Exam 3 Flashcards
What is the role of the pancreas?
It secretes insulin in response to rising blood glucose levels
What does the pancreas secrete for digestion and why is it important?
It secretes Trypsin, Chymotrypsin, Elastase. These are digestive proteases that degrade dietary proteins in the small intestine
What is the role of the small intestine in digestion?
It is where most of the absorption occurs. It absorbs nutrients, as well as secretes peptide hormones that control eating behaviors through neuronal signaling in the brain
What is the role of the large intestine in digestion?
It absorbs water and electrolytes
What is the stomach’s role in digestion?
It prepares food for the small intestine by producing chyme, an acidic food slurry.
It secretes peptide hormones that control eating behaviors through neuronal signaling in the brain
What is the Liver’s role in metabolism?
The central processing facility and metabolic hub.
It determines the dietary nutrients and metabolic fuels to peripheral tissues.
Why is the liver called a glucose regulator?
It removes excess glucose from the blood when carb levels are high. Relies on signaling from insulin and glucagon
What is the portal vein?
It directly delivers nutrients from the small intestines to the liver so it can inactivate toxins from the diet
What are the 4 different fates for Glucose-6-Phosphate?
1.Converted to glucose and released into the blood
2.Converted to Fructose-6-P that goes thru glycolysis to form pyruvate and then acetyl CoA. From there, lipid synthesis, oxidative phosphorylation, or ketogenesis
3. Converted to 6-phospho-gluconolactone and sent to the PPP
4. Converted to Glucose-1-P and used in glycogen synthesis
What is the purpose of skeletal muscle in metabolism?
Skeletal muscle uses fatty acids, glucose, and eventually ketone bodies for energy. These muscles are utilized in rapid bursts or endurance activities. In times of starvation, they can be used as an energy source
What is the purpose of cardiac muscle in metabolism?
Cardiac muscle uses mostly fatty acids and ketones for energy, It is continually used over the course of your life. Uses aerobic respiration for energy
What is creatine kinase?
A reversible enzyme that creates phosphocreatine when the cellular ATP levels return to normal during muscle recovery.
What is phosphocreatine?
Storage molecule for potential ATP. When acted on by creatine kinase, produces creatine and ATP that can be used for energy.
What is the purpose of adipose tissues?
It secretes peptide hormones (adipokines) to regulate metabolic homeostasis
It makes up 15-25% of an individuals mass
What is subcutaneous fat?
It is located in the thighs, butt, arms, and face. More for insulation and protection.
What is visceral fat?
Located in the abdomen. Secretes adipokines. More visceral fat gives rise to a higher risk of cardiovascular disease
What is BMI?
Provides an estimation of total body fat in an average person.
It provides on measure of risk
How does the brain relate to metabolism?
It is the control center of our bodies. 20% of the O2 consumed by the body is used for oxidative phosphorylation.
Generally depends mostly on glucose- 60% of body’s glucose is used by the brain.
fatty acids does not cross BBB but ketone bodies can
What is the blood brain barrier?
Area between the brain and the capillaries that limits what molecules transverse into the brain. There are certain areas where it is less restrictive like the pineal gland for melatonin or the posterior pituitary for oxytocin and ADH
What is PET imaging?
Positron emission tomography
Uses metabolic radioactive 18F-deoxyglucose to show differences in glucose metabolism
Used to detect blood flow for tumor visualization
Tau and amyloid deposits and neurodegenerative diseases
-epilepsy, cancer, heart disease
How does PET imaging work?
Positron emitted, generates gamma rays, which are detected by the scanner.
Positron is a subatomic particle with the same mass as an electron but with a positive charge
It is an anti-electron and when it collides with an electron both are converted to energy in the form of photons
Positron emission occurs with natural isotopes
What is the role of the kidneys?
They are located on either side of the abdominal cavity
only other major organ that uses gluconeogenesis
Remove concentrated levels of urea, ketone bodies, and soluble metabolites
What is hemodialysis?
blood is filtered from a patient with poor kidneys to remove waste products
What is metabolic homeostasis?
