Biochem So Far

Where is glycogen stored and what is the main purpose in each?

Mainly stored in the liver (purpose is to maintain glycogen in the blood) and muscle (energy used in muscle contraction).

What is the structure of glycogen?

Glycogen's core is glycogenin with alpha 1,4 linkages for the chain and alpha 1,6 linkages at the branch points.

What is glycogen phosphorylase and what does it do?

Glycogen phosphorylase is the main enzyme which degrades glycogen from the nonreducing ends.

What form of glucose is active and what converts it?

Glucose 1-phosphate is converted to glucose 6-phosphate by phosphoglucomutase.

Where is glycogen stored and what is the main purpose in each?

Glycogen is primarily stored in two locations: the liver and muscles. In the liver, glycogen serves the crucial purpose of maintaining blood glucose levels, helping to regulate energy availability in the body. In muscle tissue, glycogen provides readily accessible energy specifically for muscle contraction and overall physical activity.

What is the structure of glycogen?

Glycogen is a polysaccharide with a unique structure. Its core is a protein called glycogenin, which initiates glycogen synthesis. The main chains are formed by alpha 1,4 glycosidic linkages, while branching occurs through beta 1,6 linkages at various points, creating a highly branched and compact molecule essential for rapid mobilization.

What is glycogen phosphate and what does it do?

Glycogen phosphorylase, often referred to as glycogen phosphate, is the primary enzyme responsible for the degradation of glycogen. It works by cleaving glucose units from nonreducing ends of glycogen branches, releasing glucose-1-phosphate, which can then enter glycolysis for energy production.

What form of glucose is active and what converts it?

The active form of glucose in metabolism is glucose-6-phosphate. Hlucose-1-phosphate is converted by the enzyme phosphoglucomutase, which facilitates the interconversion necessary for energy metabolism or storage.

What are the limitations of glycogen phosphate and what are the workarounds?

Glycogen phosphorylase has specific limitations; it cannot cleave glucose units near branch points and is restricted to alpha 1,4 glycosidic bonds. To address this, the enzyme alpha 1,6 glucosidase acts on the alpha 1,6 linkages, effectively removing branched glucose units from glycogen.

What molecule is used in the synthesis of glycogen and what synthesizes it?

Uridine diphosphate glucose (UDP-glucose) is the key substrate used in the synthesis of glycogen. The enzyme UDP-glucose phosphorylase synthesizes this molecule from glucose-1-phosphate. The process becomes irreversible due to the hydrolysis of pyrophosphate, ensuring a committed step toward glycogen formation.

How is a glycogen chain made and what needs to start it?

A glycogen chain is initiated by the enzyme glycogen synthase, which transfers glucose from UDP-glucose to the fourth carbon of an existing glycogen chain, creating alpha 1,4 linkages. Glycogenin serves as a primer to start the chain; branching is then introduced by a branching enzyme that adds additional glucose units.

What forms of glycogen phosphate are there and how are they regulated?

Glycogen phosphorylase exists in two forms: the less active 'b' form and the more active 'a' form. These forms can exist in tense (T) and relaxed (R) states, it is the R state that is more active and preferentially catalyzes the breakdown of glycogen.

What forms are present in liver and muscle and what are their negative regulators?

In the liver, glycogen phosphorylase is in the A form and R state, ensuring rapid glucose release for bloodstream homeostasis. Glucose acts as a negative regulator, converting it from the R state to the T state. In muscles, the B form typically exists in the T state when energy is not required. AMP acts as a positive stabilizer of the R state during activity, while ATP and glucose-6-phosphate signal high energy and stabilize the T state.

What regulations activate phosphorylase kinase and what does this mean?

Phosphorylase kinase is activated by calcium ions (Ca2+) released during muscle contractions and by phosphorylation from Protein Kinase A (PKA). Activation of this enzyme leads to the conversion of inactive phosphorylase b to active phosphorylase a, enabling the breakdown of glycogen.

What glycogen regulation occurs with the hormones Glucagon and Epinephrine?

Both Glucagon and Epinephrine increase cyclic AMP (cAMP) levels, which activates Protein Kinase A (PKA). PKA then phosphorylates and activates phosphorylase kinase. This enzyme subsequently phosphorylates and activates glycogen phosphorylase, promoting glycogen breakdown to release glucose into the bloodstream.

What kind of regulation is done by insulin?

