Glyocgen Metabolism And Gluconeogenesis Flashcards
Roles of carbs in body
. Structural: proteoglycans important in CT
. Energy: source of ATP
. Storage of energy: glycogen storage in liver and muscle
. Cell-cell recognition: cell surface carbs
Monosaccharides
. Simple sugars (glucose and fructose) . Sweet . Glucose is from starches . Galactose is from milk . Fructose is from table sugar, fruit, honey
Disaccharide
. 2 monosaccharides joined together
. Lactose: composed of galactose and glucose (found in milk)
. Sucrose: glucose and fructose (common table sugar), major source of dietary fructose
Oligosaccharides
. Short chains of monosaccharides
Polysaccharides
. Long chains w/ no defined molecular weight
. No template used in synthesis
. Structural roles (ground substance, cellulose)
. Fuel storage: glycogen and plant starches form compact dense granules well-suited for cellular storage
Blood glucose level normal
5mM (100 mg/dL)
Hypoglycemia
. Blood glucose drops too low
Hypoglycemia adrenergic symptoms
. epinephrine release
. Occurs when glucose level falls off abruptly
. Anxiety, palpitation, tremor, sweating
Hypoglycemia neuroglycopenic symptoms
. From insufficiency delivery of glucose to brain
. Result of gradual decline in glucose (<40 mg/dL)
. Headache, confusion, slurred speech, seizures, coma, death
Hyperglycemia
. No symptoms
. If remains elevated diabetes mellitus may be the cause
Blood glucose maintained by ____
. Dietary intake of carbs: transport glucose from GI to blood
. Glycogen catabolism in liver: transport glucose from hepatocytes to blood
. Gluconeogenesis in liver: transport glucose from hepatocytes
Percentage glucose brain uses per day
25%
Why is glucose important for rbcs
Lack organelles, can’t make ATP other than glycolysis
When is glucose important for muscle cells?
. Prolonged and/or intense muscle activity
Role of mouth in dietary absorption of carbs
. Saliva contains alpha-amylase (ptyalin)
. Breaks bonds btw sugars in carbs
. Some glucose absorbed directly across mucous membrane
Role of stomach in dietary carb absorption
. Acidic environment (pH: 1-3)
. Inactivates alpha-amylase
. Acid cleaves bonds btw monosaccharide units of polysaccharides
Small intestine role in dietary carb absorption
. Neutral/slightly basic environment (pH: 6-8)
. Low pH from food triggers secretion of secretin
. Stimulates pancreas to secrete bicarbonate into small intestine to neutralize gastric acid and bring pH up
Pancreatic amylase
. Hydrolyzes starches and glycogen
Disaccharidases
. Sucrase: sucrose+H2O -> D-fructose and D-glucose
. Lactase: lactose+H2O -> D-galactose and D-glucose
. Resulting glucose foes to intensional cells, then blood, then tissues
. Galactose and fructose made are taken up in GI tract then moved to liver where they are converted into glucose by enzymes
Lack of dissaccharidase
. Diarrhea and gas when excess carbs consumed
. Water follows non-digested nutrients into GT causing diarrhea and gas is produced by bacteria in lower intestine that metabolize non-digested nutrients
. Relatively common in people
Large intestine role in dietary carb absorption
. escherichia coli: digest substances that we can’t digest making gas an end product
. Some nutrients absorbed (H2O, electrolytes, and anything left over)
. Carbs not digested are excreted (fiber)
Glycemic index
. Classifies food based on their ability to raise blood glucose after consumption
Goods with high glycemic index
. White bread
. Bagel
. White rise
Medium glycemic index foods
. Whole grain bread, oats, brown rice
Low glycemic index foods
. Lentils, fruits, non-starchy veggies
What lowers glycemic index of food?
Fat and fiber (putting butter on bread lowers glycemic index)
Why does glycemic index matter
. People w/ diabetes try to maintain blood glucose
. People w/ high GI diets have inc. risk of developing type 2 diabetes
Glycogen
. Readily accessible storage form of glucose
. Large branched polymer of alpha-D-glucose residues
. 90% of glucose molecules in glycogen are linear, 10% are branch points
. Makes glucose available btw meals
. Synthesis and degradation are different pathways regulated by hormones
Cellular location of glycogen
. Granules in the cytosol
Tissue location of glycogen
. Present in many by predominant in liver (10% weight is glycogen) for fuel reserve for blood and muscle (1-2% weight glycogen) for fuel reserve for own use
. More glycogen in muscle tissue than liver tissue because there is 2 fold more glycogen in total muscle than in liver
Glycogenin
. Protein at core of every glycogen molecule
. Has oligosaccharide chain of glucose from post-translational modification
. Auto-catalyzes addition of 8 more glucose resides onto chain
Glycogen synthase
. Takes over from glycogenin
. Using UDP-glucose as donor to add more glucose molecules one by one to the chain
What occurs in glycogen synthesis after glycogen synthase starts?
. Branching enzyme moves 5-8 glucose molecules from end and reattached it to interior site creating branch point
Why is glycogen branching important?
