PRIN401 WEEK 7 BETA
fuel metabolism
fuel metabolism
can ethanol be used as a fuel
yes, ethanol can be oxidized to aceteldehyde. the acetylaldehyde is then oxidized to acetate and the acetate is converted to acetyl CoA.
hepatocytes can burn the acetyl CoA to make ATP (used as a fuel) or use it as a substrate to build fatty acids and/or ketones
OCT 16. METABOLISM II. DR. WARREN WILLIAMS
the profound effects ethanol has on metabolism are due to
the accumulation of acetaldehyde, acetyl CoA, NADH in the liver
what enzymes are used to degrade ethanol
alcohol dehydrogenase
it can also be oxidized to acetaldehyde by a hepatic "microsomal mixed function oxidase", which uses cytochrome P450.
_____________________________________________________
ethanol can compete for this enzyme and slow the rate at which some drugs are metabolized
In people with hypoglycemia, sugar (eg. dextrose) is always administered with thiamin because:
what chemical cuases the toxic effects of ethanol
acetaldehyde is toxic and can cause the systemic effects
with chronic alcoholism, how can an accumulation of fat in liver occur
2 factors contribute to this:
1)
beta oxidation of FA is slowed by high NADH/NAD+ ratio, XS FA are converted to TAGs
2)
the liver's ability to export lipids is reduced by alcohol, consequently TAG is stored, leading to a fatty liver.
what can a high NADH/NAD+ ratio in hepatocytes lead to
lactic acidosis + inhibits gluconeogenesis
_______________________________________________________
high NADH/NAD+ ratio promotes conversion of pyruvate to lactate --> lactic acidosis
also...
it can greatly decrease the hepatocyte's ability to use lactate as a substrate for gluconeogenesis
There are 2 main types of starvation: marasmus and kwashiorkor. Describe each.
marasmus is starvation as a result of lack of fuel, aka calorie deficiency
kwashiorkor is starvation due to protein deficiency in the diet, typically found in areas where people have very limited food variety, often eating mostly a single carbohydrate such as maize or rice.
(from `METABOLISM II` p.4)
RBCs rely on ________ and ____ ____ ____ (energy production mechanisms) for energy production
glycolysis and lactic acid fermentation
(since RBCs only use anaerobic mechanisms)
(from `METABOLISM II` p.1)
the glycogen supply in the body usually lasts __ day
one
(from `METABOLISM II` p5 )
As the fast continues beyond a day, the body shifts to depend more on ___ and less on ___ for fuel. The liver increases its rate of converting fatty acids to _____, and since this reduces the need for gluconeogenesis, the rate of ________ catabolism usually drops after a few days.
fat, protein
ketones
protein
(from `METABOLISM II` p.5)
what can ethanol promote, and under what conditions
it can promote hypoglycemia
under the following conditions:
malnourished (some alcoholics) -- low glycogen stores
children -- low glycogen stores
____________________________________________________
no recent dietary intake
alcohol will inhibit gluconeogenesis (ethanol does not inhibit glycogenolysis, so it tends to produce hypoglycemia only in people who have poor glycogen stores)
how is a fatty liver made
ethanol is catabolized, producing lots of NADH, which slows CAC.
buildup of acetyl CoA, which make fatty acids, which are stored in liver
+ if hypoglycemic, then increase in lipolysis and FA are taken up by fatty liver
how does disulfram work
it will inhibit aldehyde dehydrogenase.
with this drug, they are unable to metabolize the acetylaldehyde fast enough and it will accumulate.
the accumulation will cause nausea, vasodilation, etc and deter them from using alcohol
OCT 17. PHARMACOLOGY OF EICOSANOIDS. DR. STAN BARDAL. Explain how the synthesis of cholesterol can be inhibited by a drug.
It can be inhibited by HMG CoA reductase inhibitors (aka statins).
This is because HMG CoA reductase leads to synthesis of cholesterol.
(from "PHARMACOLOGY OF EICOSANOIDS p.2)
Describe how drugs that treat Alzheimer's and Parkinson's Disease work.
