Flashcards in Metabolism 1/2 (handout p. 1-20) Deck (42):
Describe metabolism and its two contrasting processes.
refers to the chemical changes that convert foodstuffs into usable forms of energy and complex biological molecules
Catabolism – breakdown of more complex organic molecules into simpler biological molecules and the release of energy through ATP.
Anabolism – assembly of simpler substances to form new and more complex molecules, which requires the use of ATP and energy.
Describe the formation of ATP and the formation of ADP.
Adenosine triphosphate (ATP) (see above) is a crucial component of metabolism. ATP contains three phosphates held together by high-energy bonds.
Adenosine diphosphate (ADP) is formed
when the third phosphate is cleaved from ATP. Energy is released, which can then drive anabolic
reactions, as well as other reactions in the body (i.e. membrane transport).
Inversely, energy is
needed to add the third phosphate group to ADP in order to form ATP. Therefore, the synthesis of
ATP is an energetically unfavorable phosphorylation reaction in which a phosphate group is added
to ADP. When required, ATP gives up its energy packet though its energetically favorable hydrolysis to ADP and inorganic phosphate.
What do oxidation reactions result in?
Oxidation reactions result in the loss of electron from an atom, as occurs during the addition of
oxygen to a molecule or when hydrogen is removed.
What is reduction?
Reduction is the addition of electron to an atom, as occurs during the addition of hydrogen to a molecule or the removal of oxygen from it.
What are the most important electron carriers? What purpose do they serve?
How do they differ from each other?
NAD+ (nicotinamide adenine dinucleotide) and the closely related NADP+ (nicotinamide adenine
dinucleotide phosphate) are the most important electron carriers.
NADP+ has an additional
phosphate group on the 2’ position of the ribose ring that carries the adenine moiety. NAD+ and
NADP+ are needed as an oxidizing agent.
NADH= reduced form of NAD+
NADPH= reduced form of NADP+
Give an overview metabolism starting with mono, di and polysaccharides.
P 8 on h/o
What is the primary function of acetyl-CoA
Where is it generated? What is it a major source of?
What gives rise to acetyl-CoA?
key molecule, which is used in many biochemical reactions in carbohydrate, protein and lipid metabolism. The primary function of acetyl-CoA is to convey the carbon atoms within the acetyl group to the citric acid cycle (a.k.a Tricarboxylic acid cycle or Krebs
cycle) to be oxidized for energy production.
Acetyl-CoA is generated in the mitochondrial matrix
and is a major source of useful metabolic energy.
It is important to note that all metabolic components (carbohydrates, lipids, proteins) can give rise to
acetyl-CoA, making it a “common fuel” that can enter the CAC and give rise to energy production
What are the fates of Acetyl-CoA?
(4 fates of paths of usage)
p 9 h/o
1) The primary fate is to oxidize acetyl groups in CAC for energy generation. Note: this is a
combustion reaction, and the products are ATP, H20, CO2.
2) Lipogenesis – formation of fatty acids. These fatty acids can then go through esterification to
form Triacylglycerol (a.k.a, triacylglyceride, TAG).
3) Ketogenesis – formation of ketone bodies.
4) Cholesterologenesis – formations of cholesterol, which can then be synthesized into steroids.
Involves the transfer of acetyl units in the cytosol. Therefore, Acetyl-CoA is also a precursor of cholesterol, which is then a precursor of steroids.
Where does the conversion of pyruvate to acetyl CoA take place?
matrix of mitochondria
Why does dietary balance determine whether we gain or lose weight?
All components of metabolism (carbs, proteins, fats) can give rise to the synthesis
and storage of fat by first converting into Acetyl CoA. Therefore, the consumption of calories from all components can lead to the formation of fat. This is why the dietary balance determines whether we gain or lose weight.
Describe the storage and catabolism of dietary carbohydrates.
How are carbohydrates primarily metabolized?
What happens to fructose and galactose?
What happens to excess carbohydrates?
How is glycogen stored? Where are the largest stores?
- Carbohydrates are metabolized primarily via glucose.
- Fructose and galactose are converted to intermediates in the same glycolysis pathway.
- Excess carbohydrates are stored in glycogen.
- There is a limit to how much glycogen we can store.
