1
Q
what is it called when the body breaks down molecules to obtain energy and/or constituents for other pathways and what is it called when the bidt builds up larger molecules from samller components?
A
- break down = catabolism
- build up= anabolism
2
Q
low levels of ATP and high levels of ADP (or AMP) are indicators of?
A
- insufficient energy
3
Q
how does glucose provide energy?
A
- the 2 basic strategies that recur throughout various pathways are substrate-level phosphorylation and oxidative phosphorylation
4
Q
what is substrate-level phosphorylation?
A
- phosphate groups are shuffled around to create ATP
5
Q
what is oxidative phosphorylation (involving redox reactions)?
A
- the oxidation of a glycosidic/citric acid cycle intermediate is paired to the reduction of NAD+ to NADH or FAD to FADH2, which eventually contribute to oxidative phosphorylation
6
Q
what are the 2 basic ways that glucose can enter the bloodstream?
A
- absoprtion from the small intestine or from liver cells and cells in the renal cortex that produce glucose via gluconeogenesis or glycogenolysis
- they enter through the cells by glucose receptors
7
Q
what are the 4 GLUT transporters?
A
- GLUT1- expressed throughout the body, responsible for constant low-level baseling glucose intake. it is expressed more often in respnse to low blood sugar levels and less often in repsonse to high blood sugar levels and is especially common in fetal tissues and RBC. upregulated in many cancers
- GLUT2- expressed by liver cells, pancreatic beta cells and some kidney cells. BIDIRECTIONAL TRANSPORTER which is necessary in cells that carry out gluconeogenesis. pancreatic beta cells secrete insulin and this bidirectional transport pattern allows them to monitor blood glucose levels
- GLUT3- primarily expressed in neurons and placenta. it is a high-affinity transporter, meaning it will trasnport glucose effectively when blood glucose levels are low. this is one of the ways that the body can prioritize especially important areas even in times of deprivation or starvation
- GLUT4- expressed in non-smooth mucle and in adipose tissue. it is regulated by insulin and its basic job is to store glucose in skeletal muscle, cardiac muscle and adipose tissue when a surplus of glucose is present in the blood. insulin causes higher concentrations of GLUT4 receptors to be expressed in the p.m., thereby increasing glucose uptake into cells and reducing blood sugar levels
8
Q
what hormones can increase blood glucose levels?
A
- cortisol and epinepherine/norepinepherine
9
Q
which metabolic pathway is universal to all forms of cellular life?
A
- glycolysis which allows cells to obtain some energy from glucose regardless of whether oxygen is present
10
Q
where does glycoloysis take place?
A
- the cytosol of cells
11
Q
what is the net equation for glycolysis?
A
- Glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 pyruvate + 2 NADH + 2 ATP + 2 H2O
12
Q
what is the major outcome of glycolysis?
A
- glucose is broken up, producing 2 molecules of pyruvate, a 3 carbon alpha-keto acid that participates in multiple pathways in the body
- NAD+ gets converted to NADH (part of a redox reaction, so NADH must be converted back to NAD+ for the process to continue)
- AD+, Pi → ATP cycle is one of the basic ways that energy is cycled in the cell, and this process represented the direct energy payoff of glycolysis
13
Q
how many steps is glycolysis and what are the 2 phases?
A
- 10 steps
- the investment phase- 2 molecules of ATP are required. this investment is made in order to break up glucose into two 3-C molecules (step 1-5)
- the payoff phase- 4 molecules of ATP are generated through the conversion of these 3-C intermediates to pyruvate, resulting in a net yield of 2 ATP per glucose (step 6-10)
14
Q
what is step 1 of glycoloysis?
A
- glucose → glucose-6-phosphate
- this reaction is catalyzed by hexokinase and consumes 1 ATP.
- it traps G6P within the cell and places a strong -2 charge on the molecule, ensuring it cannot diffuse through the p.m.
- maintains the concentration of glucose low, so glucose can keep being transported into the cell
- the basic idea is to add a phosphate group to glucose to separate it out from the ramining glucose in the cell
15
Q
what is step 2 of glycolysis?
A
- G6P → fructose-6-phosphatw (F6P)
- this is an isomerization reaction catalyzed by glucose-6-phosphate isomerase
- it is easily reversible
16
Q
what is step 3 of glycolysis?
A
- F6P → frucotse 1,6-biphosphate (F1,6BP)
- catalyzed by phosphofructokinase-1 (PFK1)
- most significant step of glycoloysis because it is the committed step and must undergo glycolysis.
