Metabolism

Metabolism

Food products that are absorbed through the GI tract are in the form of monosaccharides (from carbohy-drate); fatty acids, glycerol, and monoglycerides (from fat); and amino acids (from protein). Most of these molecules are used for supplying the energy re-quired for normal functioning, such as muscle con-traction, active substance transport, protein synthe-sis, and cell division. Some are used to synthesize complex molecules, such as enzymes and muscle pro-teins, and cell repair. Others are changed to storage forms for future use. All of these changes are initiated by metabolism.

Metabolism refers to all of the chemical reactionsthat take place in the body. Certain reactions result in synthesis, or formation and are known as an-abolism. Other reactions result in product break-down (catabolism). For example, amino acids may be linked to form proteins or fatty acids used to form phospholipids or glucose molecules linked to form glycogen. This is anabolism. Glycogen may be broken to release glucose. This is catabolism. In both an-abolism and catabolism, energy is used or released. The molecule that participates in exchange of energy is adenosine triphosphate (ATP).

ATP consists of an adenine and ribose molecule and three phosphate groups. During anabolism, one phosphate group is split, and ATP is converted into ADP, phosphate group, and energy.

ATP → ADP+ P (phosphate group)+energy

Part of this energy is used for the anabolic reac-tion, and the remaining energy is in the form of heat.

During catabolism, part of the energy is trans-ferred to ADP to form ATP during the breakdown of complex molecules. The remaining energy is released as heat, which may be used to maintain body tem-perature.

Energy+ADP+P (phosphate group) → ATP

In this way, ATP provides a linkage between an-abolism and catabolism.

CARBOHYDRATE METABOLISM

The absorbed carbohydrates in the gut are in the form of glucose, galactose, and fructose (monosac-charides). From here, the monosaccharides are trans-ported to the liver by the portal circulation. In the liver, practically all galactose and fructose is con-verted to glucose. Glucose is then transported in the blood to various tissue. In the tissue, glucose may be used for (A) production of ATP; (B) formation of amino acids; (C) conversion into glycogen (glycogen-esis) by the liver and muscle cells; or (D) formation of triglycerides, fat (lipogenesis).

Glucose is transported across the plasma mem-brane of cells by facilitated diffusion . Therefore, special transport proteins must be present in the cell membrane for glucose to be transported into the cytoplasm. The hormone insulin increases the number of transport proteins in the cell mem-brane, facilitating the entry of glucose into cells. In the absence of insulin, the entry of glucose into cells is diminished. That is why the lack of insulin (dia-betes mellitus) results in increased blood glucose lev-els. (Note that hepatocytes and neurons do not de-pend on insulin for glucose entry). Once glucose enters the cytoplasm, it is phosphorylated (combined with phosphate group), which prevents glucose from being removed from the cell.

Inside the cell, glucose is oxidized (process in which electrons are removed) to form ATP. This process, known as cellular respiration, involves many steps. Initially, glucose is oxidized to form two pyruvic acid molecules (glycolysis). During glycoly-sis, two ATP molecules are formed. Because oxygen is not required for this step, it is known as anaerobicrespiration. Depending on the availability of oxygen,pyruvic acid may be converted to lactic acid or may enter the Krebs cycle. In skeletal muscle, for exam-ple, pyruvic acid is converted into lactic acid when oxygen availability is scarce. The lactic acid diffuses out of the cell and, on reaching the liver via blood, is again converted to pyruvic acid.

Glucose → 2 pyruvic acid → 2 lactic acid (anaerobic pathway)

Krebs cycle or the citric acid cycle is a series ofchemical reactions facilitated by different enzymes that occur in the matrix of the mitochondria. During these reactions, ATP is manufactured, with release of carbon dioxide and water.

