1. Introduction
Understanding where, and how the energy that enables life to exist comes from, known as energy metabolism (Cox and Nelson 2013), is integral to understanding health and nutrient needs for organisms. The study of energy metabolism is applicable in many areas; medicine and agricultural livestock health and production are two major applications for this discipline of study. There are different forms of energy metabolism throughout organisms on this planet, however many share the same basic cycles and functions at a metabolic rate. For example, a practically universal central pathway for the metabolism of glucose is glycolysis; the break down of glucose to attain metabolic energy to do biological work (Cox and Nelson 2013). Energy is obtained by harvesting the energy trapped in chemical bonds of food molecules (nutrients). Depending on the nutrient type an organism consumes, the energy metabolism pathways alter slightly. The major constituents of food are carbohydrates, lipids and proteins (Da Poian et al. 2010). This discussion paper will look at the energy metabolism of the Canis familiaris’ (dog) energy metabolism and regulation.
2. Diet, digestion and absorption
The dog is a carnivore and consumes a diet consisting mainly of fat and protein with a small amount of carbohydrates (Edwards et al. 2011). The digestive tract of the dog is relatively simple compared to herbivores, the stomach and small intestine are the main digestion area’s for the dog, the stomach expands to temporarily store a large amount of food to accommodate for it’s large meal sizes (Edwards et al. 2011). Nutrients (e.g. meat) is consumed via the mouth making use of the canine teeth to rip apart the flesh, this is mixed with saliva that is used as a lubricant, the food is then passed down the oesophagus to the stomach via a series of rhythmic contractions known as peristalsis (Eldredge and Giffin 2007). The food in the stomach can remain there for up to 8 hours in which then passes through the pylorus (opening from the stomach to the duodenum/small intestine) into the duodenum and rest of the small intestine (Eldredge and Giffin 2007). The food is broken down into smaller pieces via digestive juices from the pancreas and small intestine (Cox and Nelson 2013). Fats are broken down to monoacylglycerols and long-chain fatty acids, proteins are broken down to amino acids and small peptides, and carbohydrates are broken down to monosaccharides (mainly glucose) (Da Poian et al. 2010) These products of food digestion are absorbed through the intestinal mucosa (epithelial mucosa) of the villi that line the small intestine. Amino acids, peptides and monosaccharides (glucose) are absorbed into the capillaries, the monoacylglycerol and long chain fatty acids are absorbed into the lymphatic system (Cox and Nelson 2013, Da Poian et al. 2010). Any undigested food and fibre move through the small intestine into the colon where this waste material is stored and excreted as faeces (Eldredge and Giffin 2007).
2.1. Fat breakdown
Ingested dietary fats are converted from insoluble macroscopic fats to microscopic micelles to allow absorption through the intestinal wall (Cox and Nelson 2013). This is achieved through the action of bile salts, which emulsify them in the small intestine forming mixed micelles, and intestinal lipases then hydrolyse (degrade) them. This then allows the fats to be in a form that can be absorbed by intestinal epithelial cells and then reconverted back to triacylglycerols. In this process, the fats are incorporated into chylomicrons, which move through the lymphatic system and then into the blood stream to muscle and adipose tissues. In the muscles, the fats are oxidised for energy whereas in the adipose tissues they are stored as triacylglycerols (Cox and Nelson 2013).
2.2. Protein breakdown
The protein obtained from food is enzymatically degraded to amino acids via proteases in the stomach and small intestine (Cox and Nelson 2013). Enzymes involved in the breakdown of protein to amino acids are trypsin, pepsin and chymotrypsin and other intestinal peptidases (Cox and Nelson 2013) The subsequent concoction of free amino acids is moved into the epithelial cells in the intestinal wall where they are absorbed into the blood stream and transported to the liver (Cox and Nelson 2013). Some proteins are not completely hydrolysed in the gastrointestinal tract.
2.3. Carbohydrate breakdown
Carbohydrates obtained from food are degraded by enzymes; amylase, maltase, sucrose and lactase (Cox and Nelson). Once these enzymes have degraded the carbohydrates down to monosaccharides (glucose), they are absorbed through the intestinal wall into the blood stream and transported to major organs, in particular the brain, muscle and liver (Cox and Nelson).