Drugs that treat Alzheimer's disease are usually Acetylcholinesterase inhibitors. Since Acetylcholine becomes depleted in Alzheimer's , Acetylcholinesterase inhibitors will prevent the breakdown of acetylcholine, thereby increasing acetylcholine levels .
Drugs that treat Parkinson's disease are usually Monoamine Oxidase (MAO) inhibitors. Since Dopamine becomes depleted inParkinson's, MAO inhibitors will prevent the breakdown of dopamine, thereby increasing dopamine levels.
(from "PHARMACOLOGY OF EICOSANOIDS p.2)
Eicosanoids are 20 carbon _____ , which is a substance that is rapidly synthesized, acts quickly and locally, and is repidly degraded. Eicosanoids are derived from ________ acid
autocoids
arachidonic
(from "PHARMACOLOGY OF EICOSANOIDS p.3)
What are the two fundamental pathways of interest for drug development in the arachidonic acid cascade? List all the products that each pathway produces.
The Arachidonic Acid cascade has 2 fundamental pathways :
- Lipoxygenase (LO) pathway --> produces Leukotrienes
- CycloOXygenase (COX) pathway --> produces Prostaglandins (PG), Thromboxane A2 (TxA2), and Prostacyclin (PGI2)
(from "PHARMACOLOGY OF EICOSANOIDS p.3)
ASA 's brand name is ___________, Ibuprofen's brand name is _________, and acetaminophen's brand name is _________. Which of these are NSAIDs?
ASA: ASpirin
Ibuprofen: Advil
Acetaminophen: Tylenol
ASA and Ibuprofen are NSAIDs.
(from "PHARMACOLOGY OF EICOSANOIDS p.4)
A non-selective COX inhibitor, such as ASA, would have ___________ effects while a COX-2 inhibitor would not.
ASA is an __________ inhibitor of COX enzymes.
antiplatelet
irreversible
(The irreversible inhibition makes ASA a more effective antiplatelet agent than reversible COX inhibitors.
(from "PHARMACOLOGY OF EICOSANOIDS p.6)
OCT14, 2014. ENDOCRINE REGULATION OF METABOLISM. Glucagon is released when blood _____ and _____ are low. What are the four effects of glucagon?
Glucagon is released when blood glucose and insulin are low.
The 4 effects are:
- increases gluconeogenesis
- increases glycogenolysis
- increases lipolysis of TAG
- decreases glycogen synthesis
from "ENDOCRINE REGULATION OF METABOLISM p.7"
Epinephrine is produced by cells of the _____ _____, and it is a derivative of ______. It acts on the ____, _____ tissue, and ________ _______. It is released when _____ _____ levels are low.
Epinephrine is produced by cells of the adrenal medulla, and it is a derivative of tyrosine. It acts on the liver , adipose tissue, and skeletal muscle. It is released when blood glucose levels are low.
from "ENDOCRINE REGULATION OF METABOLISM p.7"
What are the 5 effects of epinephrine?
- increases glycogenolysis
- increases gluconeogensis
- increases lipolysis
- increases glucagon secretion
- decreases insulin secretion
from "ENDOCRINE REGULATION OF METABOLISM p.7"
Cortisol has ________ effects, is is produced by the adrenal _________, and it is a derivative of ________. It is released during a __________ fast.
What are the 3 effects of cortisol?
Cortisol has Catabolic effects, is produced in the adenal Cortex, and is a derivative of Cholesterol
It is released during a prolonged fast.
- increases glucose production
- increases lipolysis
- decreases glucose utilization
from "ENDOCRINE REGULATION OF METABOLISM p.7-8"
Growth hormone is produced and secreted from ______ (type of cell) of the anterior pituitary. It is released during a _________ fast.
What are the 3 effects of GH?
Growth hormone is produced and secreted from somatotropes (type of cell) of the anterior pituitary. It is released during a prolonged fast.
- increases glucose production
- increases protein synthesis (growth)
- decreases glucose utilization (to save glucose for the brain)
from "ENDOCRINE REGULATION OF METABOLISM p.8"
list the sources of fuel during exercise
stored: ATP + creatine phosphate
carbohydrate
fat
protein
blood lactate
Give 4 examples of diabetic complications.
