1. Biochemistry of Life (Part II) Flashcards
Give an example of how an optimal level exists for each nutrient.
- Goiter appears when there is iodine deficiency as well as excess
- The pathways that lead to goiter are different in terms of deficiency and excess
How do fatty acids impact signal transduction pathways?
If the composition of membranes is changed, the protein signalling in the membrane might be restricted
Give an example of how vitamin A influences gene expression.
- Is internalized and influences transcription factors
- Deficiency: blindness
- Excess: birth defects
What is the true cause of obesity?
- While increased macronutrient intake is one true cause, the opinions vary based on the source
- Singling on one type of food or nutrient might cause important discoveries (ex: vitamin A), but it does not give the whole picture when it comes to obesity
What did the “Patterns of Sedentary Behavior and Mortality in US Middle-Aged and Older Adults” demonstrate?
- 8000 adults (prospective cohort study)
- Analyzed excessive sedentary time and how this impacts quality of life
- Associated with a high-risk of OVERALL mortality, not just obesity
What causes an increase in energy input?
- High fat, energy dense foods
- Palatable, low-cost, easily available foods
- Large portion sizes
What causes a decrease in energy output?
- Decrease in work-related physical activity
- Decrease in activity of daily living
- Increase in sedentary behaviour
Why isn’t there a single factor that causes obesity?
- Because we have different genes that alter our susceptibility
- Because we are free to intake as many calories as we want
- Because we are free to dictate our rate of expenditure
How can obesity be caused socially?
- People that are overweight tend to hang out with other people who are overweight; perhaps, worsening their habits
- Also, commensal bacteria can be passed on socially
- When we alter the proportion of microorganisms that we live with, we tip off the beneficial balance, which may render it pathogenic
What study demonstrates that commensal bacteria (gut microbiota) may influence metabolic status and the state of adiposity?
- Microbiota transplant from an obese twin renders the recipient mouse obese
- Microbiota transplant from a lean twin renders a mouse lean
How many adipocytes are we born with? What happens to them?
- We are born with few white adipocytes
- The body makes more from stem cells when energy needs to be stored
What are the functions of white adipocytes?
- Take up excess fatty acids
- Synthesize fats
- Store them within the adipocytes’ cytoplasm
Why is a long-term lifestyle change necessary to get rid of white adipocytes?
- We can burn stored energy and shrink these adipocytes
- But, they have a 2-year half-life (long-lived)
What is atherosclerosis?
- Lipid, mostly (if not exclusively) cholesterol, deposition within the arteries
- Decreases the opening of the arteries
- Leads to a heart attack or stroke
What is one of the biggest risk factors for atherosclerosis?
High concentration of (LDL)-cholesterol in the blood
What is cholesterol produced by? What products contain cholesterol?
- By the liver
- Meat and dairy products
Does the intake of cholesterol affect your blood cholesterol?
- Well, cholesterol is usually only partially absorbable
- It is easier to intake cholesterol with fat, as they dissolve and travel with them
- Thus, individuals with high-fat diets absorb more cholesterol
Why is the cholesterol from food “extra” cholesterol?
Every single cell in the body has the capacity to make their own cholesterol
What does the “Red meat + wrong bacteria = bad news for the heart” study demonstrate?
- L-carnitine, present in meat, negatively influences cholesterol metabolism and increases the risk of atherosclerosis
- A regular diet of meat encourages the growth of bacteria that turns L-carnitine into TMAO (compound responsible for alteration in cholesterol metabolism)
What do variations in bitter taste receptors determine?
- How an individual perceives bitter taste
- Dictates (past acquired cultural tastes), an individual’s taste
Describe how the bitter taste bud receptor works.
- Taste receptor protein (TAS2R) interacts with a bitter taste molecule
- Causes a conformational change in TAS2R
- Interacts with a G-Protein (hydrolysis of cGMP)
- Calcium flows from the inside to the outside of the cell in an ion channel
- Signal transduction to the brain signals bitter taste
Explain why an individual would find a certain food more bitter than another.
If an individual’s TAS2R protein receptor has a higher affinity to bitter ligands, they will bind at much lower concentrations, thereby increasing their sensitivity
Why are we able to detect sweetness from aspartame?
Because the structure of the protein can interact with the structure of the sweet receptor
What gene encodes lactase? What is special about it?
- LCT gene
- It normally shuts down after weaning
What allows the LCT to not be shut off in certain cases?
- Polymorphism
- Lactate continues to be produced
- These individuals have access to the nutrients of dairy products
What can gene variations influence?
- Can determine whether specific classes of nutrients will have a change in regulating metabolic function
- Can provide individuals’ use of nutrients that are normally only accessible during specific periods of the life cycle
Where do the polymorphisms that cause lactase to be produced in adults occur?
- Not in the LCT gene itself
- In a neighbouring gene (MCM6 gene)
What are SNPs? What are they associated with in lactase?
- Single-nucleotide polymorphism are point mutations
- Associated with lactase persistence
What do we use instead of the word mutation? Why?