Creates large number of terminal glucose molecules
. Rate of synthesis/degradation can be faster
What enzyme is key step in glycogen synthesis?
Glycogen synthase
Glycogenolysis (glycogen breakdown)
. Glycogen phosphorylates uses inorganic phosphate to cleave individual glucose molecules from end of glycogen molecule making glucose-6P
. Continues cleaving until 4 glucose from branch point
. Transferase activity of bifunctional protein moves black of 3 glucoses from outer branch to another
. Debranching activity from Same protein uses H2O to cleave branch-point glucose
Glucose 6-phosphatase
. In liver but not muscle
. Cleaves phosphate from glucose-6P so liver generates glucose for body
Key regulated step in glycogenolysis
Glycogen phosphorylase
Glycogen metabolism regulation
. Substrate availability
. Allosteric regulation of key steps
. Hormones (tissue dependent) by altering covalent modification of key proteins
Why does liver has glucose 6-phosphatase and muscle doesn’t?
. Liver has to transport glucose from liver cells to blood stream for entire body
. Muscle only makes glucose for itself and it does not have to enter bloodstream
Glycogen phosphorylase inhibitors and activators
. Inhibitors: ATP, glucose-6P, glucose (liver)
. Activators: Ca and AMP in muscle
Glycogen synthase activators
Glucose-6P
Hormones involved in liver glycogen metabolism
. Insulin and glucagon
. Epinephrine
Hormones important in muscle glycogen metabolism
Insulin and epinephrine
What occurs to liver glycogen when epinephrine is present?
. Goes through G-protein Adenylate cyclase activation pathway to activate PKA
. PKA phosphorylates glycogen synthase to turn it odd
. Phosphorylates glycogen phosphorylase which activates it and glycogen is broken down
. Same thing occurs in muscle cells
What happens to liver glycogen when insulin is present?
. Insulin binds to RTK
. Protein phosphatase dephosphorylates glycogen synthase turning it on
. Glycogen phosphorylase is dephosphorylated and is turned off
. Glycogen is synthesized from glucose
Gluconeogenesis
. Pathway in cytosol in liver (and somewhat in cortex of kidney)
. non-carb precursors are used to synthesize glucose
How much glycogen in body is stored to last w/o gluconeogenesis?
1 day
Gluconeogenesis start and end products
2 pyruvate+4ATP+2GTP+2NADH+6H2O -> glucose+4ADP+2GDP+6P+2NAD+2H
Gluconeogensis enzyme for pyruvate to oxaloacetate and qualities
. Pyruvate carboxylase . Activated by acetyl CoA . Inhibited by ADP . Need biotin to function . Uses ATP and bicarbonate . Occurs in mitochondria . Replenishes oxaloacetate when TCA intermediates are drawn off for biosynthetic purposes
Gluconeogenesis enzyme from oxaloacetate to phosphoenol pyruvate
Phosphoenol pyruvate carboxykinase
. Inhibited by ADP
Number of pyruvate and oxaloacetate in gluconeogenesis
2 of each
Gluconeogenesis enzyme for fructose 1,6-BP to fructose-6P
Fructose 1,6-bisphosphatase
. Activated by citrate
. Inhibited by fructose 2,6-BP
Gluconeogenesis enzyme for glucose-6P to glucose and qualities
Glucose 6-phosphatase
. Important to enable liver to export glucose to blood
. Also found in glycogen catabolism in liver
Similarities btw glycolysis and gluconeogenesis
. Both primarily in cytosol
. Share enzymes
. Regulated allosterically and via hormones
Differences btw glycolysis and gluconeogenesis
. Glycolysis in all tissues, gluconeogenesis in liver and kidney
. Regulation is opposite
. Enzymes shared are used in opposite directions
Short term regulation of gluconeogenesis
. Opposite glycolysis
. Activities of enzymes controlled by availability of substrates
Long term regulation of gluconeogenesis
. Synthesis fo enzymes regulated by pattern of nutritional state
. Eating well inc. synthesis of liver glycolytic enzymes and dec. synthesis of gluconeogensis enzymes
. Starvation inc. liver gluconeogenesis enzymes and dec. glycolytic
Subcellular compartmentation w/ pyruvate carboxylase
. Oxaloacetate generated in mitochondria for gluconeogenesis is transported into cytoplasm via shuttle
When glucagon present in liver what occurs W/ gluconeogenesis?
. Gluconeogenesis stimulated
Cori cycle
. Lactate from muscle is carried into liver
. Converted to pyruvae via lactate dehydrogenase
. Pyruvate used in gluconeogenesis to make glucose
. Glucose brought back to muscle to start glycolysis
What does epinephrine stimulate in liver?
Gluconeogenesis
What occurs when glucagon present with liver glycogen?
Glycogen breakdown stimulated
Does not occur in muscle bc there are no glucagon receptors
Von Gierkes disease
Glucose 6-phosphatase deficiency
Causes hypoglycemia during fasting, hepatomegaly