- diabetic retinopathy
- peripheral neuropathy
- kidney failure
- heart disease
from "ENDOCRINE REGULATION OF METABOLISM p.8"
Which of the following are similarities between cortisol and growth hormone? (p. 8 of Sep 25 notes)
in the breakdown of glucose, which segments are aerobic and which are anaerobic (ie; what is the point were it goes from aerobic to anaerobic)
from pyruvate to acetyl CoA
that turns from aerobic to anaerobic (the krebs cycle and beta oxidation is aerobic)
describe the pathophysiology of diabetic ketoacidosis in four steps .
1. absolute insulin deficiency causes the body to rely on alternative energy sources eg. gluconeogenesis from fats
2. increased lipolysis causes high free Fatty acids, which causes high conc. of ketone bodies
3. the result is ketoacidosis and hyperosmolarity (dehydration )
4. These could result in LOC (Loss Of Consciousness) and Death
from "ENDOCRINE REGULATION OF METABOLISM p.9"
when you first start excercising, what molecules are you going to use for energy
you will use ATP and creatine-phosphate
________________________________________________________
creatone-PO32 + ADP + H+ <--> ATP + creatine
Fat cells are endocrine cells. Fat cells produce and secrete ____, which signal the _______ (brain part) to decrease _____ _______ and increase _______ _________.
Fat cells are endocrine cells. Fat cells produce and secrete leptin, which signal the hypothalamus (brain part) to decrease food intake and increase energy expenditure.
from "ENDOCRINE REGULATION OF METABOLISM p.10"
(this is the last card for this lecture)
OCT 15, 2014. EXERCISE METABOLISM. DR. KATHY GAUL. (place the first question here)
(ANSWER)
in the hepatocyte:
glycogenolysis and gluconeogenesis create glucose, which is transported into the blood
in the adicocyte:
TAGs will be broken down and glycerol will go to the liver and FA go to blood stream
in skeletal muscles:
glucose is broken down into pyruvate, which is then broken down into lactate (exported into blood), and then transformed into acetyl-coA
when glucose is degraded to pyruvate, what happens
2 pyruvate molecules are made, and 2 ATP molecules are made
what happens when the exercise intensity increases
harder to get O2 to ETC
and
pyruvate will start to accumulate in the muscles, which turns into lactate in the muscles
epinephrine and glucagon in exercise metabolism: What are the similarities between the actions of epinephrine and glucagon?
from "EXERCISE METABOLISM p. 5"
what are the 3 main energy sources for muscle contraction
1) creatine phosphate reaction
2) glucose --> lactate reaction (anaerobic)
3) fatty acids (at rest: mostly fatty acids; moderate activit: fat + glucose)
What are the 2 ways we can trigger GLUT4 (glucose transporters) insertion into the plasma membrane for the facilitated diffusion of glucose into cells?
first way: as described in the diagram, insulin receptors are activated by insulin binding, the AMPK pathway is activated, thus resulting in visicles with GLUT4 transporters inserted into the sarcolemma
second way: Exercise can trigger insertion of GLUT4 into the sarcolemma independent of AMPK and insulin. It is important to know that this is how skeletal muscles continue to import glucose despite depressed insulin levels during exercise
* sarcolemma is the name of the cell membrane of a muscle cell
from "EXERCISE METABOLISM p. 6"
(this is the last flash card for this lecture)
briefly describe distinguishable features of muscles
morphological (small to big)
histochemical (oxidative to glycolytic)
functional (slow to fast)
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Flashcards
OCT14, 2014. ENDOCRINE REGULATION OF METABOLISM. Glucagon is released when blood _____ and _____ are low. What are the four effects of glucagon?
Glucagon is released when blood glucose and insulin are low.
The 4 effects are:
- increases gluconeogenesis
- increases glycogenolysis
- increases lipolysis of TAG
- decreases glycogen synthesis
from "ENDOCRINE REGULATION OF METABOLISM p.7"
Epinephrine is produced by cells of the _____ _____, and it is a derivative of ______. It acts on the ____, _____ tissue, and ________ _______. It is released when _____ _____ levels are low.