Insulin regulates glycogen metabolism by promoting the activation of protein phosphatase-1, which dephosphorylates glycogen synthase b to convert it into the active glycogen synthase form. Insulin also inhibits phosphorylase kinase and glycogen phosphorylase, preventing further glycogen breakdown and promoting storage.

What are the different types of diabetes?

Diabetes Type 1 is characterized by the autoimmune destruction of insulin-producing beta cells in the pancreas, resulting in little to no insulin production. In contrast, Type 2 diabetes involves insulin resistance, where the body's cells do not respond properly to insulin, often combined with an insulin deficiency.

What is the sum equation of glucose turning into glycogen?

The overall reaction for synthesizing glycogen from glucose is summarized as: Glucose + 2 ATP + Glycogen (n) + H2O -> Glycogen (n+1) + 2 ADP + 2 Pi, which highlights the energy investment and conversion process.

What are the different units of carbohydrates?

Carbohydrates can be categorized into various units: Monosaccharides, which consist of single sugar molecules; oligosaccharides, which are short chains of a few monosaccharides; and polysaccharides, which are large, complex carbohydrates made of many monosaccharide units.

What are monosaccharides and what is the most basic monosaccharide?

Monosaccharides are the simplest form of carbohydrates, appearing as aldehydes or ketones with at least three carbon atoms and containing two or more hydroxyl (-OH) groups. The most basic monosaccharide is glyceraldehyde, which is a three-carbon sugar.

What dictates D configuration?

The D configuration is shown by the carbon farthest from the ketone or aldehyde being asymetrical

What are reducing sugars and what are their significance?

Reducing sugars refer to those carbohydrates that can act as reducing agents due to the presence of a free aldehyde or ketone group. This property is important medically, as the presence of reducing sugars such as glucose in the blood can react with hemoglobin, forming glycated hemoglobin (A1c), which is a key marker for monitoring long-term glucose levels.

What makes alpha and beta glucose?

Alpha glucose and beta glucose differ in the positioning of the hydroxyl group attached to the first carbon atom. In alpha glucose, the -OH group is on the opposite side of the CH2OH group, while in beta glucose, the -OH group is on the same side.

What are the modifications that can be done to monosaccharides?

Monosaccharides can undergo various modifications, including the formation of ester linkages with phosphate groups; the creation of glycosidic bonds with hydroxyl groups (O glycosidic bonds) and amino groups (N glycosidic bonds); leading to more complex carbohydrate structures.

What is the significance of glucosinolates?

Glucosinolates are sulfur-containing compounds primarily found in cruciferous plants (like broccoli and kale). They contribute to the bitter taste of these plants and serve a protective function, deterring herbivores. Some glucosinolates can be converted to cyanide and other toxic compounds when plants are damaged.

How are oligosaccharides held together?

Oligosaccharides are linked by glycosidic bonds, with O glycosidic bonds (typically alpha 1,4) connecting the monosaccharides. These bonds allow oligosaccharides to function in various biological processes, including cell recognition.

What are the three major functions of carbohydrates?

Carbohydrates serve multiple important functions in biological systems: 1) They provide structural materials, contributing to the integrity of cell walls and tissues; 2) They act as energy storage molecules, releasing energy through metabolic pathways; 3) They serve as signaling molecules that help in cell recognition and communication.

What are the five most common polysaccharides and describe the linkages?

The five common polysaccharides include: 1) Starch, composed of branched amylopectin and unbranched amylose (plant energy storage); 2) Glycogen, a highly branched polymer for energy storage in animals; 3) Cellulose, a linear polymer of beta-glucose forming structural components of cell walls; 4) Chitin, made of N-acetylglucosamine, found in the exoskeletons of insects and fungi; 5) Peptidoglycan, which consists of alternating sugar units linked by peptide bonds, providing structural support in bacterial cell walls.

Why are carbohydrates good at providing structural support?

The beta 1,4 linkages are very strong, there are not a lot of enzymes that can break the beta 1,4 linkages, the materials they form are fibrous and exclude water (no enzyme penetration), and the absence of water makes hydrolysis very difficult.

Expand on amylose and amylopectin.

Amylose is a polysaccharide characterized by its linear, unbranched structure formed primarily by alpha 1,4 linkages, making it less soluble in water. In contrast, amylopectin is a branched form of starch that includes both alpha 1,4 linkages in its main chain and alpha 1,6 linkages at the branch points, allowing for quicker digestion.

What protein residues can carbohydrates be linked to and what kind of linkages?