- it is the rate-limiting step
- 2 phsophate groups need to be added to the 6-C precursor
17
Q
what is step 4 of glycolysis?
A
- F1,6BP → glyceraldehyde 3-phosphate (GADP) abd dihidroxyacetone phosphate (DHAP)
- catalyzed by frucotse-bisphosphate aldolase
- where the cleavage of a 6-C carbohydrate to 3-C molecule happens
18
Q
what is step 6 of glycolysis?
A
- DHAP → GADP
- catalyzed by triosephosphate isomerase
- this step is to make sure that we have 2 identical 3-C compounds for the payoff phase
19
Q
what is step 6 of glycolysis?
A
- GADP → 1,3-bisphosphoglycerate (1,3BPG)
- catalyzed by glyceraldehyde phosphate dehydrogenase (GAPDH)
- it catalyzes the converstion of NAD+ to NADH and it loads up our carbon chain with another phosphate group (this time obtained from Pi)
20
Q
what is step 7 of glycolysis?
A
- 1,3BPG → 3-phosphoglycerate (3PG)
- catalyzed by phosphoglycerate kinase (PGK)
- a phosphate group is transferred from our 3-C skeleton onto a molecule of ADP to create a molecule of ATP. point where we start actively getting energy out of the process and is a regulaotry point in the pathway
21
Q
what is step 8 of glycolysis?
A
- 3PG → 2-phosphoglycerate (2PG)
- this step just rearranges the phosphate group and is catalyzed by phosphoglycerate mutase
22
Q
what is step 9 of glycolysis?
A
- 2PG → phosphoenolpyruvate (PEP)
- this step is catalyzed by enolase
- another rearrangement step
23
Q
what is step 10 of glycolysis?
A
- PEP → pyruvate
- catalyzed by ptruvate kinase (PH)
- phosphate group is transferred from our 3-C skeleton to an ADP molecule, forming ATP
- this is the second ATP forming step and can also be regulated
- pyruvate serves as the final electron acceptor
24
Q
summary of glycolysis
A
25
in the absence of oxygen, what prvides a way for NAD+ to be regenerated?
* fermentation
26
what is ethanol fermentation?
* used by yeast and consists of 2 steps
* pyruvate loses a carboxylic acid functional group becoming acetaldehyde (CH3CHO) and carbon dioxide. this step is catalyzed by pyruvate decarboxylase
* alcohol dehydrogenase turnes acetaldehyde into ethanol in a reaction coupled to the conversion of NADH to NAD+
27
what is alctic acid fermentation?
* one step process
* pyruvate is converted to lactate by lactate dehydrogenase in a reaction that is also used to convert NADH to NAD+
* lactic acid fermentation is carried out in muscle cells in humans, because muscle cells often use both aerobic and anaerobic respiration
28
what is gluconeogenesis?
* process to create glucose
* occurs primarily in the liver and to some extent in the adrenal cortex
* can be important to replenish the stores of glycogen in muscle cells after they have been depleted by intense activity
29
how does glycolysis and gluconeogenesis differ?
1. gluconeogenesis can be used tp produce glucose from a variety of substrates including fatty acids and certain amino acids
30
in the mitochondria, pyruvate carboxylase converts pyruvate to?
* oxaloacetate by adding a COO- group
* oxaloacetate is briefly converted to malate for transport out of the mitochondria, where it is converted immediately back to oxaloacetate. at this point in the cytosol, PEP carboxykinase converts oxaloacetate to PEP
31
once pyruvate is converted to PEP, gluconeogenesis follows the same stages of glycolysis, but in reverse, for several steps until?
* fructose 1,6-bisphosphate (F1,6BP)
* in gluconeogenesis, the enzyme fructose 1,6-bisphosphatase catalyzes the hydrolysis of the phosphate group on C1 of F1,6BP resulting in fructose 6-phosphate (F6P) which is isomerized to glucose-6-phosphate (G6P)
32
the conversion of G6P to glucose is the final step where gluconeogenesis bypasses glycolysis by?
* in gluconeogensis, glucose-6-phosphatase catalyzes a hydrolysis reactioon in which G6P yields glucose and Pi
33
how is glycogen built up and what is glycogen?
* gkycogenesis
* glycogen is a branched polymer of glucose that is used to store glucose, primarily in liver and muscle cells. each glycogen molecule is formed around a core formed by the protein glycogenin, which serves as the base for glycogen synthesis. glycogen is highly branched and within each branch, glucose molecules are linked together by alpha(1-4) linkages, while separate branches are formed by alpha(1-6) linkages
34
what is the starting point for glycogenesis?
