Chapter 15 Flashcards
Cells & organisms maintain a ____________ steady state
Dynamic
Flux
Is the rate of one metabolite flow in metabolism
Flux through pathways must be regulated to do what?
- Achieve the physiological function of a tissue
- Maintain homeostasis
- Adapt too changing needs (such as development, nutrient intake, activity level, etc)
Flux depends on what?
- Amount of enzyme present
- The activity of the enzyme
Enzymes of _____________ steps are key regulatory enzymes that play a role in flux
irreversible
Both the amount & __________ activity of an enzyme can be regulated
Catalytic
The total activity of an enzyme can be changed by altering the number of its __________ in the cell or its effective activity in subcellular compartments or by modulating the activity of existing molecules
molecules
The different forms (isozymes) of hexokinase have different ____ values & are therefore affected differently by changes in glucose concentration
Km
Km = [S] that gives 1/2Vmax so if [S] increases then the reaction rate ________________ to help maintain homeostasis
Increase
ATP breaks down forming what?
ATP then AMP
When ATP is low AMP is ______ & vis versa
High
______ is used to regulate the body since small changes in its concentration results in a large relatvie change
AMP
______ isn’t used at all in body regulation since its in the middle & no relative change is shown
ADP
______ acts directly as an allosteric effector & also via phosphorylation of enzymes mostly by AMPK (AMP-activated protein kinase)
AMP
_______ is activated by elevated [AMP] or decreased [ATP] & when activated AMPK phosphorylates target proteins & shifts metabolism in a variety of tissues away from energy-consuming process
AMPK
Gluconeogenesis occurs mostly in the liver where its role is to regulate blood ______________
glucose levels
Isozymes
Are different proteins that catlayze the same reaction but have different genes
In muscle cells hexokinase I role is to convert glucose to glucose 6 phosphate at 0.1mM to provide _______ & when the concentration of glucose 6 phosphate is above that number, hexokinase I is temporarily inhibited to bring the concentration down
energy
In the liver hexokinase IV converts glucose to ________________ (& then to fructose 6 phosphate) when blood glucose is high (Like after a meal)
glucose 6 phosphate
The enzyme ______ has two binding sites (one where ATP binds & the other where AMPK binds) when [ATP] is high it signals that ATP is being produced faster than its being consumed so therefore ATP will inhibit PFK-1 by binding to an allosteric site which inhibits the binding for ATP as its substrate
PFK-1
________ (used for aerobic oxidation of pyruvate, etc) is also an allosteric regulator of PFK-1 so high [citrate] also inhibits ATP binding which further reduces the flow of glucose through glycolysis
Citrate
When [ATP] is _______& [AMP] is high it will bind to the allosteric subunit, therefore, releasing ATP in PFK-1 & stimulating the ATP binding site
low
The regulation of fructose 6 phosphates (for gluconeogenesis) or fructose 1,6 bisphosphate (for glycolysis) is regulated by ________ & ________ where high [ADP] & [AMP] stimulates glycolysis (high [ATP] & [Citrate] inhibits PFK-1 for glycolysis)
PFK-1 & FBPase-1
The 3 key enzymes for regulating glycolysis are what?
The enzymes at the3 irreversible steps
How does the liver regulate blood glucose?
