify fats. They act as a detergent, breaking large globules of fat into smaller micelles, making them more accessible to lipase. Pancreatic lipase then converts triglycerides into monoglycerides, free fatty acids, and glycerol. These products move into the cells of intestinal epithelium – the enterocytes, inside which they re-combine again to form triglycerides. Triglycerides are packaged along with cholesterol into large lipoprotein particles called chylomicrons. Lipoproteins enable transport of water-insoluble fats within aqueous environments. Chylomicrons leave the enterocytes, enter lymphatic capillaries, and eventually pass into the bloodstream, delivering fats to tissues. The walls of blood capillaries have a surface enzyme called lipoprotein lipase. This enzyme hydrolyzes triglycerides into fatty acids and glycerol, enabling them to pass through the capillary wall into tissues, where they are oxidized for energy, or re-esterized for storage.
Fats that are synthesized endogenously in the liver are packed into another type of lipoprotein, the VLDL, to be transported to tissues, where triglycerides are extracted in the same way.
When required, fat stores in adipose tissue are mobilized for energy production, by the action of hormone-sensitive lipase, which responds to hormones such as epinephrine.
Lipid metabolism pathways are closely connected to those of carbohydrate metabolism. Glycerol is converted to a glycolysis intermediate, while fatty acids undergo beta-oxidation to generate acetyl-CoA. Each round of beta-oxidation removes 2 carbons from the fatty acid chain, releasing one acetyl-CoA, which can then be oxidized in the citric acid cycle. Beta-oxidation also produces several high-energy molecules which are fed directly to the electron transport system. Fats yield more energy per unit mass than carbohydrates.
When acetyl-CoA is produced in excess, it is diverted to create ketone bodies. During glucose starvation, ketone bodies are an important source of fuel, especially for the brain. However, ketone bodies are acidic, and when produced in excess, can overwhelm the buffering capacity of blood plasma, resulting in metabolic acidosis, which can lead to coma and death. Ketoacidosis is a serious complication of diabetes, in which cells must oxidize fats for fuel as they cannot utilize glucose. Extreme diets that are excessively low in carbohydrates and high in fat may also result in ketoacidosis.
On the other hand, diets that are high in carbohydrates generate excess acetyl-CoA that can be converted into fatty acids. Synthesis of fatty acids from acetyl-CoA is stimulated by citrate, a marker of energy abundance, and inhibited by excess of fatty acids. Fatty acids can be converted into triglycerides, for storage or synthesis of other lipids, by combining with glycerol derived from a glycolysis intermediate.

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Carbohydrates are biomolecules that consist of carbon, hydrogen and oxygen atoms, usually in the ratio of 1:2:1. Carbohydrates play crucial roles in living organisms. Among other functions, they serve as major sources of energy, and structural components.
Carbohydrates are made of base units called monosaccharides. Monosaccharides consist of a carbon chain with a hydroxyl group attached to all carbons except one, which is double-bonded to an oxygen. This carbonyl group can be in any position along the chain, forming either a ketone or an aldehyde. Some monosaccharides share the same molecular formula, but are different in structure due to different positions of atoms. These seemingly small structural details result in completely different sugars, with different properties and metabolism pathways.
Monosaccharides exist in open-chain form and closed-ring form. The ring forms can connect to each other to create dimers, oligomers and polymers, producing disaccharides, oligosaccharides and polysaccharides, respectively. Examples of disaccharides are sucrose, maltose, and lactose. Common polysaccharides include glycogen, starch and cellulose, all of which are polymers of glucose. Their differences arise from the bonds between monomers. Glycogen and starch serve as energy storage in animals and plants, respectively. Their monomers are bonded by alpha-linkages. Some monomers can make more than one connection, producing branches. Starch in food can be digested by breaking these bonds, with the enzyme amylase.
Cellulose, the major structural component of plants, consists of unbranched chains of glucose bonded by beta-linkages, for which humans lack the enzyme to digest. Cellulose and other non-digestible carbohydrates in food do not supply energy, but are an important part of human diet, known as dietary fibers. Fibers help slow digestion, add bulk to stool to prevent constipation, reduce food intake, and may help lower risk of heart diseases.
During digestion, digestible carbohydrates are broken down into simple sugars. Digestion of starch starts with amylase in the saliva and continues in the small intestine by other enzymes. Sucrose and lactose are hydrolyzed by their respective intestinal enzymes. Simple sugars are then absorbed through the intestinal wall and transported in the bloodstream to tissues, for consumption or storage.
Foods rich in simple sugars deliver glucose to the blood quickly, and can be helpful in case of hypoglycemia, but regular diets of simple sugars produce high spikes of glucose and may promote insulin insensitivity and diabetes. Complex carbohydrates take longer to digest and release simple sugars. Eating complex carbohydrates helps dampen the spikes of blood glucose and reduce diabetes risk.
Glucose is central to cellular energy production. Cells break down glucose when energy reserves are low. Glucose that is not immediately used is stored as glycogen in liver and muscles. Glycogen is converted back to glucose when glucose is in short supply.
Energy production from glucose starts with glycolysis, which breaks glucose into 2 molecules of pyruvate, releasing a small amount of energy. Glycolysis involves multiple reactions and is tightly regulated by feedback mechanism.
In the absence of oxygen, such as in the muscles during exercise, pyruvate is converted into lactate. This anaerobic pathway produces no additional energy, but it regenerates NAD+, which is required for glycolysis to continue.
When oxygen is present, pyruvate is further degraded to form acetyl-CoA. Significant amounts of energy can be extracted from oxidation of acetyl-CoA to carbon dioxide, by the citric acid cycle and the following electron transport system. When present in excess, acetyl-CoA is converted into fatty acids. Reversely, fatty acids can breakdown to generate acetyl-CoA during glucose starvation.
When blood sugar level is low and glycogen is depleted, new glucose can be synthesized from lactate, pyruvate, and some amino-acids, in a process called gluconeogenesis, which is almost the reverse of glycolysis.
Metabolism of other simple sugars converges with the glycolytic pathway at different points. For example, fructose feeds into the pathway at the level of 3-carbon intermediate, and thus bypasses several regulatory steps. Fructose entrance to glycolysis is therefore unregulated, unlike glucose. This means production of acetyl‐CoA from fructose, and its subsequent conversion to fats, can occur unchecked, without regulation by insulin.