Carbohydrates can be linked to specific amino acid residues in proteins: they can form N-glycosidic bonds with asparagine residues (via nitrogen), and O-glycosidic bonds with serine and threonine residues (via oxygen), modifying protein function and stability.

What is the significance of carbohydrates and human blood?

In human blood, carbohydrates define blood type through their glycosylation patterns. Type A blood has N-acetylgalactosamine (Nac), Type B has galactose, and Type O lacks active glycosyltransferase, making it a universal donor.

What are the three reasons why glucose is such an important molecule?

Glucose is vital for several reasons: 1) It is one of the simplest and most abundant sugars, readily available in prebiotic environments; 2) It is the most stable hexose, ensuring efficient energy storage and release; 3) It has a minimal tendency to non-enzymatically glycosylate proteins, which helps prevent damage to cellular components.

What are the two stages of glycolysis?

Glycolysis consists of two main phases: the first is the investment phase, where glucose is phosphorylated and split into two 3-carbon molecules through energy investment; the second is the payback phase, where these molecules undergo oxidation and substrate-level phosphorylation to produce pyruvate and ATP.

How is glucose trapped in the cell and by what enzyme?

Glucose is trapped in the cell through phosphorylation by the enzyme hexokinase, which adds a phosphate group to glucose, transforming it into glucose-6-phosphate, effectively preventing its exit from the cell.

What enzyme converts glucose 6-phosphate into the fructose form?

The enzyme phosphoglucose isomerase is responsible for converting glucose-6-phosphate into fructose-6-phosphate, facilitating its further metabolism in glycolysis.

What enzyme traps the fructose form and how/into what?

Phosphofructokinase (PFK) is the enzyme that phosphorylates fructose-6-phosphate into fructose-1,6-bisphosphate, effectively trapping it for further metabolic processes.

What happens to the 1,6 fructose bisphosphate (in detail of enzymes and to the end)?

Fructose-1,6-bisphosphate is split by aldolase into two molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP). DHAP is not directly utilized in glycolysis and is converted to GAP by triose phosphate isomerase, allowing both products to enter the glycolysis pathway.

What is characterized with a deficiency of triose phosphate isomerase?

A deficiency in triose phosphate isomerase leads to severe metabolic disturbances and is characterized by lethality and neurodegeneration due to the impairment of glycolysis and subsequent energy production.

What is the fate of GAP in glycolysis (2 steps) and the significance?

GAP is converted to 1,3-bisphosphoglycerate (BPG) by glyceraldehyde 3-phosphate dehydrogenase in a two-step process. This reaction produces an intermediate with high phosphate transfer potential, making BPG a key molecule for ATP generation.

What is the intermediate between GAP and 1,3 BPG?

The thioester intermediate that forms during the conversion of GAP to 1,3-bisphosphoglycerate stabilizes the transition state, effectively reducing the activation energy of the reaction and enhancing the likelihood of ATP production.

How is 1,3 BPG used to make ATP?

1,3-bisphosphoglycerate donates its high-energy phosphate group to ADP to produce ATP in a reaction catalyzed by phosphoglycerate kinase, which represents a substrate-level phosphorylation step in glycolysis.

How does 3 phosphoglycerate get turned into pyruvate?

3-phosphoglycerate is converted into 2-phosphoglycerate via phosphoglycerate mutase. This intermediate is subsequently transformed into phosphoenolpyruvate (PEP) by enolase, then pyruvate is formed along with ATP by the action of pyruvate kinase.

Why is PEP high in transfer potential?

Phosphoenolpyruvate (PEP) has high transfer potential due to the unstable enol form triggered by the presence of its phosphate group, making it an excellent substrate for ATP synthesis.

What is the sum of the reactions in glycolysis?

The overall reaction of glycolysis can be summarized as Glucose + 2 Pi + 2 ADP + 2 NAD+ -> 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O, illustrating the conversion of glucose into energy-rich products.

How much ATP is produced in glycolysis vs the sum?

In glycolysis, a net production of 2 ATP molecules occurs after considering the initial investment of 2 ATP (4 are produced but 2 are consumed), resulting in a net gain of 2 ATP.

What are the three fates of pyruvate?

Pyruvate can undergo several pathways: it can be converted into acetyl CoA for entry into the citric acid cycle, reduced to lactate to regenerate NAD+ under anaerobic conditions, or converted to acetaldehyde and then ethanol in alcoholic fermentation.

What are the steps of alcoholic fermentation?