The process of maintaining optimal metabolite concentrations and managing chemical energy reserves in tissues
What are the 6 vital tissues?
Brain, liver, cardiac muscle, skeletal muscle, adipose tissue, heart
What is the triacylglycerol cycle?
An interorgan process that continually circulates fatty acids and triacylglycerols between adipose tissue and the liver
Maintains energy-rich fatty acids in circulation so that they can be used by peripheral tissues
What are the two components that depend of G3P?
Systemic and intracellular
What is the role of Insulin?
Released by pancreatic beta cells
stimulates glucose uptake in the liver, skeletal muscle and adipose tissue
Activates glycogen and FA synthesis
Decrease appetite through neuronal signaling
What is the role of glucagon?
Released by pancreatic alpha cells
stimulates gluconeogenesis
stimulates glycogen degradation
Stimulates fatty acid export from adipose tissue when food is not available
What is the islet of langerhans?
A collection of cells that produce insulin, glucagon. Also has capillaries connected
What is PPAR signaling?
Peroxisome-proliferator-activated receptor (PPAR) nuclear receptor proteins
They are metabolic sensors of lipid homeostasis
It regulates gene expression in response to binding of low-affinity, fatty acid derived nutrients
important in energy metabolism and insulin sensitivity
What is the metabolic fuel during starvation?
Blood glucose levels are maintained by degradation in liver glycogen
Flux is altered in two ways:
gluconeogenesis occurs
fatty acids are used as fuel
What are the changes in metabolism during starvation?
Fatty acid release
increase in gluconeogenesis
increase in ketogenesis
protein degredation
What is the purpose of leptin?
It can decrease fat storage thru signaling pathways
What is metabolic syndrome?
Lifestyle of prolonged positive energy imbalance
Symptoms include:
Abdominal obesity
insulin resistance
hypertension
hyperlipidemia
high risk for cardiovascular disease
What is Type I diabetes?
Insulin dependent
insufficient insulin production by pancreatic beta cells, usually occurs earlier in life
What is Type II diabetes?
Insulin-resistant
Coupled with positive energy balance (weight gain)
Desensitization of insulin receptor signaling
What levels are high in adipocytes when lipid store are high?
TNF-alpha
What is the purpose of TNF-alpha?
It down regulates adiponectin and fatty acid metabolism genes as well as the inhibition of downstream insulin signaling
What are the 4 major classes of diabetes treatments?
- Alpha glucosidase inhibitors (miglitol)
2.Sulfonylurea drugs, which inhibit the dependent K+ channel (Glipizide)
3.Drugs that AMPK are stimulators (metformin)
4.Ligand agonists of the nuclear receptor PPARy (thiazolidinediones)
What does metformin promote in skeletal and cardiac muscle?
Fatty acid oxidation
glucose uptake
mitochondrial biogenesis
glycolysis
What are the three main factors that influence metabolic homeostasis?
Genetic inheritance
nutrition
exercise
What is the impact of maintaining a healthy weight?
It significantly lowers the risk of type 2 diabetes, CVD, and some types of cancer
What is ephedrine?
A drug used to induce weight loss
it stimulates adrenergic receptor signaling through the release of NE
What is Lorcaserin (belviq)?
Appetite suppressant (receptor agonists for serotonin)
First approved weight loss drug that targets neuronal control of food consumption and energy expenditure
What is Orlistat (xenical)?
A weight loss drug
pancreatic lipase inhibitor
triglycerides pass thru the digestive tract without being metabolized
What are some other weight loss methods?
Olestra which is a fat substitute in foods
Caloric intake reduction- different diets
What types of fat lead to higher LDL levels and an increased risk of CVD?
Saturated and trans fats
What types of fats lower your cardiovascular risk?
Poly-unsaturated and cis fats
What is the glycemic index?
A numerical value indicating how fast glucose is released unto the blood after eating carb containing foods relative to the rise in the blood glucose after drinking a solution of pure glucose
Foods <55 are considered healthy
High glycemic index foods are associated with drop in blood glucose levels leaving feeling lethargic and can cause insulin spikes
What are the components of eating a healthy plate?
