Download Biochemistry Full Course Study Notes and more Study notes Biochemistry in PDF only on Docsity!
Study Guide
Exam 1 Questions:
“Structure implies function” is a basic tenet of biochemistry, and it will never be the answer to any exam questions.However, this exam question asks you to explain this tenet. What does “structure implies function” mean? What are the implications of this statement in different organisms? Does the converse of the statement “function implies structure” hold true? Explain why or why not.
Answer:
The statement “structure implies function” means structure is important and specific to its function.For example, proteins are basically the drive in our bodily functions they are involved in different functions like enzymatic reactions or transportation.Every amino acid sequence is unique in order to make proteins that perform different functions. Also one protein structure in a human may be slightly different in another organism because of the different environments they are in. With that being said, I would say the statement “function implies structure” is not correct.We may find that two different species have a protein that carries the same function but could have a slightly different structure and that’s because these two species are different in the way they carry out their bodily functions so therefore different environments / nutritions would explain why the structures might not be the same.
Hydrogen bonds don’t contribute to the stability of two DNA strands hybridizing, yet they contribute to the stability of the duplex structure. Explain the differences between these two states, and why hydrogen bonds only stabilize one state. If a duplex DNA strand is denatured, do hydrogen bonds continue to stabilize the duplex? Explain your answer.
Answer:
The stability of the DNA double helix depends on a fine balance of interactions including hydrogen bonds between bases, hydrogen bonds between bases and surrounding water molecules, and base-stacking interactions between adjacent bases. Hydrogen bonds
are responsible for specific base-pair formation in the DNA double helix and a major factor to the stability of the DNA double helix structure.
The pentapeptide YGGFL will exhibit different chemical properties than the peptide LFGGY even though the amino acid sequences are “flipped” related to each other. Explain the difference in properties and justify your answer using biochemical knowledge. How is this different from duplex DNA with “flipped” nucleotide sequences? Would duplex DNA exhibit the same differences in properties? Why or why not?
Answer:
The reason why a “flipped” amino acid sequence would exhibit different chemical properties is because amino acid sequencing is very specific, the way you join amino aicds together will show different functions
YGGFL→ Try-Gly-Gly
LFGGY→ Leucine
You can see that the amino acid sequences start with a different amino acid and thats important
Polypeptides are read from left to right and the structure always includes an amine group at the left and a carbonyl group on the right
A duplex DNA with flipped nucleotide sequences would also exhibit different chemical properties as the flipped sequence would provide a different genome sequence as well changing the polarity as DNA has an antiparallel polarity with the 5 prime end and 3 prime end. the polarity (direction) is defined by the carbon atom in the sugar backbone of each strand and is described as 5′ to 3′ (said as 5 prime to 3 prime).
How do the steric conflicts within amino acid structures lead to the existence of regular secondary structures? What if these steric conflicts didn’t exist? Are there examples of the absence or reduction of steric conflict? What new structures are possible from the absence/reduction of steric conflict between amino acids?
Answer:
Steric hindrance creates a conflict within amino acid structures. In a cis structure, we could see steric hindrance while most structures want to be in a trans state because it is more stable in this conformation, there would be no interference. cis isomers have a 90o bond angle whereas trans
associations between molecules, providing the necessary shape and structure of DNA and proteins to function in the body.
Nucleic acid solution is always surrounded by salt ions. Explain this situation, why it occurs, and the consequences for double stranded nucleic acid if this situation is altered.
Answer
The reason why it occurs is because DNA is always found in a salty environment due to the the fact that the phosphate groups is negative so the salt cancels it out, making DNA neutral. Double stranded nucleic acids will push out all the water due to hydrophobic qualities so you find no water or fluid between because its a very compact structure.
Water is a ubiquitous element in almost every biochemical system and organism. Explain the biochemical role of water in any two processes.
Answer
Water's extensive capability to dissolve a variety of molecules has earned it the designation of “universal solvent,” and it is this ability that makes water such an invaluable life-sustaining force. On a biological level, water's role as a solvent helps cells transport and use substances like oxygen or nutrients. Water is an ideal medium for chemical reactions as it can store a large amount of heat, is electrically neutral, and has a pH of 7.0, meaning it is not acidic or basic. Additionally, water is involved in many enzymatic reactions as an agent to break bonds or, by its removal from a molecule, to form bonds. Because of its polarity and ability to form hydrogen bonds , water makes an excellent solvent, meaning that it can dissolve many different kinds of molecules.