During alcoholic fermentation, pyruvate is decarboxylated to acetaldehyde by pyruvate decarboxylase, releasing carbon dioxide. Subsequently, acetaldehyde is reduced to ethanol by alcohol dehydrogenase, regenerating NAD+.

What is the balanced equation of alcoholic fermentation?

The balanced equation for alcoholic fermentation is Glucose + 2 Pi + 2 ADP + 2 H+ -> 2 Ethanol + 2 CO2 + 2 ATP + 2 H2O, highlighting the conversion of glucose to ethanol with ATP production.

What are the steps for lactic acid fermentation?

Lactic acid fermentation involves the conversion of pyruvate to lactate by the enzyme lactate dehydrogenase, which is critical under anaerobic conditions.

What is the balanced equation for lactic acid fermentation?

The balanced equation for lactic acid fermentation is Glucose + 2 Pi + 2 ADP -> 2 Lactate + 2 ATP + 2 H2O, showing the net gain of ATP from glucose without oxygen.

What are the entry points for glucose for other sugars?

Different sugars can enter glycolysis through various pathways: galactose can be converted into glucose-6-phosphate, fructose in adipose tissue can also be converted into glucose-6-phosphate, and fructose in the liver can convert through DHAP and GAP.

Which enzymes are control sites for glycolysis?

Control sites for glycolysis include three key enzymes: hexokinase (regulates the initial phosphorylation of glucose), phosphofructokinase (PFK) (the main regulatory step), and pyruvate kinase (final step leading to ATP production).

At rest, what is the regulation of muscular glycolysis?

At rest, glycolysis in muscles is regulated by high-energy molecules like ATP and AMP, which inhibit phosphofructokinase (PFK) and pyruvate kinase. Glucose-6-phosphate serves as a negative feedback regulator for hexokinase.

In use, what is the regulation of muscular glycolysis?

During active muscle use, low-energy conditions stimulate phosphofructokinase (PFK) to enhance glycolysis. The presence of fructose-1,6-bisphosphate acts as a feedforward signal to activate pyruvate kinase.

What happens to pyruvate under aerobic conditions?

Under aerobic conditions, pyruvate is transported into the mitochondria, where it is converted into acetyl CoA by the pyruvate dehydrogenase complex, facilitating its entry into the citric acid cycle for ATP production.

How is pyruvate turned into Acetyl CoA and what kind of reaction is it?

Pyruvate is converted to acetyl CoA through a decarboxylation reaction catalyzed by the pyruvate dehydrogenase complex, which is an irreversible process that releases CO2.

What is the equation for the pyruvate to Acetyl CoA reaction?

The reaction equation for converting pyruvate to acetyl CoA is: Pyruvate + CoA + NAD+ -> Acetyl CoA + CO2 + NADH + H+, illustrating the decarboxylation and reduction steps.

Where does pyruvate processing occur?

Pyruvate processing takes place in the mitochondrial matrix, where pyruvate undergoes conversion to acetyl CoA before entering the citric acid cycle.

What is E1?

E1, known as pyruvate dehydrogenase, is the enzyme that catalyzes the oxidative decarboxylation of pyruvate, requiring thiamine pyrophosphate (TPP) as a coenzyme.

What is E2?

E2, or dihydrolipoyl transacetylase, is the enzyme responsible for transferring the acetyl group from the acetyllipoamide cofactor to coenzyme A (CoA) during pyruvate processing.

What is E3?

E3, known as dihydrolipoyl dehydrogenase, is the enzyme that regenerates oxidized lipoamide by facilitating the transfer of electrons to FAD, which is subsequently reduced to FADH2.

What are the three major steps of pyruvate processing?

The major steps in pyruvate processing include: 1) Decarboxylation of pyruvate to release CO2; 2) Oxidation of the remaining two-carbon compound to produce acetyl lipoamide; 3) Transfer of the acetyl group to CoA, yielding acetyl CoA.

Expand on the decarboxylation step.

During the decarboxylation step, E1 enzyme catalyzes the reaction where pyruvate combines with the ionized form of TPP, leading to the formation of hydroxyethyl-TPP and concurrent release of CO2.

Expand on the oxidation to formation of acetyl CoA.

In this step, E1 facilitates the oxidation of the hydroxyethyl-TPP and the transfer of the two-carbon fragment to E2, forming acetyl lipoamide, which is then converted to acetyl CoA by E2.

Expand on the reoxidation of dihydrolipoamide.

