Understanding Energy: Carbohydrate Storage
In tandem with our cognitive faculties, the ability of our species to deftly store energy likely led to our enduring success. Our ancestors could rely on their stores of fat to weather periods of starvation and cold environments, allowing them to survive and bear the next generation.
For the vast majority of Western populations, there are now few periods of scarcity. Our inherent needs for sustenance are easily met, driving the formation of excess reserves of energy that serve little biological utility and instead function to our marked detriment.
The series “Understanding Energy” will examine the fundamental biochemical mechanisms underlying energy storage before exploring approaches to promote energy expenditure and maintain energy balance.
All energy we ingest contains calories in the form of carbohydrate, protein, or fat.
One gram of carbohydrate has four calories
One gram of protein has four calories
One gram of fat contains nine calories
The ultimate goal of breaking down these energy forms is creating adenosine triphosphate (ATP), which powers all processes in the body. The most efficient pathway to create ATP is the tripartite of glycolysis, the Krebs cycle, and oxidative phosphorylation, together referred to as aerobic metabolism or aerobic respiration.
Glycolysis and the Krebs cycle directly produce four molecules of ATP without the use of oxygen (i.e., anaerobically), but their real value comes in forming electron carriers that will drive further ATP creation along the electron transport chain in mitochondria, those putative “powerhouses of the cell.” In total, around 30-32 molecules of ATP will be produced from a single molecule of glucose in aerobic metabolism.
Carbohydrates
Simple carbohydrates have only one to two linked molecules of sugar
Glucose and fructose are among the most common monosaccharides
Sucrose (one glucose + one fructose) is the most common disaccharide
Extracted from sugar cane and sugar beet
Found in table sugar and constitutes most added sugar to processed food items
Lactose (one glucose + one galactose) is a common disaccharide found in dairy products
Complex carbohydrates have multiple linked sugar molecules
Starch is the most common complex carbohydrate, found in virtually all plants, and is composed mainly of linked glucose molecules
Fiber cannot be immediately metabolized for energy production or storage and is instead fermented by the microbiome or remains in the digestive tract and aids in bulking stool
If not already in the form of glucose, nearly all dietary carbohydrates (including starches) are metabolized into glucose with a phosphate group attached, which takes places in nearly every cell of the body. (When a phosphate group is added to a molecule, it becomes “phosphorylated.”)
This phosphorylated glucose molecule has three potential outcomes:
Enter glycolysis for creation of ATP
This can occur with oxygen (high yield of ATP) or without oxygen (low yield).
Storage as glycogen (the storage form of glucose) if there is already abundant ATP
Enter glycolysis to form precursor molecules that are converted to triglycerides (the storage form of fat created through a process called lipogenesis) instead of ATP
Glucose is preferentially converted to glycogen instead of triglycerides. Once glycogen stores are saturated, leftover glucose is converted to triglycerides.
Fructose: a special case
Whereas non-fructose carbohydrates are broken down almost everywhere in the body, the liver had long been held to be the exclusive site of fructose metabolism. Recent work suggests the small intestine is instead the primary location for its metabolism.
According to these data, once the ability of the small intestine to break down fructose is saturated, the liver takes over as the primary site for metabolism. Whether in the small intestine or the liver, fructose is also phosphorylated. There are similarly three pathways for this phosphorylated fructose:
Enter glycolysis for creation of ATP
Storage as glycogen if there is already abundant ATP
Fructose must first be converted to glucose before conversion to glycogen.
Enter glycolysis to form precursor molecules for triglycerides
Another forthcoming piece will explore the mechanisms through which fructose drives the development of fat accumulation, diabetes, and fatty liver disease, estimated to affect more then 32% of the global adult population. As many as 40% of individuals with fatty liver disease notably do not have obesity.
On average, just four grams of glucose— the equivalent of a single teaspoon of table sugar— circulates in the blood of a metabolically healthy individual. Although fructose is also found in blood, glucose predominates. The lay term “blood sugar” refers only to “blood glucose” and will be used interchangeable.
When blood sugar rises above four grams (roughly 80mg/dL), insulin is released from the pancreas, prompting the liver, skeletal muscle, and fat (adipose) tissue to absorb glucose from the blood through special membrane channels.
All other cells absorb glucose through membrane channels independently of insulin. The liver possesses a variety of glucose channels that function both with and without insulin— in the presence of insulin, the liver can absorb a greater amount of glucose.
Once immediate energy needs are met, glucose is first stored as glycogen primarily in the liver and skeletal muscle. In total, the liver can store about 100 grams of glycogen (10% of the liver’s overall weight) and muscles store 400 to 500 grams. Glycogen particles in the liver are a full order of magnitude larger than those found in muscle, each containing as many as 50,000 molecules of glucose.
The liver’s cache of glycogen is constantly broken down to keep blood glucose finely tuned between 70 to 100 mg/dL. Skeletal muscle is comparatively greedy and does not contribute its own stores of glycogen to stabilize blood sugar.
Glycogen stored in muscle is broken down during exercise, limiting the need to retrieve glucose from circulation. Notably, when skeletal muscle does require additional glucose to fuel energy production during physical exertion, it can absorb blood glucose independently of insulin, a powerful mechanism for blood sugar regulation in states of insulin resistance.
Taken together, these 600 grams of glycogen constitute 2400 calories, more than enough energy for a typical day. Although this stockpile is vital to the stability of blood glucose and performing exercise, glycogen represents just four per cent of overall energy storage.
Insulin also stimulates adipose tissue to absorb glucose. The vast majority of this glucose is converted into triglycerides and only a small amount is turned into glycogen.
Once the liver and muscles are saturated with glycogen, excess blood glucose is likewise converted into triglycerides by the liver and adipose tissue.
Triglycerides formed in the liver are released into the blood attached to a carrier molecule called VLDL (very low-density lipoprotein) to be delivered to other cells. High levels of VLDL, along with its cousin LDL, contribute to the development of atherosclerotic plaques in arteries.
Great refresher of biology but also a brief treatise of some of the molecular reasons of why we have/are becoming an obese nation - it’s good to be reminded/our own worse enemy