Direct interspecies transmission of prion diseases is thought to be a slower and much more inefficient process than transmission within species, although it can clearly occur.Provide an example where interspecies transmission hasoccurredd and discuss why interspecies transmission is expected to be a particularly slow process. Is intraspecies transmission faster? Explain your answer.
Answer
A great example of how interspecies transmission occurs and how long it takes is mad cow disease. The prion disease started first in sheep then many years occurred and it made it in the
food of cows. The cow becomes sick after 10 years or so but it was already in our meat factories which led to humans consuming the meat. Humans become sick after 10 years or so after their consumption. This series of events show you that these prion diseases can take years and years to develop and that its a slow process.Humans who eat beef during this time wouldn’t have seen the effects after 10 years or so meaning in different species, the transmission of prion disease is very slow. I would say intraspecies transmission is faster since they have similar bodily functions compared to different species that may handle these functions in a different manner.
Protein folding is known to be a highly cooperative process. What does this mean, and based on your knowledge of protein structure, what does it imply?
Answer
The folding and unfolding of proteins is cooperative in nature. Under denaturing conditions such as high temperature part of the protein becomes unstable. The unstable segment because it interacts with the other part of the protein via non covalent interactions, begins to destabilize the other segments until the protein is completely denatured. This is to say that each segment of the protein works/cooperate with one another to unfold the protein. The reverse folding process in each state or along the pathway consists of energy specific intermediate states.Unfolded or misfolded proteins contribute to the pathology of many diseases.
Regular secondary structures are well-known, and are frequently found in molecular structures. Explain how these regular structures nevertheless lead to the vast number of different molecules and tertiary structures. Are irregular secondary structures necessary for the vast number of different molecules and tertiary structures? Explain your answer.
Answer
How do we recognize a protein that we are studying? Provide two different examples of the process and discuss their uses/flaws.
Answer
Metastable protein folding has been implicated in various disease. Explain the molecular process by which misfolded metastable proteins cause disease.
Answer
Substrate discrimination is a necessary component of enzyme specificity. How are different substrates discriminated between by an enzyme? Provide an example of an enzyme’s substrate specificity mechanism.
Answer:
The specificity of an enzyme is due to the precise interaction of the substrate with the enzyme. This precision is a result of the intricate three-dimensional structure of the enzyme protein.Substrates bind to a specific region of the enzyme called the active site. Most enzymes are highly selective in the substrates that they bind. Indeed, the catalytic specificity of enzymes depends in part on the specificity of binding.The specificity of binding depends on the precisely defined arrangement of atoms in an active site. Because the enzyme and the substrate interact by means of short-range forces that require close contact, a substrate must have a matching shape to fit into the site.the substrate may bind to only certain conformations of the enzyme, in what is called conformational selection. Thus, the mechanism of catalysis is dynamic, involving structural changes with multiple intermediates of both reactants and the enzyme.
How does the buffer environment affect an enzyme’s catalytic mechanism? Describe the molecular details of an example.
Answer:
The buffering compound prevents a severe pH-change and therefore a possible denaturation of the enzyme .PH not only affects the activity of the enzyme, but also affects the charge and shape of the substrate, so that the substrate cannot bind to the active site, or cannot be catalyzed to form a product. In a narrow range of pH, the structural and morphological changes of enzymes and substrates may be reversible.
Allostery is a regulatory mechanism controlling enzyme activity. How does the structure of the enzyme permit allosteric regulation in single enzymes, and in multi-protein complexes? Discuss an example.
Answer:
Allosteric enzymes consist of multiple subunits and multiple active sites. In allosteric enzymes, the binding of substrate to one active site can alter the properties of the other active sites on the same enzyme. A possible outcome of this interaction between subunits is that the binding of substrate becomes cooperative; the binding of substrate to one active site facilitates the binding
of substrate to the other active sites. In addition, the activity of an allosteric enzyme may be altered by regulatory molecules that reversibly bind to specific sites other than the catalytic sites.The catalytic properties of allosteric enzymes can thus be adjusted to meet the immediate needs of a cell. Allosteric enzymes are distinguished by their response to changes in substrate concentration in addition to their susceptibility to regulation by other molecules. Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway; ATCase is inhibited by CTP, the final product of the ATCase- initiated pathway.
