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Starva on
Fasted state: too li le fuel,
glycogen breakdown
gluconeogenesis from amino acids
Ketone body synthesis
What factors contribute to Obesity
Appe te: lep n signaling pathway may be affec ve
Metabolism: ex) brown adipose ssue to burn excess fuel may be more plen ful in lean
individuals
Gene c Factors: could be mul ple muta ons
What is diabetes? What are the different types:
Defec ve regula on of lipid and carbohydrate metabolism
Type 1: Pancrea c B-cells can no longer produce insulin. Glucose cannot be taken up by the
cells, instead, high concentra on in blood and excreted in urine
Type 2: insulin resistance,
Hyperglycemia: high glucose in blood leads to protein modifica on, ssue damage; increased
risk of heart a ack, stroke and other circulatory problems.
Lipolysis: is s mulated in absence of insulin signaling leading to increased ketone body
synthesis.
What is a cancer cell and how is it made?
Cells with uncontrolled growth and requires lots of macromolecular synthesis, which requires
lots of precursors: amino acids, lipids, nucleo des. Lots of energy required.
What is the Warburg effect?
Cancer cells have a significant increase in the rate of glycolysis over oxida ve phosphoryla on
compared to normal healthy cells, EVEN IF there is sufficient O2. Most glucose is converted to
lactate.
, Generates less ATP, cell makes up for it by consuming more glucose.
What is the importance of glucose for prolifera ng cells?
Glucose is consumed to produce moderate levels of ATP,
Carbon is converted to metabolic pathways: amino acid, nucleo des, and fa y acids.
High ATP/AMP ra os are avoided in order to avoid inhibi on of rate limi ng steps in glycolysis
such as the phosphofructokinase reac on.
What is the importance if glutamate for prolifera ng cells?
Glutamate is consumed in large amounts in order to:
support amino acid synthesis
support nucleo de biosynthesis
Increases citric acid cycle intermediates for amino acid, nucleo de and fa y acid synthesis.
How do cancer cells reprogram their metabolism?
Pl3K/Akt ac va on s mulates glucose uptake and flux through early part of glycolysis.
Tyrosine kinase signaling nega vely regulates flux through late stages of glycolysis, making
glycoly c intermediates available for macromolecular synthesis as well as suppor ng NADPH
produc on
Myc drives glutamine metabolism, which also supports NADPH produc on.
LKB1/AMPK signaling and p53 decrease metabolic flux through glycolysis in response to cell
stress.
What are the components of Carbon Catabolism?
Catabolism: glycolysis, TCA cycle, ETS and oxida ve phosphoryla on, pentose phosphate
pathways; lipid and protein catabolism. Oxida on of high energy carbon compounds to CO2 and
H2O
Coupled to oxida ve phosphoryla on for ATP synthesis and NADPH produced.
What are the components of Carbon anabolism?
Synthesis of glucose, amino acids, fa y acids, nucleo des, etc.
Requires NAD(P)H, ATP and precursors from catabolic pathways.
What are the components of macromolecular synthesis?