Glucose → 2 pyruvic acid(aerobic pathway) → Krebs cycle

The pyruvic acid is converted to acetyl-coenzyme A before it enters the Krebs cycle inside the mitochon-drion. Pyruvic acid is then converted to various inter-mediate products in the presence of specific enzymes. As a result, the potential energy in the glucose molecule is released in steps and eventually used to form ATP. (Please refer to more advanced textbooks for details of the Krebs cycle.) Special membrane proteins in the wall of the mitochondrion—electron carriers—form the electron transport chain that helps with ATP for-mation. The net result of glucose entering the Krebs cy-cle is the formation of carbon dioxide (which is trans-ported to the lungs for exhalation), water, and 36 ATP (only Krebs cycle) or 38 ATP (glycolysis Krebs cycle).

C6H12O6 (Glucose)+ 6 O2 (Oxygen)+ 36 ADP or

38 ADP +36 P or 38 P (phosphate group) → 6

CO2 (Carbon dioxide) +6 H2O (Water)+ 36 ATP or 38 ATP

Glycolysis, Krebs cycle, and electron transport chain are sufficient to provide the cell with all the re-quired ATP. Because the Krebs cycle and electron transport chain require oxygen, it is difficult for the cell to perform its functions in the absence of oxygen.

Not all glucose is broken down. Some glucose mol-ecules may undergo anabolism. In cells such as he-patocytes and muscle, glucose is converted to the storage form of glycogen (glycogenesis). When glu-cose is required, glycogen is broken down to glucose (glycogenolysis). When the glucose supply is low, it may be formed by the breakdown of protein and triglycerides in a process known as gluconeogene-sis. Gluconeogenesis is stimulated by cortisol and glucagon.

LIPID METABOLISM

Because lipids are not water-soluble, they are trans-ported in the blood by combining with protein parti-cles in the blood and are called lipoproteins. Lipoproteins are spherical structures that contain molecules of triglycerides. There are different types of lipoproteins—chylomicron, low-density lipopro-tein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). Chylomi-crons are formed in the gut and absorbed through the lymph before entering the veins. On reaching tissue, fatty acid is released from the triglycerides by the ac-tion of the enzyme lipase in tissue. VLDL transport triglycerides from the hepatocytes to the adipose tis-sue for storage. VLDLs are converted to LDL after the triglycerides are removed by adipose tissue.

LDLs transport triglycerides to the tissues for cell membrane repair and synthesis of bile salts and steroid hormones. It carries most of the total choles-terol in blood. If present in large amounts, LDL de-posits in the blood vessels walls to form fatty plaques that predispose individuals to coronary artery dis-ease, thrombus formation, and stroke. That is why LDL is known as “bad” cholesterol.

HDL transports the excess cholesterol from body cells to the liver for elimination. Because they inhibit the accumulation of cholesterol in the blood, they de-crease the risk of plaque formation; hence, HDL is also known as “good” cholesterol.

The lipids absorbed through the gut may be broken down (lipolysis) and converted to ATP; stored in the adipose tissue and liver (lipogenesis); or used to form other products, such as bile salts, lipoproteins, phos-pholipids in cell membrane, steroid hormones, and myelin sheath. When lipolysis occurs, triglycerides are converted to fatty acids and glycerol before form-ing intermediary products that form ATP. During fatty acid catabolism, acetoacetic acid, ß-hydroxybutyric acid, and acetone are formed. These three products, known as ketone bodies, easily diffuse out of the cells and enter the bloodstream. Certain cells, such as cardiac muscle cells and kidney cells, use ketone bod-ies to form ATP.

PROTEIN METABOLISM

The proteins absorbed in the gut are in the form of amino acids. They are carried by the portal vein to the liver and other tissue where they may be con-verted to ATP, used to form proteins, or converted to glucose (gluconeogenesis) or triglycerides (lipogene-sis). During protein catabolism, one reaction involves removal of the NH2 group of the amino acid (deami-nation) and formation of ammonia. Ammonia is con-verted to urea in the liver and excreted in the urine. For gluconeogenesis to take place, the different amino acids are converted to various intermediate products that can enter the Krebs cycle.

Amino acids are linked by peptide bonds in spe-cific sequences to form new proteins. This occurs in the ribosomes of cells. The sequence of amino acids to form new proteins is dictated by DNA and RNA. Protein synthesis is stimulated by hormones such as growth hormone, thyroid hormone, insulin, estrogen, testosterone, and insulinlike growth factor.