Watch this space for future rants on the regulation of metabolism, high fructose corn syrup, nutritional genomics, and the generally random thoughts that pop into my brain concerning the control of metabolism
Exploring the chemistry of food and your body
Watch this space for future rants on the regulation of metabolism, high fructose corn syrup, nutritional genomics, and the generally random thoughts that pop into my brain concerning the control of metabolism
The phrase, “the body makes perfect sense” has been reiterated throughout the semester, but this unit it really all comes together. The ways in which the body acquires and harvests molecules for energy is brilliant and is in part, intuitive. Yet, all pathways do place and emphasis on the role and importance of acetyl CoA, in metabolism throughout the body.
The fed state (absorptive state) happens when our bodies are digesting food and absorbing its nutrients in our intestines. The raised glucose levels in this state could trigger the release of insulin from the pancreas. At the moment of putting food into our mouth, digestion starts.
INSULIN is the major anabolic hormone in the “fed state”. It’s a polypeptide, released from β-cells in the pancreas in response to ingestion of carbohydrates. Insulin stimulates uptake of glucose in the adipose and muscle tissue – GLUT 4. It helps regulate the levels of glucose in the blood so they are not too high. Insulin also is responsible for the stimulation of LPL or lipoprotein lipase, and the storage of glc as glycogen triacylglycerol. Finally, it promotes the synthesis of protein and growth of cells.
Sorbitol is a sugar alcohol found in many zero-sugar products as a sweetener. It’s claimed to be 60% as sweet as sucrose with 1/3 fewer calories. It’s a naturally occurring substance in berries, has a long shelf-life, and has GRAS status. Sorbitol is not as well absorbed as glucose and other sugars, and ends up converted to fructose by succinate dehydrogenase and sorbitol dehydrogenase. Fructose gets broken down to G-3-P, further resulting in pyruvate. Pyruvate can then potentially enter the Krebs Cycle, get converted to glucose, and/or go through lactate/pyruvate dehydrogenase.
There are three steps of catabolism. Hydrolysis occurs to turn complex molecules into building blocks. Proteins break down into amino acids. Polysaccharides break down to monosaccharides. Triacylglycerols break down to form FFAs and glycerol. Next there is a conversion of building blocks to simpler intermediates (e.g. glucose converts to Acetyl CoA). Finally, there is an oxidation of Acetyl CoA in the citric acid cycle that produces CO2 and ATP and H2O.
Galactose is a monosaccharide that is derived from lactose (milk sugar), and is an isomer of glucose. It is readily taken up by the liver, but there is no way to metabolize it directly, because galactose doesn’t have glucose’s structure (hexokinase cant recognize it). Due to this, galactokinase converts galactose into glucose-1-phosphate. The leloir pathway converts galactose to glucose using 4 enzymes, including UDP.
There are 3 different pathways in which alcohol can be metabolized. The first is alcohol dehydrogenase, which occurs mainly in the liver, and since EtOH can not be stored, this metabolism takes priority. This metabolization requires the NAD to be used up. This is also true for the second pathway, the microsomal ethanol oxidation system. This system is activated when the first is overwhelmed and unable to handle the amount of alcohol that is consumed. As the alcohol is metabolized and NAD has been used up, this product is acetate, which can be turned into acetyl CoA. Due to the lack of NAD, because it was used up during the original metabolization pathways, Acetyl CoA cannot be converted into ATP, and therefore goes into FA synthesis and is turned into triglycerides, which when there is an abundance can create fatty liver and cause liver disease.
There are four general roles of hormones and they have four different rates. They include inducing changes in the membrane (this happens in seconds), regulating catalytic activity of enzymes (happens in minutes), changing the rate of new enzyme synthesis (happens in hours), and changing the rate of cell growth (takes days).
Fructose metabolism
-Fructose undergoes glycolysis faster than glucose does in the liver.
-It bypasses phosphofructokinase and allows fructose to go through liver metabolism. It can lead to an increased fatty acid synthesis, TAG synthesis and VLDL release.
fructose–> fructose-1-phosphate
-doesn’t work on glucose, and not under hormonal (insulin) control
Nonsteroidal hormones:
– Cannot penetrate plasma membrane
– Water soluble
– Bind to receptors on target cell membranes
– Work thru second messenger systems to activate existing enzymes
– Faster action than steroid hormones, action lasts seconds to minutes
– Phosphorylation activates some and inactivates other enzymes
Glucagon is a hormone that is released by the pancreas and targets the liver. It is released when the body is in a fast state. Glucagon tells the body to release fuel from storage (glycogen, TAG and muscle breakdown). Glucagon signals as a first messenger in fixed receptor cascade. It then activates adenylate cyclase, which creates cAMP and sends signals a signal cascade from there.