In the liver, glycogen is stored to be used as glucose by the rest of the body later on.
The liver and skeletal/heart muscle have the largest stores.
Most cells have some storage of glycogen
Describe the storage and catabolism of dietary fatty acids.
How do fatty acids form acetyl-CoA?
If they don't form Acetyl-CoA what do they form instead?
- Fatty acids go through beta-oxidation in the mitochondria to form acetyl-CoA
Therefore, only cells that have mitochondria can have beta-oxidation
- Otherwise, they form triacylglycerols, which are stored in adipose tissue.
The breakdown of TAGs into fatty acids is triggered by a hormonal signal.
Fatty acids are then released.
Describe the storage and catabolism of dietary proteins.
How are amino acids metabolized? What is produced during this process?
How are amino acids stored?
Amino acids can be metabolized to either Acetyl CoA or an intermediate in the citric acid cycle.
This leads to the production of ammonia, which can be toxic at high levels.
- Amino acids are store as proteins.
The preferred fuels are not the same in all cell types.
skeletal muscle at rest
skeletal muscle exertion
heart muscle fatty acids
brain fed state
liver- fatty acids, glucose, aa
adipose tissue- fatty acids
skeletal muscle at rest: fatty acids
skeletal muscle exertion: glucose
heart muscle- fatty acids
brain fed state: glucose
brain starvation: ketone bodies/glucose
The liver expends energy during fasting through the access of fatty acids to make glucose.
The heart will use everything, but it has a preference for fatty acids.
Describe the brain's need for glucose during fed state.
During the fed state, the brain has an absolute need for glucose. If it does not have access
to glucose, nerve cells die in a very short period of time. Therefore, the driving force for the
coordination of metabolism is to provide the normal range of glucose levels for the brain.
In the fasted state, what happens in adipose tissue?
In the fasted state, what occurs in the liver? How is ATP acquired for gluconeogenesis?
In the fasted state (after 3 days of starvation), low blood insulin levels cause the activation of
lipolysis in the adipose tissue, raising the blood levels of fatty acids. These fatty acids are used in preference to glucose by many tissues.
In the fasted state, fatty acid oxidation (beta-oxidation) in the
liver provides most of the ATP needed for gluconeogenesis.
The small amounts of Acetyl CoA generated by fatty acid oxidation in the liver are completely oxidized to form ketone bodies by the
Ketones bodies are released in the blood and are a source of energy for many tissues. The brain starts to use ketone bodies as an alternative fuel when ketone body levels in the blood are high enough. This is caused by an up-regulation of a transporter that gets ketone into the
brain. It is important to note, however, that the brain will never lose its requirement for glucose
During fasting, the small amounts of Acetyl CoA
generated by fatty acid oxidation in the liver are completely oxidized to form ketone bodies by the
liver mitochondria. What are the ketone bodies used for? Where?
Ketones bodies are released in the blood and are a source of energy for many tissues. The brain starts to use ketone bodies as an alternative fuel when ketone body levels in the
blood are high enough. This is caused by an up-regulation of a transporter that gets ketone into the
brain. It is important to note, however, that the brain will never lose its requirement for glucose.
How are small portions of protein stored?
How are carbohydrates and proteins stored?
How are fats stored?
Small portions of protein can be stored as energy.
Carbohydrates and proteins are stored in a hydrated state.
Fats are stored in anhydrous state.
Give the number of kcal per gram of carbohydrates, proteins, and fat.
Describe the following major dietary carbohydrates and the food source they are found in, enzyme, and linkage.
amylose- potatoes rice corn bread
sucrose- table sugar, desserts
lactose- milk, milk products
fructose- fruit, honey
glucose- fruit, honey, grapes
starch- (mixture of amylose and amylopectin)
trehalose- young mushroom
raffinose- leguminous seeds
cellulose- "fiber" in plant foods, not digestible by humans, forms the bulk of the feces
p 14 to check linkages/enzymes!
Describe starch. What is it? What kind of linkages? How is it broken down?
Is pancreatic or salivary amylase more important for digestion?
Starch- most carbohydrates come in as starch, which (as shown) is a polymer composed entirely of
glucose. Starch has a mixture of alpha 1-4 and alpha 1-6 linkages that are broken down by amylase
in the saliva and pancreas. Pancreatic amylase is secreted in large excess relative to starch intake and
is more important for digestion than the salivary enzyme.
