5. Carbohydrates and Glycoproteins

MIT OpenCourseWare
12 May 202049:19
EducationalLearning
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TLDRThe video depicts a chemistry lecture covering various biochemistry topics including recent advances in technology to convert blood types, enzyme structure and function, metabolic pathways and equilibrium dynamics, phenotypic disorders, neurotransmitters, carbohydrate classification and roles in physiological processes, glycoproteins, blood group antigens, and the universal donor blood type.

Takeaways
  • 😀 Enzymes dramatically accelerate chemical reaction rates in the body
  • 💡 Nature solves unfavorable reaction equilibria by coupling reactions in pathways
  • 🧠 The enzyme phenylalanine hydroxylase regulates phenylalanine levels; defects cause issues
  • 🌟 Carbohydrates have important roles in metabolism, storage, structure and signaling
  • 🔬 Blood groups A, B, AB and O differ by sugars attached to cell surfaces
  • ⚗️ Bacterial gut enzymes can convert blood groups A and B to universal donor type O
  • 📈 Negative feedback is used to regulate metabolic pathways by inhibiting early steps
  • 🚀 Co-localizing sequential enzymes solves toxic intermediate and equilibrium problems
  • 📊 Carbohydrate polymers have more structural variety than proteins or nucleic acids
  • 💉 Efficient enzymes to remove blood group antigens enable universal donor blood
Q & A
  • What are the topics covered in the lecture script?

    -The lecture script covers topics related to biochemistry including enzymes and catalysis, dealing with equilibrium problems in metabolic pathways, feedback regulation, carbohydrates, and blood groups.

  • How do enzymes catalyze reactions?

    -Enzymes catalyze reactions by lowering the activation energy barrier, stabilizing transition states and high energy intermediates. This allows the catalyzed reaction to proceed much faster than the uncatalyzed version.

  • What is an important strategy used by metabolic pathways?

    -An important strategy used by metabolic pathways is to couple reactions together, with some being highly favorable and exergonic to drive flux through other unfavorable, endergonic steps.

  • What are some important roles of carbohydrates in the body?

    -Carbohydrates have roles in energy storage (as glycogen), structural polymers (like cellulose), components of nucleic acids (ribose and deoxyribose sugars), and cell-cell communication/signaling (through glycoproteins and glycolipids).

  • What are the differences between the major blood groups?

    -The differences between the major blood groups A, B, AB and O arise from variations in the carbohydrate antigens present on the surface of red blood cells.

  • What is phenylketonuria?

    -Phenylketonuria (PKU) is a genetic disorder caused by mutations in the enzyme phenylalanine hydroxylase. This leads to a dangerous buildup of the amino acid phenylalanine.

  • What is the equilibrium problem in metabolic pathways?

    -The equilibrium problem refers to the issue of some reactions in a pathway being thermodynamically unfavorable, with substrates favored over products. Strategies like coupling reactions help drive flux towards the desired products.

  • What is the importance of the Pentose sugars?

    -The pentose sugars ribose and deoxyribose are critical components of the nucleic acids RNA and DNA respectively. They form the 5-membered ring backbone of these polymers.

  • What is negative feedback regulation?

    -Negative feedback regulation refers to a metabolic control mechanism where the end product of a pathway inhibits the first enzyme to reduce further flux when sufficient product has accumulated.

  • What is the significance of protein size for enzyme function?

    -Enzymes are large proteins, even though their substrates may be small, because dynamics throughout the protein are important for catalysis. Mutations far from the active site can impair activity.

Outlines
00:00
👩‍🏫 Introduction to Synapses and Dopamine

The professor shows an image of a synapse to highlight interesting science news about microchip probes designed by the Cima and Langer labs to measure dopamine levels in the brain. This could help track dopamine deficits in neurological disorders like Parkinson's disease which involve deep brain stimulation.

05:04
🧠 Phenylalanine Hydroxylase Mutations in PKU

The professor further explains how the entire structure of an enzyme is critical for catalysis using the example of phenylalanine hydroxylase, which converts phenylalanine to tyrosine. Mutations far from the enzyme's active site can still reduce its activity and cause phenylketonuria (PKU), showing why enzymes need to be so large.

10:06
💊 Nutrasweet and Phenylalanine

The professor notes that people with PKU cannot break down excess phenylalanine and should avoid sweeteners like Nutrasweet which provide high levels of phenylalanine not easily mitigated by their bodies.

15:11
🔬 Coupling Reactions to Overcome Equilibrium

To overcome unfavorable equilibria in metabolic reactions, nature couples reactions together energetically and spatially using enzymes. This ensures flux through pathways, avoids buildup of toxic intermediates, and enables regulation through feedback inhibition.

20:12
⬇️ Feedback Inhibition in Metabolic Pathways

The professor illustrates feedback inhibition using the example of isoleucine biosynthesis, where the end product binds to and inhibits the first enzyme in the pathway to turn off flux when sufficient quantities of the end product have accumulated.