3. Energy sources of major organs
3.1. Heart
3.2. Brain
Glucose is the main fuel for the brain; it is transported into the brain cells via the glucose transporter GLUT3 (Cox and Nelson 2013). The brain does not have it’s own fuel stores and so requires a continued supply of glucose for it’s biological functions. During starvation or extreme circumstances however, when glucose supply is unavailable, or partially unavailable, ketone bodies produced by the liver from free fatty acids can be used (Cox and Nelson). The brain cannot use fatty acids as fuel because they are unable to cross the blood-brain barrier, which has to do with the exchange of solutes between the brain extracellular fluid and blood plasma (Oldendorf 1977).
3.3. Muscle
The muscles major fuels are glucose and fatty acids, transported via the blood stream (Cox and Nelson 2013)
3.4. Liver
Most nutrients absorbed from the intestine are bought to the liver via the blood stream, where the liver performs the main metabolic activities to provide fuel for the brain muscles and other organs (Cox and Nelson 2013)
4. Glycogen
When there is excess glucose available it is converted into glycogen stored mainly in muscles and the liver, muscle glycogen stores are used rapidly whilst liver glycogen stores last longer, used for situations such as fasting (i.e. sleeping) when dietary glucose is unavailable (Cox and Nelson 2013).
5. Biochemical pathways for metabolism
The way that organism’s cells acquire and consume energy for biological work integral for life is known as energy metabolism (Da Poian et al. 2010). The energy released when the bonds are broken from nutrient molecules is caught and synthesised into high-energy molecules, ATP (Adenosine triphosphate) is the main energy molecule in cells (Da Poian et al. 2010).
5.1. Pathways of nutrient degradation
Glucose undergoes glycolysis, fatty acids undergo the fatty acid oxidation pathway and amino acids undergo the amino acid transamination/deamination pathway. All of which feed into the citric acid cycle for further oxidation (Da Poian et al. 2010).
Glycolysis
Glycolysis is a metabolic pathway that occurs in the cytoplasm of the cell. One glucose (6C) molecule is degraded through a series of enzymatic pathways to produce two pyruvate (3C) molecules.
Below is a diagram illustrating this pathway. There are two phases in glycolysis; the preparatory phase where ATP is spent to supply energy for the breakdown of glucose, and the pay off phase, which involves energy capture from oxidation reaction in the form of 2 ATP and 1 NADH. The net equation for the process is:
Figure 1. The Glycolytic Pathway (Da Poian et al. 2010)
After glycolysis the pyruvate molecules can take one of two pathways. Fermentation, an anaerobic process that results in lactic acid (in the case of dogs) and replenishes NAD+, or into the PDC (pyruvate dehydrogenase complex) which breaks down the pyruvate into acetyl-CoA ready to go into the Citric acid cycle for further breakdown (Da Poian et al. 2010)
The metabolisation of pyruvate via fermentation (anaerobic) yields a low 2ATP per glucose molecule compared to the aerobic breakdown of glucose which results in 32ATP after going through the TCA (Tricarboxylic Acid) cycle and Electron Transport Chain. Fermentation is important for reforming NAD+ to go into glycolysis (Cox and Nelson 2013).
Figure 2. PDC and fermentation pathways (Cox and Nelson 2013)
Gluconeogenesis
Gluconeogenesis is the process by which pyruvate and related 3- and 4- carbon molecules are converted to glucose.
Glucose follows the same basic pathway as glycolysis but in the reverse direction, with the exception of three irreversible steps that are bypassed via separate enzymes. Gluconeogenesis is performed mainly in the liver, and at the cellular level it takes place mostly in the cytosol.
Gluconeogenesis is a means of maintaining blood glucose levels. It is used especially during intensive exercise, fasting or starvation (Cox and Nelson 2013).
Figure 3. The Gluconeogenesis pathway (Cox and Nelson 2013)
Fatty acid breakdown
Fatty acid oxidation is a three-stage process. Stage 1. β oxidation: two-carbon units are detached progressively from a fatty acid chain, being oxidised yielding acetyl-CoA. Stage 2. The acetyl-CoA then enters the TCA cycle and are oxidised to CO2. Stage 3. Electrons from both stage 1 and 2 enter the ETC (Electron Transport Chain) for oxidative phosphorylation (Da Poian et al. 2010)
Figure 4. Stages of Fatty acid oxidation (Cox and Nelson 2013)
Amino acid breakdown
The process of amino acid breakdown occurs mainly in the liver. Alanine transports the amino groups from muscles and tissues that breakdown amino acids to the liver in a form that is non-toxic, this is known as the glucose-alanine cycle.
Amino acid breakdown is the process by which the amino group is separated from the carbon skeleton. The amino group is moved to α-ketogluterate in which it forms glutamate (the form that the glucose-alanine cycle uses to transport it) This is known as the transamination reaction (Nelson and Cox 2013).