What are the major disaccharides? Where are they found?
Discuss sucrase and lactase. Which is found in greater concentration?
Where is final hydrolysis of di and oligosaccharides carried out?
What happens to saccharides that are not hydrolyzed by alpha amylase or intestinal surface enzymes? Where do they end up?
the major disaccharides are sucrose (glucose and fructose) and lactose (galactose
Disaccharidases, found in the brush border of the small intestine, break these down.
Two examples are sucrase and lactase. Sucrase is generally found in great excess. Lactase is
generally in lower concentrations.
Final hydrolysis of di- and oligosaccharides is carried out by
enzymes on the luminal surface of small intestinal epithelial cells.
Saccharides that are not
hydrolyzed by alpha-amylase and/or intestinal surface enzymes cannot be absorbed; therefore they reach
the lower tract of the intestine, which from the lower ileum on contains Bacteria.
Describe lactose intolerance. How might it develop?
What happens in lactose intolerance. Where? What clinical symptoms may manifest?
Lactose intolerance is a genetically determined (can also be caused by environmental factors,
physiological decline due to ageing, or damage to the mucosa) characteristic that results in a deficiency in lactase enzyme production. Over 30 million people are lactose intolerant in the United States alone, and the disorder is particularly prevalent in African American, Asian, and Hispanic populations.
Due to a decreased amount of intestinal lactase, dietary lactose is not sufficiently hydrolyzed
or absorbed. It remains in the intestine, where it causes osmosis of water into the intestine. In
addition, intestinal bacteria metabolize the lactose to produce lactic acid and mixtures of hydrogen,
carbon dioxide, and methane gas. The result is bloating, flatulence, and diarrhea, all of which can be avoided simply by eliminating milk and milk products from the diet.
What produces the lactase enzyme? Where is this gene found? What causes congenital lactase deficiency?
How is this gene affected in lactose intolerance in adults?
The LCT gene is expressed by intestinal epithelia cells and produces the lactase enzyme. At least nine mutations in this gene cause congenital lactase deficiency (congenital alactasia) starting at infancy. These mutations can cause changes in the enzyme’s secondary structure or truncate it abnormally. In adults, lactose intolerance is cause by gradually decreasing activity of the LCT gene.
What is anaphylaxis? How does this differ from lactose intolerance?
Lactose intolerance is not to be confused with anaphylaxis, a milk-induced allergic reaction due to
Secondary lactose intolerance is found in children who have suffered an episode of
Damage to the intestinal lining in the child can lead to a lack of lactase enzyme, resulting in the symptoms mentioned above. This condition, however, is only temporary and gets
better once the gut lining is healed.
Show in a flow chart glycogen to Acetyl Co-A/ TCA cycle.
p 16/slide 18
What is insulin? What type of cells (and from where) secrete it?
What is its major function?
What does it promote?
a peptide hormone, secreted by beta cells of the pancreas that, among other functions, mainly regulates glucose metabolism. Its major function is to maintain low blood glucose levels and counter the function of hyperglycemia-generating hormones.5 Insulin
promotes glycolysis on a long-term basis, as well as glycogen synthesis.
What is glucagon?
What type of cells secrete it? When is it secreted? What is its effect?
a peptide hormone that is secreted by the alpha cells of the pancreas when blood glucose is low (between meals or during exercise). Glucagon causes the liver to release
glucose into the blood.
Define hypo and hyperglycemia.
Hypoglycemia – blood glucose levels below the normal range.
Hyperglycemia – blood glucose levels above the normal range.
What is glycogenolysis?
the breakdown of glycogen to glucose-1-phosphate and glucose in the
liver and in the muscles by the enzyme glycogen phosphorylase
(hypoglycemia – glucagon increases).
What is epinephrine? What secretes it?
Epinephrine is a neurotransmitter and secreted by the medulla of the adrenal glands.
Describe glycolysis. What are the inputs/outputs?
What happens to insulin levels during hyperglycemia?
(“splitting sugars”) is the metabolic pathway that a single glucose molecule
converts into a total of 2 molecules of pyruvic acid, 2 molecules of ATP, 2 molecules of
pyruvic acid, 2 molecules of ATP, 2 molecules of NADH and 2 molecules of water
(hyperglycemia – Insulin increases).
