1. Biochemistry of Life (Part I) Flashcards
What is human nutrition?
Making sure that our composition (from a molecular to an organismal level) is functioning properly
Why do cells require ATP for maintenance?
Resting cells still require ATP to maintain their cellular structures through cell division, which utilizes energy and, thus, needs nutrients
What nutrients are necessary during cell division?
- Energy
- Proteins to create new structures and motors
- Lipids to create cell membranes
Define nutrigenetics.
Genes control the metabolism of nutrients
Define nutrigenomics.
Nutrients influence the expression of genes
What happens if lactose is present in the culture media of E. coli?
Induction of the gene (lac operon) involved in lactose metabolism
Explain how the nutrient-gene interaction between lactose and the lac operon gene is a homeostatic mechanism.
You don’t want to waste your energy to produce enzymes for metabolizing lactose, if there is no lactose to metabolize in the first place
Explain what happens on a molecular level to the lac operon when there is a lack of lactose.
- lacI encodes the repressor protein
- The repressor protein binds to the lac operator, present in the promoter region of the lac operon
- This ultimately shuts down the transcription of the operon
Explain what happens on a molecular level to the lac operon when there is lactose.
- Lactose binds to the repressor protein, which causes a conformation change
- The changed repressor is unable to bind to the lac operator region
- RNA polymerase can see the promoter, and make RNA for the lacZ, lacY, and lacA regions (genes known for their role in lactose metabolism)
What are the three genes that are known to be involved in the metabolism of lactose?
- B-Galactosidase
- Permease
- Transacetylase
Lactose is an example of a ______________, while the lac operon is an example of a _____________.
dietary constituent
responsive gene
What is a responsive gene?
- Either be induced or repressed by a dietary constituent
- If it does not do either, it is not a responsive gene
What do secondary mediators have an impact on in nutrient-gene interactions? What are they affected by?
- They have an impact on their own responsive genes
- They are indirectly affected by dietary constituents
What are the five ways dietary constituents can interact with genes, either directly or indirectly?
- Responsive genes (direct)
- Physiological modulation (indirect)
- Regulation of transcription
- Regulation of translation
- Modification of proteins
Where do responsive genes reside in Eukaryotic cells? What about in Prokaryotic cells?
- Eukaryotic: nucleus
- Prokaryotic: nucleoid body
Explain how amino acids and fatty acids regulate gene expression indirectly.
- Interact with a protein embedded on a cell membrane, which will initiate a signal transduction pathway (e.g. phosphorylation-chain)
- When the signal reaches the nucleus, the protein interacts with a promoter region of a gene to induce or repress RNA transcription
Explain how fat-soluble vitamins, trace elements, fatty acids, phytochemicals, and sterolsregulate gene expression.
- Find their way inside the cell through nutrient transporters
- Interact with specific transcription factors
- Nuclear receptors act on target genes, affecting transcription
Explain how folic acid, vitamin B12, and methionine regulate gene expression.
- Affect DNA methylation
- Impacts the ability of the cell to utilize genetic information
- Renders it unaccessible for transcription
Explain how cofactors and vitamins regulate gene expression.
Translation cannot occur if they are not present
Explain how nutrients can affect proteins directly.
- Certain proteins find their way inside the cell and interact directly with proteins and enzymes
- This affects their conformation, their binding capacity, and their interactions
- These influence metabolism by either increasing or decreasing efficiency
Concerted Regulation of Protein and Lipid Biosynthesis occurs by which pathway?
The Akt/mTORC1 pathway
What are the four proteins involved in the Akt/mTORC1 pathway?
- AMPK
- Akt
- mTORC1
- SREBP
AMPK and Akt are components of a signalling pathway. What are their functions?
- AMPK: responds to cellular energy status
- Akt: responds to growth factors, including insulin
What is the role of mTORC1?
- Integratesthe information related to the kind:
- Nutrients available
- Cellular energy status,
- Growth factors interacting with the cell receptor
What does the Akt/mTORC1 pathway affect?
Regulates protein and lipid biosynthesis
True or False: if you increase your mass of cells, you increase your lipid content. Why or why not?
- True
- Due to the Akt/mTORC1 pathway, which regulates cell growth through protein AND lipid biosynthesis
Why is glucose uptake necessary for the Akt/mTORC1 pathway?