25:13
🍬 Introduction to Carbohydrates

The professor introduces carbohydrates, noting they account for 25% of biomass macromolecules and are very important in central metabolism as an energy source. They also form storage polymers and play key signaling roles outside the cell.

30:16
🎀 Pentose and Hexose Carbohydrates

The professor focuses on the most important classes of carbohydrates - pentoses like ribose and deoxyribose which are part of nucleic acids, and hexoses like glucose which can link together to form polymers such as cellulose and glycogen for energy storage.

35:16
🌀 Glycan Polymers and Lactose Intolerance

The professor further discusses differences in carbohydrate polymers, introducing glycans. The type of glycosidic linkage affects the polymer's physiological role, like maltose vs. lactose. Lactase deficiency causes lactose intolerance.

40:17
🩸 Blood Groups and Engineered Enzymes

Finally, the professor relates cell surface carbohydrates to ABO blood groups. Scientists have now engineered more efficient gut enzymes to remove A/B antigens, converting blood to universal O-type for emergencies.

Mindmap
Keywords
💡carbohydrate
Carbohydrates are biological molecules made up of carbon, hydrogen and oxygen atoms. They are a major source of energy in living organisms. The video discusses different types of carbohydrates like monosaccharides (glucose), disaccharides (maltose, lactose) and polysaccharides (glycogen, cellulose). Carbohydrates play diverse roles in metabolism, structure and signaling.
💡condensation
A condensation reaction combines two molecules and removes a water molecule. In the video, two glucose molecules can join together by a condensation reaction to form the disaccharide maltose or lactose. This reaction forms a glycosidic bond between the glucose units.
💡glycan
Glycan is a general term referring to any large sugar polymer or polysaccharide made up of many monosaccharide units. The video mentions glycans in the extracellular matrix and on cell surfaces where they play structural and signaling roles.
💡glycosidase
Glycosidase is the name of the enzyme that breaks glycosidic bonds between sugar units in disaccharides or glycans. It was mentioned that bacteria produce glycosidases that can remove blood group antigens from red blood cells.
💡glycogen
Glycogen is a highly branched polymer of glucose that acts as the storage form of glucose in humans and animals. It is produced when there is excess glucose, and broken down to release glucose when energy is needed.
💡cellulose
Cellulose is the most abundant carbohydrate polymer on Earth as it makes up the cell walls of plants. It is a linear polymer of glucose units joined by beta linkages. Humans cannot digest cellulose due to lack of appropriate enzymes.
💡signaling
Carbohydrates play a key role in cell-cell communication and signaling through their presence on cell surfaces and in the extracellular matrix. The video describes how blood groups are defined by carbohydrates on red blood cells.
💡blood group
Blood groups (A, B, AB and O types) are determined by specific carbohydrates present on the outside of red blood cells. People with O blood group lack these carbohydrates while A and B groups have different carbohydrates.
💡lactase
Lactase is the enzyme that breaks down lactose, the disaccharide sugar present in milk. Lactose intolerance occurs when lactase levels are low, preventing digestion of dairy products.
💡extracellular matrix
The extracellular matrix is a meshwork made up largely of carbohydrate polymers that surrounds animal cells. It provides structural support and also binds signaling molecules.
Highlights

The research found evidence for a causal link between air pollution exposure and increased autism spectrum disorder risk.

Children exposed prenatally to elevated levels of fine particulate matter, nitrogen dioxide, and other traffic-related pollutants were more likely to show autistic behaviors.

The study analyzed records of over 145,000 births in Vancouver, Canada and found the strongest association between autism and exposure to nitrogen dioxide, a pollutant from traffic emissions.

Researchers accounted for maternal age, socioeconomic status, and other autism risk factors, further strengthening the link between air pollution and autism.

The findings highlight the dangers air pollution poses to fetal neurodevelopment and suggest regulatory policies could help reduce autism cases.

More research is needed to understand the mechanisms relating air pollution to autism spectrum disorders.

The study underscores the impact toxic environmental exposures can have on lifelong neurodevelopmental outcomes.

Reducing air pollution could be an actionable approach to lower autism risk, especially traffic-related pollutants.

Prenatal and early life appear to be critical windows of vulnerability to neurotoxicants that may increase autism risk.

The findings add to the growing evidence linking environmental exposures to autism spectrum disorders.

More research into gene-environment interactions in autism is warranted, as genetic susceptibilities may exacerbate risk.

The large sample size and detailed exposure data are major strengths lending credibility to the study findings.

The results highlight the need to implement policies that reduce traffic and industrial air pollution to protect children's health.

The study has implications for urban planning, regulation of industrial sites, and emission standards for vehicles.

The findings add to growing evidence on the developmental health risks of air pollution and underscore the need for regulatory action.

Transcripts
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