* G6P which is turned into G1P by phosphoglucomutase (this step is essentially a way to mark that a glucose molecule is being shinted toward glycogen synthesis)
35
what is the second step of glycogenesis?
* G1P is converted to UDP-glucose (nucleotide dugar) and it donates glucose to a growing strand og glycogen via the action of glycogen synthase, which forms alpha(1→4) connections to existing glucose molecules. this means that glycogen synthase cannot create new branches.
36
how are new branches (alpha(1→6) linkages) created in glycogen?
* an enzyme known as glycogen-branching enzyme creates them
37
when a new glycogen moelcule is created, the core protein glycogenin also helps catalyze the buildup of the first 8 glucose molecules, after which?
* glycogen synthase can take over
38
what is glycogenolysis?
* the process of releasing glucose molecules from glycogen
39
the major steps in glycogenolysis are catalyzed by?
* glycogen phosphorylase
* in this reaction a substitution reaction takes place, in which a phosphate group is added to replace the alpha(1→4) linkage. this process is known as phosphoyolysis and results in G1P which is then converted into G6P by phosphoglucomutase, which is also part of the gluconeogenesis pathway so that pathway takes over from here
40
what enzyme only works on alpha(1→4) linkages and what other enzyme only works on alpha(1→6) linkages?
* 1 to 4 = glycogen phosphorylase and glycogen synthase
* 1 to 6 = glycogen debranching enzyme
41
what is the pentose phosphate pathway?
* not primarily about energy, the point of this pathway is to shunt glucose 6-phosphate away from the glycolysis/gluconeogenesis pathway and use it to do other structurally important things
* namely, the pentose phosphate pathway converts NADP+ into NADPH and converts gluvose 6-phosphate into ribose 5-phosphate
* NADPH has 2 main functions: serves as a reducing agent needed for the synthesis of lipids and nucleic acids, and it helps protect against damage from reactive oxygen synthesis by regenerating the antioxidant glutathione from its oxidized form
* ribose-5-phosphate is used in nucleotide synthesis
42
the pentose phosphate pathway is broken up into 2 stages:
* the oxidative phase and the non-oxidative phase
43
what happens during the oxidative phase?
* glucose 6-phosphate is first converted to 6-phosphoglucono-beta-lactone by glucose-6-phosphate dehydrogenase
* this step produces 1 NADPH and is the rate limiting step of the process
* the next step converts 6-phosphoglucono-beta-lactone into 6-phosphogluonate to form ribulose-5-phosphate and NADPH
* a carbon is lost as CO2.
* once ribulose-5-phosphate is generated, it can easily be converted into ribose-5-phosphate
The oxidative phase is notable for the following reasons: 1. the main products of the pentose phospphate pathway are generated in the oxidative phase and 2. a carbon is lost as CO2
44
what is the non-oxidative phase of the pentose phosphate pathway?
* allows cells that don;t specifically need ribose-5-phosphate to process it in a way that feeds back into the glycolysis pathway and allows the oxidative phase to continue. more specficially, it involves multiple steps, through which the carbon skeleton of ribose 5-phosphate is rearranged, resulting in a net conversion of six 5-C sugars (ribose 5-phosphate) to five 6-C sugars
* frucotse 6-phosphate can be easily converted back into glucose-6-phosphate, which can re-enter glycolysis; additionally, glyceraldehyde 3-phosphate, which is another product of the non-oxidative phase, can also be shunted back into glycolysis
45
summary of the pentose phosphate pathway?
46
how is glycolysis regulated?
* glycolysis is upregulated when the cell needs mroe ATP. this can be signaled by relatively high concentrations of AMP/ADP, as well as by an abundance of extra inorganic phosphate
* glycolysis is downregulated when the cell doesn't need more ATP. this is most directly signaled by a high level of ATP, but is also indirectly signaled by abundant levels of NADH and by high lecels of citrate
* glycolysis is also subject to negative regulation, in which certain oriducts inhibit previous steps. most notably, glucose 6-phosphate, the first product of glycolysis, inhibits hexokinase, which catalyzes the conversion of glucose 6-phosphate
47
how is gluconeogenesis regulated?