With hexokinase IV & a regulatory protein, when [glucose] is high its insides the liver cytosol & when [Fructose 6 phosphate] is high its moved outside to the nucleus
The reaction of Fructose 6 phosphate to fructose 1,6 phosphate is inhibited by _________ & ________ & stimulated by AMP, ADP, & fructose 2,6 bisphosphate
ATP & Citrate
The regulation of glycolysis & gluconeogenesis is mediated (controlled) by _________________
Fructose 2, 6 bisphosphate
Glucose can be stored as __________
Glycogen
_________ is a branched polymer of alpha (1—>4) linked glucose with alpha (1—>6) linkage every 12 to 14 glucose units
Glycogen
Glycogen storage occurs mainly in the ___________ & Muscle
Liver
Glycogen is degraded to ____________ units for use in energy production
glucose
_____________ can be made from excess blood glucose or recycling of gluconeogenic metabolites like lactate or certain amino acids
Glycogen
Glycogenolysis (degradation)
The break down of glycogen to glucose 1-phosphate
Glycogenesis (synthesis)
The synthesis of glycogen
Glycogen breakdown is catalyze by the enzyme glycogen phosphorylase & in which an alpha 1-4 glycosidic linkage between two glucose residues at a ______________ end of glycogen undergoes attack by inorganic phosphate & removing the terminal glucose residue as alpha D-glucose 1 phosphate
Non-reducing end
_________________ (the end product of glycogen phosphorylase reaction) is converted to glucose 6 - phosphate by phosphoglucomutase (catalyzes a reversible reaction
Glucose 1 phosphate
Glycogen synthesis mostly occurs in _________ & skeletal muscles
Liver
The starting point of glycogen is _________________________ which is converted to glucose 1 - phosphate with the enzymes phosphoglucomutase where glucose 1phosphate is then converted into UDP-glucose by the enzymes UDP-glucose pyrophosphorylase
glucose 6 phosphate
The sugar nucleotide __________ donates glucose for glycogen synthesis
UDP- glucose
Sugar nucleotides
Compounds in which the anomeric carbon of sugar is activated by the attachment to a nucleotide through a phosphate ester linkage
Glycogen synthase can’t make the ______________ bonds found at the branch points of glycogen
alpha 1-6
____________________ is regulated by hormone-triggered covalent modification & allosteric effects
Glycogen phosphorylase
Glycogen phosphorylase is regulated in what 3 ways?
- Activated by phosphorylation
- Allosteric activation by AMP
- De-activation when glucose returns to normal (combination of allosteric effects & covalent modification)
What are the main hormonal signals?
- Insulin
- Glucagon
- epinephrine
Insulin _____________ glycogen degradation & increase synthesis in the liver
Decrease
Glucagon increases glycogen degradation & __________ glycogen synthesis in the liver
Decrease
epinephrine _____________ glycogen degradation & decrease glycogen synthesis in the liver & muscle
increase
The enzyme ______________ is responsible for activating phosphorylase by transferring a phosphoryl group to its Ser residue & is activated by epinephrine or glucagon (this is the activation of phosphorylation)
phosphorylase b kinase
______ the signal for muscle contraction binds to & activates phosphorylase b kinase promoting the conversion of phosphorylase b to active a form
Ca2+
When muscle returns to rest the enzyme ____________________ removes the phosphoryl groups form phosphorylase a converting it to the less active form b
phosphoprotein phosphate 1 (PP1)
Glycogen synthesis is also regulated by ______________________________
phosphorylation & dephosphorylation
Describe the regulation of muscle glycogen phosphorylase by covalent modification.
In the more active form of the enzyme, phosphorylase a, Ser14 residues. one on each subunit, are phosphorylated. Phosphorylase a is converted to the less active form, phosphorylase b, by enzymatic loss of these phosphoryl groups, catalyzed by phosphoprotein phosphatase 1 (PP1). Phosphorylase b can be reconverted (reactivated) to phosphorylase a by the action of phosphorylase b kinase. (See also Fig. 6-43 on glycogen phosphorylase regulation.)
Describe the effects of GSK3 on glycogen synthase activity.
Glycogen synthase a, the active form, has three Ser residues near its carboxyl terminus, which are phosphorylated by glycogen synthase Kinase 3 (GSK3). This converts glycogen synthase to the inactive (5) form. GSK3 action requires prior phosphorylation (priming) by casem Kinase (CKII). Insulin triggers activation of glycogen synthase b by blocking the activity of GSK3 (see the pathway for this action in Fig. 12-20) and activating phosphoprotein phosphatase 1 (PP1).
Describe glycogen phosphorylase of the liver as a glucose sensor.
Glucose binding to an allosteric site of the phosphorylase a isozyme of liver induces a conformational change that exposes its phosphorylated Ser residues to the action of phosphoprotein phosphatase 1 (PP1). This phosphatase converts phosphorylase a to phosphorylase b, sharply reducing the activity of phosphorylase and slowing glycogen breakdown in response to high blood glucose. Insulin also acts indirectly to stimulate PP1 and slow glycogen breakdown.
