Glucose Regulation and Formation Flashcards
what is metabolism?
- the enzyme catalyzed reactions that transform organic molecules in cells
- the sum of anabolism and catabolism
what is anabolism and catabolism?
- anabolism: synthesis of complex products; requires energy
- catabolism: degradation of complex precursors; yields energy
what are 3 important types of metabolism?
- carbohydrate metabolism
- lipid and fatty acid metabolism
- protein and amino acid metabolism
glucose oxidation via glycolysis yields what?
- pyruvate
- this is a source of ATP (energy)
glucose oxidation via pentose phosphate pathway yields what?
- ribose 5-phosphate (sugar that creates backbone for RNA, DNA, and NAD+
- this is an example of a molecular precursor
how is glucose used for energy storage?
-it is broken down into glycogen, starch, and sucrose
describe how glucose is a structural backbone
-it is used in the synthesis of structural polymers that function as components of the extracellular matrix and cell wall polysaccharides
name the 4 major pathways of carbohydrate metabolism
1) respiration
2) storage
3) regenerative
4) synthetic
what does the respiration pathway produce?
it forms ATP (from diet to ATP)
what does the storage pathway produce?
forms glycogen, glucose (glucose can be stored as glycogen)
what does the regenerative pathway produce?
forms glucose via gluconeogenesis
what does the synthetic pathway produce?
forms nucleic acids, lipids, amino acids (pyruvate used as backbone for amino acid formation)
glycolysis and gluconeogenesis, and glycogenesis and glycogenolysis are exclusive. what does this mean?
- they cannot occur at the same time within a particular cell
- so glycolysis and gluconeogenesis cannot occur at the same time, and glycogenesis and glycogenolysis cannot occur at the same time
why are some metabolic pathways exclusive?
-because they utilize many of the same enzymes, so movement can only occur in one direction (unidirectional)
which 4 pathways are catabolic? and what do they produce?
1) glycolysis –> ATP, NADH
2) citric acid cycle –> ATP, NADH
3) oxidative phosphorylation –> ATP, CO2
4) glycogenolysis –> glucose
what 2 pathways are anabolic? and what do they produce?
1) glycogenesis –> glycogen
2) gluconeogenesis –> glucose
the diet provides carbohydrates. name 4 enzymes used to digest complex sugars/digested into glucose
1) amylase
2) lactase
3) sucrase
4) maltase
after complex sugars from the diet are digested into glucose, where does the glucose go?
- it is transported into the blood
- energy source
- stored in liver or adipose tissue
what happens if you have too much glucose?
- the excess is converted into glycogen aka glucose homopolysaccharide
- glycogen is a set of long chains of glucose molecules put together at non-reducing ends
where is glycogen primarily found?
- liver (10% liver weight; hepatocytes)
- muscle (2% muscle weight; myocytes)
T or F: glycogen is necessary to maintain cellular osmolarity
true
free glucose molecules in cytoplasm would dramatically change osmolarity of cells, so conversion into glycogen reduces the demand of water that would otherwise be needed to maintain cellular osmolarity
what is the function of glycogenin?
- it is a molecule that induces the formation of glycogen chains
- it creates one branch, which has linkages to create secondary and tertiary tiers/branches, etc
where are glycogen chains stored?
granule organelles
what does glycogenesis do?
converts glucose to glycogen
what are the steps of glycogenesis, the enzymes used, and what does each enzyme do?
- hexokinase adds a phosphate to glucose
- phosphoglucomutase changes structure of glucose 6-phosphate (swaps P at 6’ carbon to the 1’ carbon)
- UDP-glucose purophosphorylase attaches glucose 1-phosphate onto UDP
- glycogen synthase
- glycogen branching enzyme adds a new glycogen branch to glycogen once every 4 residues
why is it important to put a phosphate onto glucose?
- phosphorylation of glucose prevents it from exiting the cell
- phosphate is energetically dense
what does glycogenolysis do?
creates glucose from glycogen
what are the steps in glycogenolysis, and what enzymes are involved?
what are the two fates of glucose created by glycogenolysis?
glucose 1-phosphate molecules are converted back to glucose 6-phosphate (via phosphoglucomutase) which can either 1) enter into glycolysis, or 2) be exported (only occurs in the liver) in cases where blood sugar is low
describe glucose export in the liver
- glucose 6-phosphate enters the endoplasmic reticulum via a G6P transporter
- glucose 6-phosphatase removes a phosphate, creating glucose
- glucose then leaves the ER via a glucose transporter
- glucose crosses leaves the cytosol and crosses the plasma membrane via a GLUT2 transporter
- enters the blood stream and increases blood glucose concentration
**alternatively, the glucose can be packaged into vesicles and excreted into golgi bodies
which 2 key enzymes regulate glycogen metabolism?
glycogen synthase and glycogen phosphorylase
what does glycogen synthase do?
- adds UDP-glucose to glycogen chain
- it is regulated by glycogen synthase kinase 3 which phosphorylates glycogen synthase, and is inactivated by phosphorylation
- glycogen synthase kinase 3 is inactivated by insulin
what does glycogen phosphorylase do?
- it regulates glycogenolysis by removing glucose 1-phosphate from glycogen
how does insulin signaling activate glycogenesis?