Since the production of protein and lipid biosynthesis is an energetically expensive process, which requires the production of ATP through glycolysis and the TCA cycle
What is SREBP responsive to?
To the status of cholesterol in the environment
Explain what happens to SREBP when you have low sterol concentrations.
- SREBP, interacting with SCAP and COPII, migrates from the ER towards the Golgi
- At the Golgi, the SREBP protein is processed by specific proteases of the Golgi
- The proteases liberate a portion of SREBP, which migrates to the nucleus and binds to the Sterol Response Element (SRE)
- SRE stimulates the target genes involved in cholesterol and fatty acid biosynthesis
Explain what happens to SREBP when you have high sterol concentrations.
- SREBP remains bound to SCAP, which is bound by INSIG, and remains in the ER
Give examples of abundant elements.
Carbon, hydrogen, nitrogen, oxygen, phosphorus
Give examples of trace elements.
Calcium, chlorine, cobalt, copper, iodine, iron, manganese, magnesium, potassium, sodium, sulphur, selenium, zinc
Are there few or many functional groups?
Few (12) functional groups composed of reorganized elements exist
Describe the 6 levels of organization of life.
- Macromolecule
- Supramolecular Assembly
- Organelle
- Cell
- Tissue
- Organ
- Organism
What are the two requirements for life?
- Energy: light, heat, chemical
- Raw materials
What raw materials are necessary for life?
- Carbon source
- Nitrogen source (protein and DNA)
- Water
- Oxygen
- Salts
Which terminal of an amino acid corresponds to the 5’-end of the gene that encodes it? What about the 3’-end?
- N-terminal (+) = 5’
- C-terminal (-) = 3’
What is hydrolyzed protein used for?
- Common in some large scale food manufacturing
- Texturizer, flavour enhancer
Explain how hydrolyzed proteins may be hypoallergenic.
If you break up a protein, our immune system might not recognize its different three-dimensional structure
What is the function of glutamic acid as a neurotransmitter?
Involved in long-term potentiation (learning and memory)
What symptoms has MSG been suggested to cause?
- Headaches
- Numbness
- Tingling sensations
- Obesity
What are the three kinds of MSG manufacturing? Are they L or D amino acids?
- Hydrolysis of proteins (L-amino acids)
- Chemical synthesis (DL-glutamate; synthetic)
- Fermentation (L-glutamate)
How does L-glutamate made by chemical synthesis differ from L-glutamate made by fermentation?
They are the same despite chemical synthesis being synthetic
Which foods contain MSG?
- Anything that contains “protein hydrolysate” (prepared foods, protein supplements)
- Fermented food products (soy sauce, Worcestershire sauce, vegemite)
Define homeostasis.
- Homeostasis occurs when the rate of input is equal to the rate of output
- Disease states occur when there is dysregulation in homeostasis
What is gout? What is the cause?
- A painful genetically-predisposed disorder characterized by joint inflammation.
- Caused by high uric acid concentration in the body due to high production or inefficient disposal of uric acid.
Is RNA or DNA easier to degrade?
RNA is easier to degrade; DNA is sequestered in the nucleus anyways
Explain how high uric acid concentration leads to the irritation and inflammation of joints.
Leads to the formation of uric crystals
Why is gout aggravated by an animal-based diet?
- They contain a higher proportion of purines (nucleic acids) than plant-based diets
- By unit-mass, there is more DNA compared to plant-based diets
What is uric acid synthesized from in humans?
Adenine and guanine
How do lipids differ from other macromolecules?
- They are not defined as polymers, but detain a functional classification
- Lipids are all hydrophobic molecules (fatty acids, cholesterol) and do not have a common subunit
What are the two sections of fatty acids?
- Carboxyl-end (hydrophilic)
- Methyl-end (hydrophobic)
Describe the varying lengths of fatty acid chains.
- Short-chain (2-6 carbons)
- Medium-chain (8-10 carbons)
- Long-chain (12-20 carbons)
- Very long-chain (>20 carbons)
How does palmitic acid compare to stearic acid?
Palmitic (16:0) is bad, stearic acid (18:0) is better
What is olive oil rich in?
Oleic acid (C18:1)
What is safflower oil rich in?