Epinephrine is produced by cells of the adrenal medulla, and it is a derivative of tyrosine. It acts on the liver , adipose tissue, and skeletal muscle. It is released when blood glucose levels are low.
from "ENDOCRINE REGULATION OF METABOLISM p.7"
What are the 5 effects of epinephrine?
- increases glycogenolysis
- increases gluconeogensis
- increases lipolysis
- increases glucagon secretion
- decreases insulin secretion
from "ENDOCRINE REGULATION OF METABOLISM p.7"
Cortisol has ________ effects, is is produced by the adrenal _________, and it is a derivative of ________. It is released during a __________ fast.
What are the 3 effects of cortisol?
Cortisol has Catabolic effects, is produced in the adenal Cortex, and is a derivative of Cholesterol
It is released during a prolonged fast.
- increases glucose production
- increases lipolysis
- decreases glucose utilization
from "ENDOCRINE REGULATION OF METABOLISM p.7-8"
Growth hormone is produced and secreted from ______ (type of cell) of the anterior pituitary. It is released during a _________ fast.
What are the 3 effects of GH?
Growth hormone is produced and secreted from somatotropes (type of cell) of the anterior pituitary. It is released during a prolonged fast.
- increases glucose production
- increases protein synthesis (growth)
- decreases glucose utilization (to save glucose for the brain)
from "ENDOCRINE REGULATION OF METABOLISM p.8"
list the sources of fuel during exercise
stored: ATP + creatine phosphate
carbohydrate
fat
protein
blood lactate
Give 4 examples of diabetic complications.
- diabetic retinopathy
- peripheral neuropathy
- kidney failure
- heart disease
from "ENDOCRINE REGULATION OF METABOLISM p.8"
Which of the following are similarities between cortisol and growth hormone? (p. 8 of Sep 25 notes)
in the breakdown of glucose, which segments are aerobic and which are anaerobic (ie; what is the point were it goes from aerobic to anaerobic)
from pyruvate to acetyl CoA
that turns from aerobic to anaerobic (the krebs cycle and beta oxidation is aerobic)
describe the pathophysiology of diabetic ketoacidosis in four steps .
1. absolute insulin deficiency causes the body to rely on alternative energy sources eg. gluconeogenesis from fats
2. increased lipolysis causes high free Fatty acids, which causes high conc. of ketone bodies
3. the result is ketoacidosis and hyperosmolarity (dehydration )
4. These could result in LOC (Loss Of Consciousness) and Death
from "ENDOCRINE REGULATION OF METABOLISM p.9"
when you first start excercising, what molecules are you going to use for energy
you will use ATP and creatine-phosphate
________________________________________________________
creatone-PO32 + ADP + H+ <--> ATP + creatine
Fat cells are endocrine cells. Fat cells produce and secrete ____, which signal the _______ (brain part) to decrease _____ _______ and increase _______ _________.
Fat cells are endocrine cells. Fat cells produce and secrete leptin, which signal the hypothalamus (brain part) to decrease food intake and increase energy expenditure.
from "ENDOCRINE REGULATION OF METABOLISM p.10"
(this is the last card for this lecture)
OCT 15, 2014. EXERCISE METABOLISM. DR. KATHY GAUL. (place the first question here)
(ANSWER)
in the hepatocyte:
glycogenolysis and gluconeogenesis create glucose, which is transported into the blood
in the adicocyte:
TAGs will be broken down and glycerol will go to the liver and FA go to blood stream
in skeletal muscles:
glucose is broken down into pyruvate, which is then broken down into lactate (exported into blood), and then transformed into acetyl-coA
when glucose is degraded to pyruvate, what happens
2 pyruvate molecules are made, and 2 ATP molecules are made
what happens when the exercise intensity increases
harder to get O2 to ETC
and
pyruvate will start to accumulate in the muscles, which turns into lactate in the muscles
epinephrine and glucagon in exercise metabolism: What are the similarities between the actions of epinephrine and glucagon?
from "EXERCISE METABOLISM p. 5"
what are the 3 main energy sources for muscle contraction
1) creatine phosphate reaction
2) glucose --> lactate reaction (anaerobic)
3) fatty acids (at rest: mostly fatty acids; moderate activit: fat + glucose)
What are the 2 ways we can trigger GLUT4 (glucose transporters) insertion into the plasma membrane for the facilitated diffusion of glucose into cells?
