Integration Flashcards
Central themes of metabolism
- ATP is the universal energy carrier
- ATP is generated by the oxidation of metabolic fuels
- glucose
- Fatty acids
- Amino acids
- NADPH is the redox agent for reductive biosynthesis
- Biomolecules are constructed form a small set of building blocks
- Biosynthetic and degradation pathways are distinct
What are the major metabolic pathways
- Glycolysis
- Gluconeogenesis
- Glycogen metabolism
- Fatty acid metabolism
- Citric Acid cycle
- Oxidative phosphorylation
- Amino acid metabolism
Only the ____ can carry out all of the reactions of the major metabolic pathways
Liver
What are the key junction points of the 7 major metabolic pathways
- Glucose-6-phosphate
- Pyruvate
- Acetyl CoA
When glucose is transported into the cell it is rapidly phosphorylated to _______, which may be catabolized into______, stored as ______ or converted into _______ by the PPP
Glucose-6 phosphate, pyruvate, glycogen, ribose-5-Phosphate
Glucose 6-phosphate can be generated form _____ stores or by ______
glycogen or by gluconeogeneisis
Pyruvate is generated from glucose 6-phosphate by ______.
Glycolysis
Pyruvate is converted into lactate under _____ to regenerate _____
anaerobic conditions, to regenerate NAD+
Lactate must be subsequently oxidized back to _____
pyruvate
pyruvate can be transaminated to form
alanine
Pyruvate may be carboxylated to form ____ in the matrix of the mitochondria, this is the first step in ____
OAA, Gluconeogenesis
Pyruvate may be reduced into ____ by the pyruvate dehydrogenase complex
Acetyl CoA
Acetyl CoA is the activated 2-carbon unit produced by the _________ of pyruvate or by the ______ of fatty acids. it may also be produced by the degradation of ______
oxidative decarboxylation, beta-oxidation, ketogenic amino acids
Acetyl CoA may be completely oxidized into CO2 via the _____, converted into _____ which in turn may be converted into ketone bodies or cholesterol. Acetyl may be exported into the cytosol and converted into _____
TCA, HMG-CoA (3-hydroxy-3-Methyl-glutaryl CoA), fatty acids
major metabolic pathways that occur in the cytosol
- Glycolysis
- Pentose phosphate pathway
- Fatty acid synthesis
Major metabolic pathways that occur in the mitochondrial matrix
- Citric acid cycle
- Oxidative phosphorylation
- Beta-Oxidation of Fatty acids
- Keton-Body formation
major metabolic pathways that interplay of both cytosol and mitochondrial matrix
Gluconeogenesis and urea synthesis
____ is the primary fuel for the brain
Glucose
only under prolonged starvation does the brain use
ketone bodies as fuel
The brain has ___ capacity to store fuels and needs a continuous supply of glucose
no
The average brain consumes ____ g of glucose a day
120 grams
70% of the brains glucose intake is used to maintain
the Na+, K+ membrane potentials
Glucose is transported into the brain by the ______ glucose transporter
GLUT3
Fatty acids cannot be used as fuel for the brain because they
cannot cross the brain blood barrier
3 possible outcomes for glucose-6-phosphate
- Glycogen
- Pyruvate
- Ribose-5-P
4 possible outcomes of pyruvate
- Acetyl-CoA
- Lactate
- Alanine
- OAA
3 possible outcomes of acetyl-CoA
- CO2
- Fatty acids
- Ketone bodies
What is the number 1 metabolic player
Liver
functions of liver
- responds quickly to dietary conditions because of rapid turnover of its enzymes
- Processes most incoming nutrients
- Maintains constant concentrations of nutrients in blood (e.g. via gluconeogenesis), smoothing out fluctuations due to the starve-feed cycle
- processes toxins and wastes (e.g. through urea cycle)
- synthesizes and secretes plasma proteins
Liver primarily depends on _____ of _____ for its own energy needs
beta-oxidation of fatty acids
Amino acids go directly to the liver thought the _____ after absorption
portal vein
The liver uses amino acids to make _____, for _____, for biosynthesis of nitrogen-containing molecules, or ____
proteins, for gluconeogenesis, for biosynthesis of nitrogen-containing molecules, or for fuel
Adipose tissue is the metabolic _____
maintainer
adipose tissue stores TAGs and releases FAs and glycerol as signaled by _____/_____
glucagon/epinephrine
TAGs with c-AMP-activated and lipases —–>
fatty acids + glycerol
What is the turnover of TAGs a day
50-60 g/day
What is the long-term energy system
Oxidative system
What is the short term energy system
Anaerobic glycolysis
What is the immediate energy system
Phosphagen system
What is the reaction in the phosphagen system.