Linoleic acid (C18:2)
What is lard and beef tallow rich in?
Palmitic (C16:0) and stearic (C18:0) acids
What are the dangers of trans fatty acids?
- Mimic the structure of saturated fatty acids
- Body does not know how to metabolize these structures, so they are unknown to the body
- Their shape is different, thus, they do not fit the proper configuration in the enzymes
What are the three different uses of fatty acids?
- Energy source
- Structural component
- Substrate for the synthesis of signalling molecules
Describe myristillation.
- Covalent modification of proteins
- Attach myristic acid to a portion of a protein residue, which renders it hydrophobic
- It will tend to insert its hydrophobic residue in a membrane, along with the attached protein
Why can phosphorylation active enzymes?
- Conformational changes
- Serine/threonine/tyrosine become much more hydrophilic, which will pull out that region of the protein, and ultimately changes the shape
Why is fat a good energy source?
- They are highly reduced molecules, meaning they have lots of available energy.
- Their hydrophobic nature serves as good packing energy.
How are fatty acids stored?
In triacylglycerols
Is cholesterol a fat?
No, because solid fats and liquid oils are made of triacylglycerols
Differentiate saturated and unsaturated fatty acids.
- No double bonds; can be packed tightly; solid at RT
- One or more double bonds; can’t be packed; liquid at RT
Are all fatty acids the same within one TG?
They can be, but they can also be different
Describe the structure of phospholipids.
- Phosphate attached to a unique head group (X)
- Glycerol backbone
- Two fatty acids
How can phospholipids arrange themselves in water?
- Micelles
- Lipid bilayer
Give examples of interactions occurring within the lipid bilayer.
- Integral membrane proteins
- Peripheral membrane proteins
- Glycoproteins
- Carbohydrate side chains of glycoproteins
What are nuclear pores necessary for?
- Proteins
- RNA
- Nutrients
What is the role of phospholipases?
- Release fatty acids
- Leaves you with a lysophospholipid (missing a fatty acid)
What is the driving force of the increasing prevalence of both obesity and undernutrition?
- The composition of the foods we eat (fast foods, convenience foods)
- Altering the nutrient content to make cheaper sources
- Decrease in nutrient diverse
- Alteration in macronutrient content
What disorder is responsible for most deaths associated with a high body-mass index?
- Cardiovascular diseases
- Lipid deposition in arteries and complicating disorders
Describe the trends of sugar consumption over the past years.
- Increasing overall
- Decrease in sugar
- Increase in High-Fructose Corn Syrup (HFCS)
Give examples of foods sweetened with HFCS.
- Ketchup
- Energy bars
- Ice cream
- Soda
- Chocolate milk
What are the major contributors to the development of metabolic syndromes?
- Excessive caloric intake
- Poor quality nutrition (HFCS)
- Sedentary lifestyle
Give examples of acquired metabolic syndromes.
- Obesity
- Atherosclerosis
- Fatty liver disease
- Gallstones
- Hypertension
- IBD
- Diabetes
What does the sentence “food components are bioactive” mean?
- Nutrients are not solely needed to build muscle, bone and energy
- Nutrients are a part of what makes cells work, regulate their activity, and are the components of what they are made of
Do plant-based foods have cholesterol?
No, they have sterols
What is particular about plant-based sterols?
They are poorly absorbed because transporters are configured to solely recognize cholesterol
What is needed to synthesize cholesterol?
- HMG-CoA reductase
- The quantity of HMG-CoA reductase is a rate-limiting enzyme, which dictates the efficiency of the pathway
What is the function of statins?
Inhibit HMG-CoA reductase, and blocks cholesterol synthesis
________ is a lipid that is a precursor of highly bioactive molecules.
Cholesterol
Can cholesterol be oxidized to produce energy?
No, ATP spent synthesizing this molecule cannot be recovered
Cholesterol is a substrate for the synthesis of what?
- Steroid hormones
- Vitamin D
- Bile acids
What is cholesterol required for?
- The control of membrane fluidity
- Required for proteins to move and undergo conformational changes, respond to temperature changes, and allow substances to pass through
Cholesterol is a highly bioactive molecule that needs to be regulated to be kept within an optimal range. What homeostatic mechanism occurs when there is too much cholesterol?
