Metabolic Integration, Adaptation and Disease Flashcards
Metabolic Integration
Coordinated regulation and interaction of various metabolic pathways to ensure a constant supply of energy and building blocks for cells and tissues, maintaining homeostasis
Metabolic Integration
Anaerobic metabolism occurs in the cytosol of the muscle cells.A small amount of ATP is produced in the cytosol without the presence of oxygen.Anaerobic metabolism uses glucose as its only source of fueland produces pyruvate and lactic acid. Pyruvate can then be used as fuel for aerobic metabolism.Aerobic metabolism takes place in mitochondria of the cell and is able to use carbohydrates, protein, or fat as fuel sources. Aerobic metabolism is a much slower process than anaerobic metabolism, but it can produce much more ATP and is the process by which the majority of the ATP in the body is generated.
Glycolysis
glucose oxidation in order to obtain ATP
Krebs Cycle
acetyl-CoA oxidation in order to obtain GTP and valuable intermediates.
oxidative phosphorylation
disposal of the electrons released by glycolysis and citric acid cycle. Much of the energy released in this process can be stored as ATP
pentose phosphate pathway
synthesis of pentoses and release of the reducing power needed for anabolic reactions
urea cycle
disposal of NH4+ in less toxic forms
fatty acid β-oxidation
fatty acids breakdown into acetyl-CoA, to be used by the Krebs’ cycle.
gluconeogenesis
- glucose synthesis from smaller precursors, to be used by the brain
Dental Adaptions
Dentition, an animal’s assortment of teeth, is one example of structural variation reflecting diet. The evolutionary adaptation of teeth for processing different kinds of food is one of the major reasons mammals have been so successful. Nonmammalian vertebrates generally have less specialized dentition, but there are interesting exceptions. For example, poisonous snakes, such as rattlesnakes, have fangs, modified teeth that inject venom into prey. Some fangs are hollow, like syringes, whereas others drip the poison along grooves on the surfaces of the teeth. Other teeth are absent. Combined with an elastic ligament that permits the mouth to open very wide, these anatomical adaptations allow prey to be swallowed whole
Stomach & Intestinal adaptions
Evolutionary adaptations to differences in diet are sometimes apparent as variations in the dimensions of digestive organs. For example, large, expandable stomachs are common in carnivorous vertebrates, which may wait a long time between meals and must eat as much as they can when they do catch prey. An expandable stomach enables a rock python to ingest a whole gazelle and a 200-kg African lion to consume 40 kg of meat in one meal! Adaptation is also apparent in the length of the digestive system in different vertebrates. In general, herbivores and omnivores have longer alimentary canals relative to their body size than do carnivores. Plant matter is more difficult to digest than meat because it contains cell walls. A longer digestive tract furnishes more time for digestion and more surface area for the absorption of nutrients. As an example, consider the coyote and koala. Although these two mammals are about the same size, the koala’s intestines are much longer, enhancing the processing of fibrous, protein poor eucalyptus leaves from which the koala obtains nearly all of its nutrients and water.
Koala – enlarged cecum -> mutualistic bacteria ferment finely shredded eucalyptus
The cecum connects the small intestine to the colon.
The main functions of the cecum areto absorb fluids and salts that remain after completion of intestinal digestion and absorption and to mix its contents with a lubricating substance, mucus.
In rabbits and some rodents, mutualistic bacteria live in the large intestine as well as in the cecum. Since most nutrients are absorbed in the small intestine, nourishing byproducts of fermentation by bacteria in the large intestine are initially lost with the faeces. Rabbits and rodents recover these nutrients by coprophagy (from the Greek, meaning “dung eating”), feeding on some of their feces and then passing the food through the alimentary canal a second time. The familiar rabbit “pellets,” which are not reingested, are the faeces eliminated after food has passed through the digestive tract twice.
During the first few steps of exercise
your muscles are the first to respond to the change in activity level. Your lungs and heart do not react as quickly, and during those beginning steps, they can’t yet increase the delivery of oxygen. In order for our bodies to get the energy that is needed in these beginning steps, the muscles rely on a small amount of ATP that is stored in resting muscles. The stored ATP is able to provide energy for only a few seconds before it is depleted. Once the stored ATP is just about used up, the body resorts to another high-energy molecule known as creatine phosphate to convert ADP (adenosine diphosphate) to ATP. After about 10 seconds, the stored creatine phosphate in the muscle cells is also depleted as well.
Exercise
Intense exercise lasting seconds: or during intermittent exercise, most ATP is derived from the breakdown of phosphocreatine (PCr) and glycogen to lactate.
The muscle ATP concentration is reasonably well maintained, although it may decrease by ~20% during very intense exercise.
> 1 min of exercise: (e.g. 800m track event), oxidative phosphorylation is the major ATP-generating pathway, and intramuscular
The fuel sources for anaerobic and aerobic metabolism will change depending on the amount of nutrients available and the type of metabolism.
Glucosemay come from blood glucose (which is from dietary carbohydrates, liver glycogen, and glucose synthesis) or muscle glycogen. Glucose is the primary energy source for both anaerobic and aerobic metabolism.
Fatty acidsare stored as triglycerides in muscles, but about 90 percent of stored energy is found in adipose tissue. As low- to moderate-intensity exercise continues using aerobic metabolism, fatty acids become the predominant fuel source for exercising muscles.
Althoughproteinis not considered a major energy source, small amounts of amino acids are used while resting or doing an activity. The amount of amino acids used for energy metabolism increases if the total energy intake from your diet does not meet your nutrient needs or if you are involved in long endurance exercise. When amino acids are broken down and the nitrogen-containing amine group is removed, the remaining carbon molecule can be broken down into ATP via aerobic metabolism, or it can be used to make glucose. When exercise continues for many hours, amino acid use will increase as an energy source and for glucose synthesis.