- insulin is released from pancreas in response to high blood sugar
- it activates GLUTs (glucose transporters), hexokinase, and glycogen synthase
- glycogen synthase then adds glucose to glycogen chains
epinephrine and glucagon activate what?
glycogenolysis
how do epinephrine and glucagon activate glycogenolysis? what are the 2 allosteric modulators involved?
- pancreas releases glucagon into liver in response to low blood sugar, epinephrine is also released into liver, which stimulates liver to break down glycogen via glycogenolysis, and glucose is released into blood stream
- epinephrine is released into musculature, stimulating muscle cell to undergo glycogenolysis and to increase the rate of glycolysis
- insulin and glucose are allosteric modulators
describe the two allosteric forms of glycogen pshophorylase
- phosphorylase b - less active
- phosphorylase a - active form
- allosterically regulated by insulin and glucose
- glucose can bind phosphorylase a, rendering it slightly less active
- insulin stimulates phosphorylase phosphatase 1 , which dephosphorylates phosphorylase a, resulting in the less active phosphorylase b
what does gluconeogenesis do?
- forms glucose from pyruvate or lactate
- it is the reverse of glycolysis
- predominantly occurs in the liver
what step/enzyme is the point of regulation in glycogenesis?
- uracil diphosphate-glucose to glycogen chain via glycogen synthase
- glycogen synthase dictates whether glycogenesis will occur or not
describe the steps in gluconeogenesis
- pyruvate –> oxaloacetate
- oxaloacetate –> phosphoenolpyruvate
- phosphoenolpyruvate –> 2-phosphoglycerate (2ATP in, 2ADP out)
- 2-phosphoglycerate –> 3-phosphoglycerate (2GTP in, 2GDP out)
- 3-phosphoglycerate –> 1,3-bisphosphoglycerate (2ATP in, 2ADP out)
- 1,3-bisphosphoglycerate –> glyceraldehyde 3-phosphate (2NADH + 2H+ in, 2NAD+ + 2P out)
- glyceraldehyde 3-phosphate –> dihydroxyacetone phosphate
- dihydroxyacetone phosphate –> fructose 1,6-bisphosphate
- fructose 1,6-bisphosphate –> fructose 6-phosphate
- fructose 6-phosphate –> glucose 6-phosphate
- glucose 6-phosphate –> glucose
what are the input costs of gluconeogenesis?
- 4 ATP
- 2 GTP
- 2 NADH + 2H+
- this all produces one molecule of glucose
describe the cori cycle
- occurs between the liver and musculature
- in muscle, ATP is produced by glycolysis for rapid contraction
- in the liver, ATP is used in syntehsis of glucose via gluconeogenesis during recovery
what is the point of regulation in gluconeogenesis?
- fructose 1,6-bisphosphate –> fructose 6-phosphate
- via fructose 1,6-bisphosphatase-1
- dictates whether glycolysis or gluconeogenesis occurs
what are the enzymes involved in each step of gluconeogenesis & glycolysis?
hint: all the same enzymes are used and create all the same products, just in reverse
where does gluconeogenesis occur? where within those cells is glucose 6-phosphate (last step before it turns into glucose)?
- gluconeogenesis occurs in hepatocytes in the liver
- glucose 6-phosphate is in the ER of hepatocytes
which 2 energy substrates regulate gluconeogenesis and glycolysis? describe how they do this
- phosphofructokinase and fructose 1,6-bisphosphatase
- in an energetically poor state (energy depletion), fructose 1,6-bisphosphatase becomes inactive and phosphofructokinase becomes active, stimulating glycolysis
- in high levels of energy (energy excess), phosphofructokinase becomes inactive and fructose 1,6-bisphosphatase becomes active, stimulating gluconeogenesis
what are some challenges with maintaining organism-wide metabolic homeostasis?
- cellular energetics change rapidly
- global metabolic demands change rapidly
- intracellular states drive physiologic changes that influence energetics
describe how intracellular states drive physiologic changes that influence energetics
- intracellular ATP/AMP content regulates metabolic function
- AMP Kinase (AMPK) detects intracellular AMP
- insulin/glucagon secretion influences metabolic function
what is the role of AMP kinase in “global” metabolic homeostasis?
- becomes activated as the concentration of AMP increases
- stimulates the brain to seek food/energy
- stimulates the heart to increase glucose uptake (aka rate of glycolysis) from vasculature
- inhibits fatty acid synthesis in adipose tissue and the liver
- inhibits insulin secretion from the pancreas (will instead start releasing glucagon)
- stimulates skeletal muscle to uptake fatty acids and glucose
describe the relative effects on the pancreas, liver, adipose tissue, and musculature of feeding vs fasting
feeding (insulin):
- panreas releases insulin
- liver: glycogen and FAs
- adipose: lipid storage, glycolysis, and lipid production
- muscle: glycolysis and glycogen production
fasting (glucagon):
- pancreas releases glucagon
- liver: gluconeogenesis, glycogenolysis, ketone and glucose release
- adipose: FA and glycerol release
- muscle: ketone metabolism, reduced glycolysis
what are the major fates of glucose?
- glycogen (energy storage)
- pyruvate (substrate for respiration)
- fatty acids
- amino acids (citric acid cycle)
- nucleic acids