- Cholesteryl esters (inactive) are synthesized and stored in an oil droplet
- Choleseteryl esters can’t be used to make steroid hormones or bile acids
- They need to be converted to cholesterol to become bioactive again
Define a nutrient.
A nutrient is either a chemical element or compound that is used in the metabolic processes of, or forms an integral component of the physiology of an organism
What are macronutrients?
- Needed in large quantities
- Carbohydrates, proteins, fat
- Nucleic acids are not a source of energy
What are micronutrients?
- Small quantities
- Vitamins and minerals
What is the criteria for nutrient essentiality?
That absence of the nutrient from the diet results in characteristic signs of a deficiency disease and these signs are prevented only by the nutrient itself, or a specific precursor of it
What are the essential amino acids?
- Valine
- Phenylalanine
- Histidine
- Leucine
- Methionine
- Tryptophan
- Isoleucine
- Threonine
- Lysine
- Arginine (in children and special cases; preterm infants are unable to synthesize or create Arginine internally)
What are the essential fatty acids?
- Fatty acids with double bonds located at positions 8 or less (counting from the methyl end)
- Linoleic acid
- Linolenic acid
What are the essential fat-soluble vitamins?
- A
- D
- E
- K
What are the essential water-soluble vitamins?
- B1, B2, B3, B5, B6, B7, B9, B12
- C
- Choline
What is vitamin A?
Retinol
What is vitamin D?
Ergocalciferol, cholecalciferol
What is vitamin E?
Tocopherol
What is vitamin K?
Naphthoquinoids
What is vitamin B1?
Thiamine
What is vitamin B2?
Riboflavin
What is vitamin B3?
Niacin
What is vitamin B6?
Pyridoxine
What is vitamin B5?
Pantothenic acid
What is vitamin B9?
Folic acid
What is vitamin B12?
Cobalamin
What is vitamin B7?
Biotin
What are the four functions of choline?
- Susbtrate for phosphatidylcholine biosynthesis
- Ensures the structural integrity and signaling functions of cell membranes
- Source of methyl groups
- Used to make a variety of very important metabolites (e.g. acetylcholine, platelet-activating factor, betaine)
What is the mechanism that spares choline when it is deficient?
The body will recover and reabsorb all the choline it secretes in the bile
Describe the de novo synthesis of choline.
- Three successive methylations (recovers methyl groups) of the phosphatidylethanolamine headgroup generates phosphatidylcholine
- Choline can be released from phosphatidylcholine
What are the essential macrominerals? What is their function?
- Calcium
- Chloride ion
- Phosphorus
- Important in forming active enzymes needed to support metabolism
What are phytochemicals?
- A broad and diverse group of plant-derived compounds
- Compound that you can’t find anywhere else other than plants
Which phytochemicals are thought to have beneficial effects on health? Are all phytochemicals good?
- Flavonoids
- No, some are very toxic
Define malnutrition.
- Refers to improper to insufficient diet
- Nutrient deficiency and nutrient excess
What are essential fatty acids substrates for?
A class of molecules called eicosanoids
Give examples of eicosanoids.
- Prostaglandins
- Leukotrienes
- Thromboxanes
What are the functions of essential fatty acids?
- Immune function
- Inflammatory response
- Blood clotting
- Vasodilation
- Kidney function
- Cognitive function
What are the consequences of essential fatty acid deficiency?
- Growth retardation
- Sparse hair growth, dry skin and scaling (excema)
- General weakness
- Depression
- Poor wound healing, increased susceptibility to infection
- Edema
- Vision problems
- Neurological problems (particularly in severe cases).
What are the consequences of essential fatty acid excess?
- Currently, does not appear to cause severe problems.
- May cause excessive bleeding (slow blood clotting)
What is the essential function of vitamin A?
Maintenance of epithelial cells
Vitamin A and other retinoids are ________. What does this mean?
- Teratogenic
- Disturbs the development of the embryo or fetus
Vitamin A is the ligand for which receptors? What happens if you supply too much vitamin A?
- Retinoic acid receptor (RAR) and retinoid x receptor (RXR)
- If you supply too much vitamin A, you inappropriately induce the expression of genes, which may cause damage
Where is vitamin A found? How does overdose usually occur?