Anabolism:
1. combine small molecules to form complex molecules
2. requires input of energy
3. regulated differently than catabolic pathways
4. often need reducing power in the form of NADPH
4. divergent process
Starvation State
When the body enters the starvation state after food still hasn’t been consumed after the fasting state, there is a switch from gluconeogenesis to lipolysis to spare proteins from being broken down. Instead, more ketone bodies are synthesized meaning more acetyl CoA enters the TCA cycle than usual. The brain, heart, and skeletal muscle will demand less glucose since they will adapt to the ketone bodies. As a result, less proteins are broken down to provide precursors for gluconeogenesis. However, if food is not consumed soon, we can enter ketoacidosis which breaks down fat and builds up acids which can be life-threatening.
Catabolism
It serves to capture chemical energy from the degradation of energy-rich molecules. Also allows molecules in the diet to be broken down into building blocks needed for synthesis of complex molecules in the body. It’s a convergent process, meaning that a wide variety of molecules are transformed into a few common end products (mostly CO2, H2O, ATP, NH3). Involves 3 steps: Hydrolysis of complex molecules into building blocks, conversion of building blocks to simpler intermediates, and oxidation of acetyl CoA.
Acetaldehyde toxicity is when both detoxification systems produce acetaldehyde which can impair activity and attach to proteins. Has been thought to lead to the start of cirrhosis, the scarring of the liver caused by long-term liver damage. Acetaldehyde on the liver has been thought to cause this damage.
Steroidal hormones are hormones derived from cholesterol that have different functions. These functions include crossing the lipid bilayer, bonding to cytoplasmic receptors, and transportation to the nucleus. Steroid hormones are important for things such as growth, energy metabolism, and reproduction.
Fixed receptor: a protein or amine hormone binds to the receptor on the cell membrane which sends its message via a secondary messenger (like a GPCR).
Mobile receptor: A steroid or thyroid hormone that is able to cross the membrane and act on the hormone receptor complex inside the nucleus of the cell. This acts on gene expression.
Fasting state
In early fasting state which is the first 3-18 hours where our bodies don’t get any dietary energy sources. In this early state, insulin rate is going down while glycogen goes up. Glycogenolysis, gluconeogenesis, and FA synthesis are the main pathways that contribute for energy production. Glycogen would be depleted when it’s been more than 18 hours since we last eat, gluconeogenesis becomes more important, with ketogenesis started to contribute for energy production.
metabolic pathways are generally two types
– catabolic pathways: release energy by breaking down complex molecules to simpler compounds
– anabolic pathways consume energy to build complicated molecules rom simpler ones
metabolic reactions may be coupled, so that energy released from a catabolic reaction can be used to drive an anabolic one
Situations of high ketogenesis:
Fasting:
– Total or serious degree of negative energy balance
Diabetes mellitus:
– Untreated/undiagnosed, uncontrolled
High fat ketogenic diet for epileptic seizures:
– Energy level is adequate to support the growth of children
High fat/low CHO diet for weight reduction
– Energy level is inadequate
Metabolic Effects: Insulin and the Specific Enzyme
When glucose in the muscle increase— glucose transporter increases.
Increasing glucose in the liver— increases glucokinase.
Increasing glycogen synthesis in the liver and mucsle— glycogen synthase increase.
Decreasing glycogen breakdown in the liver and muscle— decreases glycogen phosphorylase
When glycolysis & acetyl-CoA production in the liver and muscle increases— Both phosphofructokinase-1 AND pyruvate dehydrogenase complex increase.
Increased fatty acid synthesis in the liver— increases acetyl-CoA carboxylase.
It is important to link how insulin works and the specific enzymes involved.
Vitamin definitions are often associated with high levels of alcohol intake. The liver is a major storage facility and converter of certain vitamins into their active form. Folic acid is the most common vitamin deficiency because the increased demand in nucleic acids to needed to regenerate injured liver cells. Other vitamin deficiencies include Thiamin, Nicotinic acid, vitamin K, and Vitamin B12.
Type 1 muscle, also known as slow twitch muscle, has lots of mitochondria, use fat as their primary source of fuel, and need oxygen in order to operate (aerobic). They appear red since they have myoglobin. Slow twitch muscles have less muscle fibers since the mitochondria take up space.
Type 2a muscles are “intermediate” muscles since they are both aerobic and anaerobic in nature. Type 2a muscles utilize glucose and fat for fuel.
Type 2b muscles, also known as fast twitch muscles have few mitochondria and are highly glycosidic. They are anaerobic in nature and fatigue fast. They appear white since they do not have lots of myoglobin or mitochondria. Fast twitch muscles have more muscle fibers since there are less mitochondria taking up space.
In a state of starvation, when oxaloacetate is depleted, ketogenesis occurs in the liver. This depletion is due to various factors:
-Pyruvate is unable to undergo carboxylation:
—>there is less glucose available to run through glycolysis and create pyruvate or lactate
—>the proteins are being spared so alanine does not undergo transamination to pyruvate
-A lot of oxaloacetate is used for gluconeogenesis
When there is limited oxaloacetate, the TCA cycle will not occur. But there is still excess Acetyl CoA coming in from Fatty acid B-oxidation. Acetyl CoA build up in the liver and are used to make ketone bodies. Ketone bodies can then be utilized in other organs such as muscle and brain for energy.