In the final step, E3 catalyzes the reoxidation of dihydrolipoamide back to lipoamide. This involves the removal of hydrogen atoms using FAD, followed by the transfer of electrons from FADH2 to NAD+, forming NADH.

What are the three enzymes and three coenzymes in pyruvate processing?

In pyruvate processing, the three key enzymes are: 1) Pyruvate dehydrogenase (E1); 2) Dihydrolipoyl transacetylase (E2); 3) Dihydrolipoyl dehydrogenase (E3). The coenzymes involved include TPP, lipoamide, NAD+, FAD, and coenzyme A (CoA).

What are the two fates of acetyl CoA?

Acetyl CoA has two main fates: it can enter the citric acid cycle, leading to the production of ATP and carbon dioxide, or it can be used in fatty acid synthesis for energy storage.

What causes the negative regulation of pyruvate processing?

High energy levels of ATP, NADH, and acetyl CoA serve as negative regulators of the pyruvate dehydrogenase complex, signaling sufficient energy supply and inhibiting further conversion of pyruvate.

What causes the positive regulation of pyruvate processing?

Pyruvate and ADP serve as positive regulators of the pyruvate dehydrogenase complex, indicating low energy levels and promoting the conversion of pyruvate into acetyl CoA.

How is PDH regulated by kinase and phosphatase?

Pyruvate dehydrogenase is regulated by a kinase that adds a phosphate group, inactivating the enzyme, while a phosphatase removes the phosphate, reactivating pyruvate dehydrogenase.

What are the two key functions of the citric acid cycle?

The citric acid cycle performs two key functions: it harvests high-energy electrons in the form of NADH and FADH2 from acetyl CoA, and serves as a central metabolic hub, integrating various metabolic pathways.

What is the overview of the citric acid cycle and the two stages?

The citric acid cycle involves the oxidation of two-carbon units, resulting in the release of two molecules of CO2, formation of one ATP, and generation of NADH and FADH2. It consists of two stages: stage one focuses on oxidative decarboxylations, while stage two regenerates oxaloacetate and harvests electron carriers.

What are the steps of stage 1 of the citric acid cycle?

In stage 1, oxaloacetate and acetyl CoA are condensed into citryl CoA, which then forms citrate. Aconitase catalyzes citrate's conversion into isocitrate, which is subsequently converted to alpha-ketoglutarate by isocitrate dehydrogenase, generating NADH. Lastly, alpha-ketoglutarate is transformed into succinyl CoA and NADH by alpha-ketoglutarate dehydrogenase.

What inhibits aconitase and what is its significance?

Aconitase is inhibited by compounds such as fluoroacetate found in some plants, which disrupts the citric acid cycle, leading to energy production impairment and serving as a pesticide.

What are the steps of stage 2 of the citric acid cycle?

In stage 2, succinyl CoA is converted to succinate via succinyl CoA synthase, which produces ATP. Succinate is then converted to fumarate by succinate dehydrogenase (producing FADH2), fumarate is converted to malate, and finally malate is oxidized to regenerate oxaloacetate with NADH production.

What is the substrate level phosphorylation found in succinyl CoA synthase?

Substrate-level phosphorylation occurs when orthophosphate displaces CoA from succinyl CoA, forming succinyl phosphate. A histidine residue temporarily holds this phosphate, which is then transferred to ADP to generate ATP.

How much ATP does NADH and FADH2 generate per molecule?

Each NADH molecule generated during cellular respiration contributes approximately 2.5 ATP, while each FADH2 yields about 1.5 ATP, reflecting their roles in the electron transport chain.

What is the sum equation of the citric acid cycle?

The overall reaction for the citric acid cycle can be summarized as: Acetyl CoA + 3 NAD+ + FAD + ADP + Pi + 2 H2O -> 2 CO2 + 3 NADH + FADH2 + ATP + H+ + CoA, representing the process of converting acetyl CoA into energy-rich products.

How is the citric acid cycle regulated?

Regulation of the citric acid cycle primarily occurs at isocitrate dehydrogenase, which is positively activated by ADP, and at alpha-ketoglutarate dehydrogenase, negatively regulated by succinyl CoA. Additionally, both are inhibited by high energy levels indicative of ATP and NADH.

What other ways can oxaloacetate and acetyl CoA be replenished in the citric acid cycle?

Oxaloacetate may be replenished by converting pyruvate with pyruvate carboxylase during exercise, while acetyl CoA can be produced by the breakdown of fatty acids, demonstrating the cycle's integration with broader metabolic processes.