first way: as described in the diagram, insulin receptors are activated by insulin binding, the AMPK pathway is activated, thus resulting in visicles with GLUT4 transporters inserted into the sarcolemma
second way: Exercise can trigger insertion of GLUT4 into the sarcolemma independent of AMPK and insulin. It is important to know that this is how skeletal muscles continue to import glucose despite depressed insulin levels during exercise
* sarcolemma is the name of the cell membrane of a muscle cell
from "EXERCISE METABOLISM p. 6"
(this is the last flash card for this lecture)
briefly describe distinguishable features of muscles
morphological (small to big)
histochemical (oxidative to glycolytic)
functional (slow to fast)
describe type 1 muscles
discuss; stored fuel, oxidative phosphorlation, glycolytic, mitochondrial density, capillary density, resistance to fatigue, recruitment order
slow twitch
uses TAGs
high oxidative phosphorylation
low glycolytic
high mitochondrial density
high capillary density
high resistance to fatigue
*first recruited muscle type*
describe type IIa muscles
discuss; stored fuel, oxidative phosphorlation, glycolytic, mitochondrial density, capillary density, resistance to fatigue, recruitment order
glycogen, TAG
high oxidative metabolism
high glycolytic metabolism
high mitochondrial density
med. capillary density
med. resistance to fatigue
2nd recruitement order
describe type IIx/b muscles
discuss; stored fuel, oxidative phosphorlation, glycolytic, mitochondrial density, capillary density, resistance to fatigue, recruitment order
fuel source: ATP, CP
low oxidative phosphorylation
high glycolytic metabolism
low mitochondrial
low capillary density
int/low resistance to fatigue
3rd recruitment order
what are factors affecting fuel choice
intensity of exercise (demand and supply of ATP)
mobilization and oxidation rate of each fuel
availability of local intramuscular fuels
endocrine control
in addition to protecting the muscle glycogen, what will the body do
PROTECT BLOOD GLUCOSE
1. block entry of glucose into some tissues
2. mobilize glucose from liver
3. enhance gluconeogenesis in liver
4. mobilize FA from adipose tissues
what is the exercise fuel paradox
protect muscle glycogen (use something else)
but
protect blood glucose (maintain it)
what are the fuels used, and what is each one used for
glucose:
used for ATP synth
stored as glycogen or TAG
synthesized from precursors (glycerol, lactate, AA)
Fat:
used for ATP synth (oxidative phosphorylation)
stored as TAG
AA:
used for glucose production (gluconeogenesis)
used for synth of protein
what hormones are used for fuel metabolism
insulin
glucagon
epi/norepi
cortisol
GH
describe the 2 functional parts of the pancreas
exocrine: digestive enzymes released into intestine
endocrine: hormones secreted into blood
describe islets
they are clusters of cells in the pancreas
comprise 1~3% of the adult pancreas
the islet is made up of several cell types
where is insulin produced, and briefly describe the structure
produced by beta cells of the pancreatic islet
comprise 60-80% of islet
peptide hormone encoded by insulin gene
when is insulin secreted, and what will stimulate secretion
secreted in fed state
stimuli for secretion:
glucose
AA
FA
other hormones
which cells express insulin receptors
all cells have insulin receptors
insulin will regulate which cells metabolically?
liver
skeletal muscles
heart
adipose tissue
brain
pancreas
what happens to the body without insulin
cells cannot take up and utilize glucose
fuel metabolised is not stored
result:
XS nutrients circulate in the blood, but, cannot be used as a fuel source
what is the overall effect of insulin
the overall effect of insulin is to promote the utilization of glucose and the storage of surplus in the times of feast
insulin is an anabolic hormone
what tissues does insulin act on
liver
muscle
adipose tissue
generally speaking, what does insulin do
promote fuel storage:
inc. glycogen synth.
inc. glucose uptake/breakdown
inc. TAG synth and storage
inc. protein synth
inhibit fuel production
dec. gluconeogenesis
dec. glycogenolysis
dec. lipolysis
are lipids stored when there is low insulin
no
when does "starvation in the midst of plenty" occur
occurs when insulin is low