Many isolated enzymes, if incubated at 37 C will be denatured. However, if the enzyme are incubated at 37 C in the presence of a substrate, the enzymes are catalytically active. Explain this phenomenon, including both the denatured and catalytically active states.
Answer:
As with many chemical reactions, the rate of an enzyme-catalysed reaction increases as the temperature increases. However, at high temperatures the rate decreases again because the enzyme becomes denatured and can no longer function.The optimum temperature in most enzymes is around 37 degrees Celsius. When the temperature increases, however, the enzymatic activity decreases. This is because higher temperatures tend to denature proteins, which in turn causes them to lose their functionality.Enzyme catalysis is detected by measuring either the appearance of product or disappearance of reactants.
Many enzymes are synthesized as an inactive precursor form, and then acquire a cofactor for activity. Explain this need of a cofactor, and provide an example.
Answer:
The catalytic activity of many enzymes depends on the presence of small molecules termed cofactors such as vitamins, minerals, and ATP .Cofactors are able to execute chemical reactions that cannot be performed by the standard set of twenty amino acids. An enzyme without its cofactor is referred to as an apoenzyme; the complete, catalytically active enzyme is called a holoenzyme.Cofactors are key components of enzyme pathways that facilitate the activity or regulation of enzymes. Cofactors can be metals or small organic molecules, and their primary function is to assist in enzyme activity. They are able to assist in performing certain, necessary, reactions the enzyme cannot perform alone. They are divided into coenzymes and prosthetic groups.
explained by the formation of a covalently bound enzyme–substrate intermediate. First, the acyl group of the substrate becomes covalently attached to the enzyme as p- nitrophenolate (or an amine if the substrate is an amide rather than an ester) is released. The enzyme–acyl group complex is called the acyl- enzyme intermediate. Second, the acyl-enzyme intermediate is hydrolyzed to release the carboxylic acid component of the substrate and regenerate the free enzyme. Thus, one molecule of p-nitrophenolate is produced rapidly from each enzyme molecule as the acyl-enzyme intermediate is formed. However, it takes longer for the enzyme to be “reset” by the hydrolysis of the acyl-enzyme intermediate, and both phases are required for enzyme turnover.
Enzyme inhibitors are pharmaceutically important. Discuss examples of the use of enzyme inhibitors as pharmaceuticals, including both the compound and the target enzymes.
Answer:
Enzyme inhibitor as pharmaceutical include the drug Omeprazole which used to inhibit the K+/H+ ATPase which is the enzyme that acidifies the stomach. If enzyme is too active will result in gastroesophageal reflux disease (GERD) or heartburn where stomach acid leaks back to esophagus and if may lead to esophageal cancer if untreated. Penicillin acts by covalently modifying the enzyme transpeptidase , thereby preventing the synthesis of bacterial cell walls and thus killing the bacteria. Aspirin acts by covalently modifying the enzyme cyclooxygenase , reducing the synthesis of signaling molecules in inflammation. captopril, protease inhibitor used to regulate blood pressure, is one of many inhibitors of the angiotensin-converting enzyme (ACE) , a metalloprotease. Indinavir (Crixivan), retrovir, and a number of other compounds used in the treatment of AIDS are inhibitors of HIV protease.
Describe situations in which isozymes are utilized to regulate enzyme activity and explain the types of differences encoded by the isozymes.
Answer:
Isozymes , or isoenzymes, are enzymes that differ in amino acid sequence yet catalyze the same reaction.They respond to different regulatory molecules. They are encoded by different genes , which usually arise through gene duplication and divergence. Isozymes can often be distinguished from one another by physical properties such as electrophoretic mobility. The existence of isozymes permits the fine-tuning of metabolism to meet the needs of a given tissue or developmental stage. Consider the example of lactate dehydrogenase (LDH), an enzyme that
catalyzes a step in anaerobic glucose metabolism and glucose synthesis. Human beings have two isozymic polypeptide chains for this enzyme: the H isozyme is highly expressed in heart muscle and the M isozyme is expressed in skeletal muscle.
Many damaging mutations in human affect collagen, resulting in diseases such as osteogenesis imperfecta and Ehlers-Danlos syndrome. While some of these mutations directly alter collagen genes (such as mutating the glycine in a Gly-X-Y repeat), other mutations affect the genes for other enzymes. Why do mutations in these other enzymes affect collagen and what specific molecular defects do they cause?