What is gluconeogenesis? What does it result in?
How is glucagon affected in hypoglycemia?
results in generation of glucose from non-carbohydrate carbon substrates
such as pyruvate, lactate, glycerol, and glucogenic amino acids (hypoglycemia – glucagon increases)
Describe glycogenesis. What is it the formation of?
formation of glycogen from glucose (hyperglycemia – Insulin increases)
Describe the importance of maintaining a blood glucose level within a
normal range. (What is the range that must be maintained?)
What can hypo and hyperglycemia cause?
The figure below describes the importance of maintaining a blood glucose level within a
normal range. Hypoglycemia can cause neurological problems, whereas hyperglycemia can cause
type 2 Diabetes Mellitus. It is also important to note that glucose is crucial for the brain to function
properly. The brain uses around 120 grams of glucose per day, whereas muscle tissue uses only 40
p 17/slide 19
acute hypoglycemia causes neurological problems, coma and death. Therefore fasting blood glucose levels must be maintained above 60mg/100mL
chronic hyperglycemia (fasting blood glucose above above 110mg/100mL) causes multiple problems, including increased oxidative stress within cells. Increased intracellular glucose also leads to intracellular lipids and consequent liptoxicity. Ultimately, these stresses induce insulin-resistance and beta cell dysfunction, which further compromise glucose tolerance and lead to T2DM. High levels of blood glucose also create an osmotic burdern on cells and the organism.
How much glucose does the brain and muscle tissue use per day?
The brain uses around 120 grams of glucose per day, whereas muscle tissue uses only 40
Draw and describe the fed state.
What does it result in? How is excess glucose stored
What 2 things can dietary glucose be converted to? By what processes?
Describe the liver's role.
Does the liver engage in gluconeogensis during fed state?
What happens to Aceytl CoA?
Describe the B cells of the pancreas.
p 18, Slide 20-24
Results in energy production; excess glucose is stored as glycogen.
-Dietary glucose can be converted into:
- glycogen by glycogenesis.
- pyruvate and lactate by glycolysis.
-Dietary glucose is also passed through the liver to reach other organs that need glucose to function
(i.e., brain, muscle).
-In the well-fed state, the liver uses glucose and does not engage in gluconeogenesis.
-Pyruvate can be oxidized to acetyl CoA.
-Acetyl CoA can be converted into triacylglycerol or oxidized into carbon dioxide and water by the
-The beta-cells of the pancreas are very responsive to the influx of glucose and amino acids in the fed
state, causing it to release insulin.
Describe and draw the fasted state/starvation.
What happens to glucose levels? What is a main concern?
What is released by alpha cells and adrenal medulla?
What happens to glycogen?
Where does gluconeogensis occur?
What is the pentose phosphate pathway? What results and is produced?
P 18/ slides 20-24
-During starvation, glucose levels are falling. Glucose levels need to be maintained in order to
maintain brain activity.
- The alpha cells of the pancreas release glucagon. The adrenal medulla released epinephrine.
-Note: both act via a second messenger pathway.
-Also, there are no glucagon receptors outside of the liver.
-Glycogen is actively degraded in the liver.
-Once glucose-6 phosphate is generated, the liver will not use it.
-Gluconeogenesis occurs where non-carbohydrate precursors are converted into intermediates in
Note: The pentose phosphate pathway is a minor pathway that results in the generation of NADPH
for synthetic processes. Ribose-5 phosphate is also produced.
Describe and draw carbohydrate metabolism in red blood cells.
Since red blood cells lack mitochondria and cannot use amino acid
or fatty acid metabolism, they depend entirely on glycolysis.
p 19, slide 26
Describe and draw carbohydrate metabolism in brain tissue cells.
The brain has an absolute requirement for glucose. The adult
human brain consumes 120 grams of glucose/day. There is a very
small reserve of glycogen in brain tissue.
p 19, slide 27
Describe and draw carbohydrate metabolism in muscle and heart tissue cells.
Muscle and heart cells have major stores of glycogen. While the
liver has a larger amount of glycogen, muscles have a higher
concentration. Muscle cells cannot mobilize glycogen or glucose
p 19, slide 28