- We don’t know what normal is
- Polymorphism
What is the result of polymorphisms in the MCM6 gene?
Part of a regulatory domain that controls the expression of that portion of the genome, not necessarily just the LCT gene
Most of the genome is composed of what?
Regulatory elements
What are the roles of regulatory elements in our genome in terms of nutrition?
- These regions of DNA sense information about nutrients (quantity, type)
- In order for them to maintain peak metabolic capacity
What are hypersensitive regions? Should they be there?
- Technically, there should be no hypersensitive regions of DNA once it is wound with histones, but there are
- These regions are more sensitive to degradation by DNase
What has an impact on hypersensitivity?
Methylation of DNA
What gene is thought to be responsible for the absorption of dietary cholesterol in the intestine?
NPC1L1
What can cholesterol import be inhibited by? How?
- Ezetimibe
- A drug that interacts with NPC1L1
How can receptors be specific to a certain molecule?
- The structure, shape, and overall conformation of the molecule
- Amino acid side chains dictate the structures of the proteins
What is Calnexin?
- Protein that is used as a loading control (standard protein)
- Present in cells at around the same amount; does not vary from person to person
- Thus, we can normalize the amount in electophoresis
How many forms of the NPC1L1 gene do we have?
Humans have two forms: one from mother and one from father
What is SREBP-1C function tightly linked to?
Nutrient status
What have the SNPs in SREBP-1C variants been associated with?
Impaired plasma glucose control and increased risk for diabetes
Why is SREBP-1C odd?
- Responsive and regulates cholesterol metabolism (most relevant)
- Yet, the variations are associated with impaired plasma glucose control
What can loss of sensitivity to nutrient cues result in?
Inappropriate metabolic response to nutrient availability or deficiency
What does the severity of acquired metabolic syndromes depend on?
Different combinations of individual “gene variants”
What activates Akt?
1) Growth factors bind to RKT
2) Activates PI3K
3) Generates PIP3
4) Activates Akt through phosphorylation
What does activated Akt promote?
- Glucose uptake (GLUT4)
- Enhances glycolysis
- Enhances amino acid uptake
- Enhances stability of mature SREBP via inhibition of GSK3
What does Akt stabilize? How?
- Mature SREBP
- Via inhibition of GSK3
What is the consequence of manipulating ER calcium?
Causes the re-distribution of a portion of the intracellular unesterified cholesterol to a pool that is NOT available to the SCAP-SREBP complex
How did the SREBP processing pathway change through the manipulation of calcium in the ER?
- The SREBP processing pathway in ER Ca2+ depleted cells remained fully functional and responsive to changes in cellular cholesterol status
- Reduced ER Ca2+ shifts the distribution of cholesterol within the ER to a pool that is not directly accessible to the components of the cholesterol sensing mechanism.
What dictates the intracellular distribution of cholesterol?
ER calcium
What are the SREBP target genes?
- Fatty acid synthase
- HMG-CoA reductase
- HMG-CoA synthase
- Causes cholesterol and lipid biosynthesis
What are the aliphatic amino acids?
- Glycine
- Alanine
- Valine
- Leucine
- Isoleucine
What is the cyclic amino acid?
Proline
What amino acids contain sulfur groups?
- Cysteine
- Methionine
What amino acids contain hydroxyl groups?
- Serine
- Threonine
- Tyrosine
What are the aromatic amino aicds?
- Phenylalanine
- Tyrosine
- Tryptophan
What are the basic amino acids?
- Histidine
- Lysine
- Arginine
What are the acidic amino acids (and their amides)?
- Aspartic acid
- Glutamic acid
- Asparagine
- Glutamine
What links nucleic acids together?
Phosphodiester bonds
Where does most sodium come from?
Processed and restaurant foods
What kind of cells synthesize cholesterol?
Animal cells
What is required for the synthesis of cholesterol?
- Energy
- HMG-CoA reductase
What are the typical functions of vitamins and minerals?
Co-substrates, or enzyme co-factors, which determine enzymatic activity
Which essential amino acid is conditionally essential? In which cases?
- Arginine
- Preterm infants are unable to synthesize or create arginine internally
What TYPE of fatty acids can humans NOT synthesize?
Fatty acids with double bonds between carbons located at position 8 or less (counting from the methyl end)
Iron is used as a prosthetic group by many biologically important proteins. Give examples.
- Hemoglobin
- Myoglobin
- Cytochrome c
- Peroxidases
- Hydrolases
Where is iron generally found?
In enzymes involved in carrying or metabolizing oxygen
What genetic diseases cause iron toxicity?
- African hemochromatosis
- Porphyria
- Hyperferritinemia
- Hereditary hemochromatosis
What is secondary hemochromatosis caused by?
- Excessive alcohol consumption
- Excessive use of dietary iron supplements
What does excessive iodine result in?
- Goiter in response to decreased thyroid hormone concentration
- Results in the inhibition of thyroid hormone production