* upregulated when the body specifically needs more glucose and as an alternate pathway to handle surplus pyruvate/acetyl-CoA that builds up when downstream metabolic processes (in particualr, the citric acid cycle) are saturated
* gluconeogenesis and glycolysis are regulated in tandem in ways that respond to hormonal signlaing from outside the body (most notably insulin and glucagon)
* glycogen is how cells store excess glucose, so glycogen breakdown occurs when cells need more glucose for either gluconeogenesis or glycolysis, and glycogen synthesis is upregulated when the cell has a surplus of glucose
48
glycolysis has 3 main regulatory points:
* the firsts tep in which hexokinase catalyzes the conversion of glucose to glucose 6-phosphate. hexokinase is negatively regulated by its product, glucose 6-phosphate, in order to keep the process balanced.
* glucokinase has a lower affinity for glucose and is not inhibited by glucose 6-phosphate, meaning it can help liver and pancreatic cells respond specifically to the amount of glucose in the environment, rather than metabolizing glucose based on the intracellular need for ATP
* the second main regulatory point of glycolysis is its committed step in which phosphofructokinase-1 (PFK1) catalyzes the formation of fructose 1,6-bisphosphate from fructose 6-phosphate. PFK1 is downregulated by high levels of ATP and citrate, which signal the cell is already producing enough energy, and is upregulated by high levels of AMP/ADP, which signal that the cell needs more energy. PFK1 also participates in the interwoven regulation of glycolysis and gluconeogenesis via the related enzyme PFK2 and its effector fructose 2,6-bisphosphate
* the final step is the last main regulatory point in which phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase (PK). PK is allosterically inhibited by high levels of ATP, as well as abundant acetyl-CoA and the presence of high levels of long-chain fatty acids in the cell. all of these indicators that the cell has sufficient energy supplies and therefore doesn;t need to process more glucose into ATP
49
gluconeogenesis regulation steps:
* its first step can be regulated so the conversion of pyruvate to aceyl-CoA is downregulated, and the conversion of the excess pyruvate to PEP is favoured
* when fructose 1,6-bisphosphate is converted to fructose 6-phosphate, bypassing the rate-limiting step of glycolysis, inhibited by AMP
* 2,6-biphosphate favours glycolysis and lower levels favour gluconeogenesis
50
how is fructose 2,6-biphosphate is regulated?
* produced by an enzyme known as phosphofructokinase-2 and broken down by fructose 2,6-biphosphatase. a single bifunctional enzyme actually carries out the activity of both PFK2 and fructose 2,6-biphosphatase. through a series of intermediate steps, glucagon promotes the activity of fructose 2,6-biphosphatase and inihibits the activity of PFK2, thereby reducing the levels of fructose 2,6-biphosphate and promoting the gluconeogenesis. in contrast, insulin upregualtes PFK2 activity to stimulate glycolysis
51
how is glycogen regulated in liver and muscle cells?
* in liver cells, the glucose stored in glycogen is primarily mobilized for gluconeogenesis when blood goucose levels are low
* in muscle cells, the glucose stored in glycogen is fed into glycolysis to generate the energy needed to support intense muscle contraction.
* in both liver and muscle cells, however, glycogen phosphorylase (the enzyme responsible for breaking down glycogen) is regulated both hormonally and allosterically
52
epinepherine is the main horomone that regulates glycogen phosphorylase in?
* muscle cells; it induces a signaling cascade that activates glycogen phosphorylase and stimulates the release of glucose 1-phosphate, which is eventually shunted into the glycolytic pathway.
* in liver cells, glucagon is the main hormone that triggers glycogen phosphorylase. this is one mechanism through which glycogen breakdown is prevented when enough glucose is already available
53
how does the allosteric regulation of glycogen phosphorylase work?
* differs slightly in muscle and liver cells
* in muscle cells, Ca2+ upregulates glycogen phosphorylase, as does AMP, which is a sign of low energy. essentially both of these stimuli signal that the muscle needs more energy for contraction.
* in contrast, in liver cells, glucose allosterically inhibits glycogen phosphorylase. this is one mechanism through which glycogen breakdown is prevented when enough glucose is already available
54
insulin upregulates glycogen synthase through:
* it inactivates a protein known as glycogen synthase kinase 3. which inhibits glycogen synthesis
55
summary of what regulates what?
1. glycogen synthesis: favoured by excess glucose and insulin (glycogen)
2. glycogen breakdown: favoured if cell needs glucose (glycogen)
3. glycolysis: favoured by signals that the cell needs more energy (pyruvate)
4. gluconeogenesis: favoured by signals that the body needs more blood glucose or by excess acetyl-CoA (pyruvate)
5. pentose-5P pathway: favoured by NADP+ inhibited by NADPH
MCAT biochem
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