phosphocreatine + ADP ——> ATP + Creatine
Phosphocreatine lasts about
10 seconds
Explain the reactions under anaerobic conditions
ATP reserves are used in about 1 to 2 seconds
Phosphocreatine lasts about another 10 seconds
next 1 to 2 minutes is Glycogen–>G-6-P —-> Pyruvate —–> lactate
Fate of lactate
Cooperation between muscles and liver (Cori Cycle) to regenerate glucose from lactate
Can the heart burn lactate
Yes
Liver must use ____ in synthesis of glucose from lactate
ATP (think gluconeogenesis)
Does the brain have any significant energy reserves
No
The brain is dependent on blood glucose at ____ to maintain ion gradients
4.5mM
The Brain uses ____% of the total O2 consumed by a resting human
20%
After several _____ of low glucose, the brain switches to use of ______, which are degraded via TCA. Thus conserving the body’s _____
days, ketone bodies. Proteins
What is the normal range of blood glucose
90-60
Around a blood glucose of about ________ the pt will have subtle neurological signs; hunger release of glucagon, epinephrine, cortisol, sweating, trembling
40-55
Around a blood glucose of about _____ the pt will become lethargic, have convulsions, and possible coma
30-40
At blood glucose lower than _______ the pt will have permanent brain damage (if prolonged) and possible death
10-0
The mechanical power of the heart is fueled by ____ and _____
fats and carbohydrates (fatty acid oxidation and glycolysis)
does insulin inhibit gluconeogenesis
YES
Insulin deficiency or resistance can lead to
Hyperglycemia
Metabolic syndrome
Diabetes
Metabolic effects of insulin
Increase in glucose uptake (muscle, adipose)
increase in glucose uptake (liver)
Increase in glycogen synthesis (liver, muscle)
decrease in glycogen breakdown (liver, muscle)
increase in glycolysis, Acetyl-CoA production (liver, muscle)
Increase in fatty acid synthesis (Liver)
increase in TAG synthesis (adipose tissue)
Target enzymes that insulin induces
- Glucose transporter (GLUT4)
- Glucokinase
- Glycogen synthase
- PFK-1 (by increase in PFK-2)
- Pyruvate dehydrogenase complex
- Acetly-CoA carboxylase
- Lipoprotein lipase
Target enzymes that insulin inhibits
glycogen phosphorylase
What is the insulin receptor
Receptor Tyrosin Kinase (RTK)
Insulin binding to Receptor tyrosin kinase triggers
autophosphorylation at tyrosine
Metabolic effects of epinephrine
- increases glycogen breakdown (muscle, liver)
- decreases glycogen synthesis (muscle, liver)
- Increases gluconeogenesis (liver)
- Increases glycolysis (muscle)
- Increases fatty acid mobilization (adipose tissue)
- increases glucagon secretion
- Decreases insulin secretion
Epinephrine receptors act through ______
G proteins
Metabolic effects of glucagon
- increase glycogen breakdown (liver)
- Decrease in glycogen synthesis (Liver)
- Decrease in glycolysis (liver)
- Increase gluconeogenesis (liver)
- increase in fatty acid mobilization (adipose tissue)
- increase in ketogenesis
What is the major effect of glucagon
production and release of glucose by the liver
Glucagon inhibits what enzymes
- Glycogen synthase
- PFK-1
- Pyruvate Kinase
Glucagon induces what enzymes
- Glycogen phosphorylase
- FBPase-2
- PEP carboxykinase
- TAG lipase Perilipin phosphorylation
- Actyl-CoA carboxylase
Glucagon receptor acts through _______
G proteins
well feed muscle will
use glucose to make glycogen
fasting liver reactions
Acted on by Epinephrine and Glucagon
- Glycerol from adipose goes into gly-3P for gluconeogensis
- glycogenolysis
- Gluconeogenesis
- Fatty acid oxidation
- Ketone body synthesis
Fasting adipose reactions
-Acted on by glucagon and epinephrine
- TAG breakdown into FA and glycerol (FA will go to blood via albumin) (glycerol will go to liver)
- FA oxidation
- no glucose uptake
Fasting muscle reactions
acted on by epinephrine
- no uptake of glucose
- Glycogen breakdown
- FA oxidation form adipose
- Ketone body utilization (form the liver)
During an extended fasting state what changes from the early stages
Glycerol and FA are transported from the Adipose tissue to the liver. Glycogen reserves are gone so the liver resorts to making ketone bodies from FA. The muscle is stimulated by cortisol to breakdown proteins and send the amino acids to the liver. The liver uses the amino acids to produce react with pyruvate producing urea and glucose
Alcohol fatty liver disease
excess energy in NADH, fatty acid synthesis DHAP (glycerol) = increased TAGs
Energy is high when
High ATP, High NAD+, Low NADH
________ is the cellular energy sensor
AMP-Activated protein kinase (AMPK)
When ATP is low, AMPK is allosterically activated and
phosphorylates many targets controlling cellular energy production and consumption
The competition between ___ and ____ for binding to the AMPK allosteric sites determines the activity of AMPK
ATP and AMP
______ is released from fat and signals hypothalamus that you are full
leptin