Answer:
Phosphoneacetyl-L-aspartate (PALA) is both a substrate analog and a potent inhibitor of asparate transcarbamylase because it mimics the two physiological substrates. However, in the presence of substrates, low concentrations of the unreactive PALA increase the reaction velocity. The maximal velocity is 17-fold greater than in the absence of PALA. Explain this velocity increase by low concentrations of PALA.
Answer:
Provide an example of proteolytic activation of an enzyme. As part of your answer, please explain the physiological importance of using proteolytic activation to acuvale this enzyme (as opposed to using other regulatory strategies such as allostery or isozymes) in addition to the normal expected biochemical information.
Answer:
Exam 3 Questions:
Describe 3 different roles of carbohydrates in the cell. Include illustrative examples for each role as part of your answer. Note that difference has to be a completely different function; differences based on the identity of the molecule will be considered to be the same role.
Answer:
Carbohydrates are important fuels and structural components. Carbohydrates attachment to a protein is the most common post-translational modification of proteins. The extracellular matrix
Answer:
G- proteins are guanine nucleotide binding proteins. These are GTPase switch proteins which get turned on when bound to ATP and off when bound to GDP. They are attached on the cytoplasmic side of the plasma membrane. Trimeric G proteins have three subunits called alpha beta and gamma subunits. Beta and gamma re always found together and the alpha subunit is always bounded with GDP when no ligand is attached to the receptor. When a ligand is present on a receptor the bounded GDP on the alpha subunit alternates with GTP. Ligand will bind with the GPCR receptor, this leads to the dissociation of GDP from the alpha subunit of the g protein and binds GTP to it. The binding of GTP with the alpha subunit dissociates the GTP alpha subunit from the G beta gamma complex. GTP alpha subunit and G-beta gamma complex then interacts with their respective effector protein. The G-protein will return to its original state after a time period the intrinsic GTPase activity of the alpha subunit of G proteins inactivates G alpha GTP by catalyzing the GTP hydrolysis. Then, G-alpha-GDP dissociates from its effector protein and again reassociates with G-beta-gamma subunit and terminates the signal transduction pathway.
How do phosphorylation cascades work in non-GPCR hormonal receptors to signal ligand binding? Discuss the molecular events in one example.
Answer:
The phosphorylation cascade acts as a signal transduction route, meaning that it conveys the signal of ligand binding to the cell and begins the process of the cell responding to the signal. This route is a major component of the communication that occurs between non-GPCR hormonal receptors, and it is necessary for the control of a large number of cellular functions. The insulin receptor signaling pathway is an example of a phosphorylation cascade that is involved in the signaling of a hormone receptor that is not a GPCR. During this stage of the process, insulin binds to the insulin receptor, which in turn activates a chain of protein kinases. After then, the active protein kinases phosphorylate downstream proteins in a certain order. Some examples of these proteins include the IRS proteins, PI3K, Akt, mTOR, and PKB/Akt. These proteins, in turn, activate additional proteins as well as transcription factors, which start the process of the cell responding to insulin binding. The final outcome is the activation of the metabolic pathways inside the cell, which ultimately results in the absorption of glucose as well as other nutrients.
Glycolysis utilizes substrate-level phosphorylation to generate ATP. Since the glycolytic pathway can generate ATP anaerobically, what molecular events enable humans to maintain glycolysis during anaerobic respiration? How are these events linked to the glycolytic pathway? Be biochemically specific in your answer.
Answer:
Glycolysis is the sequence of reactions that metabolize one molecule of glucose into two molecules of pyruvate with the concomitant net production of two molecules of ATP during anaerobic respiration. This process is anaerobic therefore it does not require oxygen because it evolved before substantial amounts of oxygen were accumulated in the atmosphere. Pyruvate can be further processed anaerobically to lactate or ethanol. As lactate dehydrogenase reoxidizes NADH to NAD+, the pyruvate is degraded to lactate. It is linked to the glycolytic process because it involved a series of enzymatic processes that convert glucose into pyruvate and energy sources such as NAD and ATP.
Reciprocal regulation is a key regulatory strategy used in various pathways. Describe the molecular principles governing this regulatory strategy in glycolysis/gluconeogenesis.