Figure 5. An example of protein catabolism (Cox and Nelson 2013)
Figure 6. Amino acid catabolism (Cox and Nelson 2013) The carbon skeletons are fed into the TCA cycle and the ammonia groups go into the urea cycle where they are excreted as a nitrogen product (Cox and Nelson 2013).
Urea cycle
A cycle that takes place in the liver which synthesizes urea from amino groups and CO2 (Cox and Nelson 2013).
The Citric Acid Cycle
The Citric Acid Cycle, also known as the TCA Cycle (Tricarboxylic Acid Cycle) or Krebs cycle, is the central metabolic degradative pathway. Fats, amino acids and sugars are oxidised to CO2 and H2O via the TCA cycle and Electron Transport Chain. The citric acid cycle occurs in the mitochondria, it is central to energy metabolism as well as providing four and five-carbon intermediates as precursors for a number of other products (Cox and Nelson 2013). Below is a diagram illustrating the steps of the TCA cycle. The TCA cycle ultimately converts citrate to oxaloacetate, and releases CO2. For each Acetyl CoA oxidised it produces (i.e each turn of the cycle) there are 3NADH, 1FADH2, 1ATP (or GTP) and 2 CO2 molecules produced. The TCA cycle is oxygen dependent (Da Poian et al. 2010). Energy from the TCA cycle is conserved from the reduction of NAD+ and FAD to NADH and FADH2, these electrons are then transferred to oxygen through the electron transport chain. The TCA cycle is regulated by concentrations of substrates and products (Cox and Nelson 2013).
Figure 7. The TCA Cycle (Da Poian et al. 2010)
The Electron Transport Chain
The electron transport chain (ETC) couples the reaction between an electron donor and an electron acceptor, this is coupled with transfer of protons across the mitochondrial inner membrane creating a proton gradient and so driving the synthesis of ATP. The ETC is the site of oxidative phosphorylation (Da Poian et al. 2010).
Figure 8. The Electron Transport Chain (Cox and Nelson 2013)
Oxidative Phosphorylation
Oxidative phosphorylation is the transport of electrons from NADH or FADH2 to O2 via protein complexes known as the electron transport chain (ETC) from which the energy is used to drive ATP synthesis (Cox and Nelson 2013).
6. Pathways of nutrient degradation converge on the TCA cycle
Figure 9. Nutrient metabolism pathways (Da Poian et al. 2010)
Figure 10. A basic overview of the energy metabolism pathways (Cox and Nelson 2013, Da Poian et al. 2010)
Regulation
Metabolic regulation is the control of metabolism via the many systems that control metabolic pathway processes. Metabolism is regulated in cells via a variety of mechanisms; metabolic flux rate control is spread amongst enzymes in the metabolic pathway. Hormones regulate action of cells or tissues (Cox and Nelson 2013).
The hormones glucagon and insulin are involved with blood glucose levels, Glucagon increases blood glucose levels by stimulating the conversion of glycogen to glucose through a pathway known as glycogenolysis. Insulin stimulates a decrease in blood glucose levels, that is, converting glucose back to glycogen for storage and so reducing the amount of glucose in the blood. Glycogen is stored predominantly in the liver and muscles, used as a quick energy source for both aerobic and anaerobic metabolism. The hormone epinephrine is involved in increasing metabolic rate, blood glucose concentrations and other body functions, the hormone is a response to stress. The hormone cortisol is involved in fat, protein and carbohydrate metabolism, it is a stress response that stimulates gluconeogenesis to reduce blood glucose levels. Phosphoenolpyruvate Carboxykinase is an enzyme involved in gluconeogenesis that enables the bypass of irreversible reactions within glycolysis. 5’ AMP protein kinase (AMPK) is an enzyme involved in metabolic pathways, it is a stimulus for fatty acid oxidation as well as being involved in ketogenesis. Acetyl-CoA carboxylase is involved in fatty acid synthesis (Cox and Nelson 2013).
The breakdown of nutrient energy to usable chemical energy for biological work is precisely regulated by hormones and concentrations of substrates and products, metabolic pathways are integrated and complicated with different factors controlling the energy regulation and alteration (Da Poian et al. 2010).
Reference
Cox MM, Nelson DL (2013) ‘Lehninger Principles of Biochemistry (sixth edition).’ (W. H. Freeman and Company NY)
Da Poian AT, El-Bacha T, Luz MP (2010) Nutrient Utilization in Humans: Metabolism Pathways. Nature Education 9, 11