During events lasting several minutes to hours, the oxidative metabolism of carbohydrate and fat provides almost all the ATP for contracting skeletal muscle.
The major intramuscular and extramuscular substrates are muscle glycogen, blood glucose (derived from liver glycogenolysis and gluconeogenesis, and from the gut when carbohydrate is ingested) and fatty acids derived from both muscle (intramuscular triglyceride (IMTG)) and adipose tissue triglyceride stores.
Muscle contains limited ATP
Muscle contains reservoir of creatine phosphate
Creatine P + ADP Creatine + ATP
Creatine kinase
Sprint uses ATP, creatine phosphate & glycolysis (of stored glycogen)
Pace unsustainable because exhaustion of:
(i) creatine phosphate
(ii) NAD+
Excess lactic acid is also produced
Marathon running - insufficient glycogen stores
FA breakdown essential
Efficient use of FAs & glycogen improves speed
Excerise Continued
Carbohydrate oxidation, particularly from muscle glycogen, dominates at higher exercise intensities, whereas fat oxidation is more important at lower intensities. Maximal rates of fat oxidation occur at ~60–65% VO2max
Under conditions of low carbohydrate availability, the contribution from amino acid metabolism is increased
Intensity
During low-intensity activities = aerobic metabolismover anaerobic metabolism
More efficient and produces larger amounts of ATP.
What does it mean?
The fat-burning zone = low-intensity aerobic activity
Cardio zone = high-intensity aerobic
Bird Migration
Birds store large amounts of fat (adipose tissue) to fuel long-distance flights, as fat is a highly energy-dense and lightweight fuel source.
Glycogen stores are small
Migratory birds often “beef up” before long flights, increasing their fat stores, and some species can store up to 50-60% of their body mass as fat.
Hibernation
Hibernation is a prolonged, deep state of torpor, while torpor is a shorter-term, less intense state of reduced activity and metabolism
Used by animals to conserve energy, especially during harsh condition
Eat significantly more before the winter months, bulking up on fat
Heart rate and breathing slows down, body temperature decreases
Metabolic rate can be as low as 1–5%
Decrease of up to 77-107% ATP turnover compared to active periods
Glycogen Storage Diseases
A group of inherited metabolic disorders that disrupt the body’s ability to store or utilize glycogen
At least 9 types of GSD
Grouped by the enzyme that is missing in each one.
Each GSD has its own symptoms and needs different treatment.
Von Gierke’s Disease
Hepatomegaly = enlarged liver
2 major subtypes, GSD Ia and GSD Ib
GSD Ia: there is a deficiency of enzyme glucose-6-phosphatase
GSD 1b: deficiency of the transporter enzyme, glucose-6-phosphate translocase (G6PT).
Deficiency of either causes an accumulation of glycogen and fat in the liver, kidney, and intestinal mucosa
GSD I in the overall population is 1/100,000 with GSD Ia and Ib prevalent in 80% and 20% respectively.
In addition, patients with GSD Ib present with recurrent bacterial infections due to neutropenia (too few neutrophils).
GSD Ia results from mutations in theG6PCgene on chromosome 17q21 that encodes for the G6Pase-a catalytic subunit. GSD Ib results from mutations in theSLC37A4gene on chromosome 11q23.3.
The availability of gene sequencing makes liver biopsy unnecessary. However, a biopsy may be ordered by the gastroenterologist in view of hepatomegaly. Histological evaluation of the liver shows hepatocytes filled with glycogen that is periodic acid-Schiff positive and diastase sensitive.
Initial laboratory findings in patients with GSD I will show hypoglycemia, lactic acidosis, hyperuricemia, hypercholesterolemia, and hypertriglyceridemia. Besides these, patients with GSD Ib will have neutropenia ranging from mild to complete agranulocytosis.Instead of the invasive liver biopsy, noninvasive molecular genetic testing that includes full gene sequencing ofG6PC(GSD Ia) andSLC37A4(GSD Ib) genes is preferred for confirming the diagnosis.
Von Gierke’s Disease Mechanism
2 major subtypes, GSD Ia and GSD Ib
GSD Ia: deficiency of enzyme glucose-6-phosphatase (G6Pase) which cleaves glycogen to glucose thus leading to hypoglycemia and lactic acidosis.
GSD 1b: normal G6Pase enzyme activity but have a deficiency of the transporter enzyme, glucose-6-phosphate translocase (G6PT).
Von Gierke’s Disease Treatment
Historically, the prognosis for untreated individuals with GSD I was poor, with many dying at a young age.
Early diagnosis and treatment have significantly improved the prognosis, with most individuals now surviving into adulthood
Small, frequent feedings during the day
Uncooked cornstarch mixed in water, Cornstarch is digested slowly, so it provides a steady release of glucose in between feedings.
Overnight tube feeding, typically via a naso-gastric tube.
McArdle’s Disease
Type 5
Primarily affects skeletal muscles
Deficiency of the enzyme muscle muscle glycogen phosphorylase (myophosphorylase)
1951 First disease report
1959 enzyme responsible discovered
1984 gene was first discovered
1 in 50,000 - 200,000
Most cases present in the second or third decade of life.
McArdle’s Disease Symptoms
Muscle-specific isoform of the glycogen phosphorylase enzyme
the absence of myophosphorylase leads to the accumulation of glycogen in muscle tissues, as it cannot be adequately broken down to release glucose.
Exercise intolerance, muscle cramps, and fatigue