- Coloured fruits and vegetables
- Difficult to overdose on fruits and veggies
- Overdose usually occurs with supplements and drugs (e.g. Acutane)
How does vitamin A deficiency lead to xerosis? What is xerosis?
- Abnormal dryness
- Causes mucus-secreting cells to be replaced by keratin producing cells
What is the consequence of vitamin A deficiency?
- Primarily affects eye function
- Eye blindness
- Eye xerosis causes ulcerations and leads to blindness
People with diseases involving the absorption of lipids are at risk for which deficiency?
Vitamin A
What are the consequences of vitamin A excess?
- Birth defects
- Reduced bone mineral density
- Weight loss, headache, vision problems, dry itchy skin, hair loss, anemia, teeth discolouration, enlarged liver and spleen
Is iron a macromineral or a micromineral?
- Transition metal
- Micromineral
What is iron’s main function?
- Used by a prosthetic group by many biologically important proteins (ex: heme groups of hemoglobin, myoglobin)
- Generally found in enzymes involved in carrying or metabolizing oxygen
How much iron does the average person contain? Where is it largely found
- 3-4 grams of iron
- 60% in the blood
What is the average intake of iron? What is the average absorption?
- 15 mg
- 2 mg
What % of the world is deficient in iron?
80
What individuals are at risk for iron deficiency anemia?
- Alcoholics
- Patients with infectious, inflammatory, or neoplastic diseases
What are the symptoms of iron deficiency anemia?
- Pale skin
- Tired and weakness
- Difficulty maintaining body temperature
- Shortness of breath
- Inflamed tongue
- Diminished cognitive function
- Decreased immune function
How does iron loss occur?
- Shedding of epithelial surfaces
- Through occult blood loss in the intestine
- Menstruation
- Lactation
What is the cause of secondary hemochromatosis?
- Excessive alcohol consumption
- Excessive use of dietary iron supplements
What other disorders can iron excess lead to?
- Arthritis
- Liver disease leading to liver failure
- Damage to the pancreas causing diabetes
- Cardiac function abnormalities
- Impotence
- Abnormal skin pigmentation (making it look grey or bronze)
- Thyroid deficiency
- Damage to the adrenal glands
Is iodine a macromineral or a micromineral?
- Halogen
- Micromineral
What are the major functions of iodine?
- Necessary for normal thyroid function
- Essential substrate for the synthesis of thyroid hormones
What are the functions of thyroid hormones?
- Control many aspects of energy (carbohydrate and fat) metabolism
- Ligands of TR receptor (transcription factor belonging to the nuclear receptor superfamily of transcription factors)
What are sources of iodine?
- Seafood (cod, sea bass, haddock, perch)
- Kelp
- Dairy products
- Iodized table salt
What are the consequences of iodine deficiency?
- Increased fetal and infant mortality
- Neurological defects
- Mental retardation (cretinism)
- Decreased reproductive fitness
- Hypothyroidism
- Goiter (hypertrophy of the thyroid gland)
What are secondary thyroid related disorders?
- Anemia
- Arthritis
- Eye enlargement and inflammation
- Hair loss and premature graying of hair
- Inflammatory bowel diseases
- Depression
What is the cause of goiter?
- Iodine deficiency; impaired by thyroid hormone synthesis
- Also caused by excessive iodine, which results in the inhibition of thyroid hormone production
Does an excess of iodine develop more or less problems than iodine deficiency?
Excess iodine develops less problems than iodine deficiency
What are the consequences of an excess of iodine?
- Skin ulceration (“kelp acne”, high incidence in Japan where kelp is consumed in large quantities)
- Impairs thyroid hormone production and causes goiter in response to decreased thyroid hormone concentration
What is the lacZ region associated with?
B-galactosidase
What is the lacY region associated with?
Permease
What is the lacA region associated with?
Transacetylase
What does the inhibitor protein of the lac operon bind to in order to shut down transcription?
lacO
How do statins function?
- By competitively inhibiting to HMG-CoA reductase
- Competitive binding to the active site of HMG-CoA reductase prevents HMG-CoA from binding to produce mevalonate
What binds to HMG-CoA reductase? What is produced?
- HMG-CoA binds
- Mevalonate is produced