Answer:
Glycolysis and gluconeogenesis are regulated in a reciprocal fashion meaning when one process is highly active the other is inhibited. The whole purpose of the reciprocal regulation is that whe energy Is needed or glycolytic intermediate is needed for biosynthesis, glycolysis will predominate. When there is a surplus of energy and glucose precursors, gluconeogenesis will take over. Each process is regulated by phosphorylation/dephosphorylation and by the binding of other molecules. The charge of the cell (AEC- Adenylate energy charge) depends on the ATP and AMP levels of the cell. The concentration of ATP and AMP regulates the glycolysis and gluconeogenesis pathway. For example, if the cell has low energy, then it indicates that AMP levels in that cell are high. The AMP allosterically inhibits fructose 1,6 bisphosphatase and phosphofructokinase, thus promoting the glycolytic cycle and suppressing gluconeogenesis. When the blood glucose drops, the cell does gluconeogenesis and when the blood glucose is high (after a meal) cell promotes glycolysis.
enzyme pyruvate. In the cytosol, oxaloacetate is decarboxylated and rearranged to form phosphoenolpyruvate (PEP) via the enzyme PEP carboxykinase.3.Fructose 6-phosphate converts to glucose 6-phosphate via phosphohexose isomerase.
Describe the role of SH2 and SH3 protein domains in signal transduction. How do these proteins enable cascades?
Answer:
SH2 and SH3 domains are small protein modules that mediate protein-protein interactions in signal transduction pathways that are activated by protein tyrosine kinases. SH2 domains bind to short phosphotyrosine-containing sequences in growth factor receptors and other phosphoproteins. The SH3 domain of Src-family PTKs, which regulate many cellular functions, such as cell proliferation and differentiation, survival, migration and cytoskeletal modifications, is mainly involved in substrate recognition and downregulation of the kinase activity. Kinase cascades are a sequence of such cycles, in which the activated protein in one tier promotes the activation of the protein in the next one. The advantages of these cascades in signal transduction are multiple and the conservation of their basic structure throughout evolution suggests their usefulness.
How can glucose be synthesized from non-carbohydrate precursors? What precursors are utilized, and where to these precursors come from?
Answer:
In humans, gluconeogenic substrates can come from non-carbohydrate sources that can be converted to pyruvate or glycolytic intermediates (see figure). For protein breakdown, these substrates contain glycogenic amino acids (but not ketogenic amino acids). glycerol, from the breakdown of lipids containing odd-chain fatty acids (such as triglycerides) (but not straight- chain fatty acids, see below); from other parts of metabolism, including lactic acid from the Coli cycle. During prolonged fasting, acetone derived from ketone bodies also acts as a substrate, providing a pathway from fatty acids to glucose. Contribution increases with diabetes and prolonged fasting. The gluconeogenic pathway is highly endergonic until coupled with the hydrolysis of ATP or GTP, effectively rendering the process exergonic. For example, the pathway from pyruvate to glucose-6-phosphate requires 4 molecules of ATP and 2 molecules of GTP to proceed spontaneously. These ATPs are provided from fatty acid catabolism via beta- oxidation.
In mammals, gluconeogenesis has been thought to be restricted to the liver, kidney, intestine, and muscle, but recent evidence suggests that gluconeogenesis occurs in brain astrocytes. organs use slightly different gluconeogenic precursors. The liver preferentially uses lactate, glycerol, and glycogenic amino acids (particularly alanine), while the kidneys preferentially use lactate, glutamine, and glycerol. Lactate from the coli cycle is quantitatively the largest substrate source for gluconeogenesis, especially in the kidney. The liver uses both glycogenolysis and gluconeogenesis to produce glucose, whereas the kidney uses only gluconeogenesis. After a meal, the liver switches to glycogen synthesis and the kidneys increase gluconeogenesis. The intestine primarily uses glutamine and glycerol.
Define substrate-level phosphorylation, and how compounds capable of this process are chemically generated. Provide a specific example of a compound capable of substrate-level phosphorylation and where this compound is utilized.
Answer:
Describe some of the functions of glycosaminoglycans and proteoglycans.
Answer:
There are many different monomeric dietary carbohydrates, such as galactose and fructose; however, there is only one glycolysis cycle which utilizes glucose as its substrate. How are these other carbohydrates metabolized?
Answer:
Prothrombin, linked to membranes, is proteolytically activated to establish blood clotting. What events happen that take prothrombin and deploy this enzyme to establish blood clotting?
Answer:
High energy intermediates (other than ATP) are used to store energy during intermediate stages of product synthesis. Provide an example of such a high energy intermediate used in synthesis, and discuss how the product synthesis makes use of this intermediate.