Veggies, fruits, healthy proteins, whole grains, water, healthy oils
What are the metabolic effects of physical exercise?
Significant healthy improvements can be achieved by just 30 minutes of moderate exercise a day
Aerobic respiration is used for endurance sports while ATP and phosphocreatine and anaerobic respiration are used for quick bursts of energy
What are nucleotides used in?
energy conversion reactions
signal transduction pathways
coenzyme-dependent reactions
genetic information storage and transfer
What do nucleotides consist of?
a nucleotide base
a ribose ring
phosphoryl group
Which nucleotide bases have one ring?
Pyrimidines-cytosine, thymine, uracil
What nucleotide bases have 2 rings?
Purines- guanine and adenine
What is the most abundant nucleotide?
ATP!
What are the functions of ATP?
Energy conversion
Signal transduction
coenzyme function
genetic information
What is the nucleotide salvage pathway?
Used to resynthesizes nucleotide monophosphates from free bases
energy investment is not as high as the de novo pathway
PRPP is used
What is the common intermediate produced in purine metabolism?
inosine-5’-monophosphate (IMP)
How does purine synthesis differ from pyrimidine synthesis?
Purine- build the base on the sugar
Pyrimidine- build base then the sugar
What does the first step of purine synthesis use?
PRPP
What does the second step of purine synthesis produce?
IMP
What does IMP produce?
AMP and GMP
What are AMP and GMP used for?
They are used to create nucleoside triphosphates for RNA and DNA synthesis
What inhibits Purine biosynthesis?
AMP and GMP inhibit their production from IMP.
ADP and GDP inhibit the production of PRPP
What is uric acid and how is it excreted?
It is a product of purine degradation, gets excreted through urine.
What is gout?
The build up of uric acid crystals in the joints and kidneys
What causes gout?
A defect in the purine degredation pathway
There is an increase in PRPP synthetase activity which causes an over production of IMP
What is Lesch-Nyhan Syndrome?
HGPRT enzyme deficiency
-This enzyme is used to salvage hypoxanthine and guanine bases
Rare
Cuases neurologic symptoms including severe anxiety and self mutilation
X-linked recessive mutation- 2X more likely in women
What is Adenosine Deaminase Deficiency?
It is caused by a defect in adenosine deaminase
It leads to severe combined immunodeficiency disease (SCID)
Only treatment is a bone marrow transplant
How is ADA being treated with gene therapy?
By using Human Stem cells
What are the characteristics of Pyrimidine metabolism?
All atoms are derived from aspartate or carbamoyl phosphate
It is a 6 step process
What is the main product of pyrimidine biosynthesis?
UMP
What does UTP make?
CTP
What is the allosteric regulation of Pyrimidine biosynthesis?
Regulated by feedback inhibition and allosteric activation
What are the positive allosteric activators of Pyrimidine biosynthesis?
PRPP and ATP
What are the negative allosteric regulators of Pyrimidine biosynthesis?
CTP, UTP, UDP
What are the products of pyrimidine degradation?
NH4+, HCO3-, B-alanine, B-aminobutyrate
What is the purpose of 5-Fluorouracil?
It’s a potent anti-cancer medication that inhibits thymidylate synthesis (dUMP->dTMP)
Patients must be screened for dihydropyrimidine dehydrogenase activity
What are deoxyribonucleotides derived from?
They are derived from ribonucleotides in a single reaction by ribonucleotide reductase
What does ribonucleotide reducase require?
2 e- from NADPH
What is the net equation for deoxyribonucleotide metabolism?
NADPH+ H+ +nucleoside 5’-diphosphate—> H20 + deoxynucleoside 5’-diphosphate + NADP+
How is ribonucleotide reductase regulated?
It has substrate specificity and overall activity
Allosteric effector binding regulates activity
What does thymidylate synthase do?
Converts dUMP to dTMP by adding a methyl group
What are the inhibitors of Thymidylate Synthesis?
Uracil-based compounds can be used to block activity of thymidylate synthesis
This can act as potent anticancer medications
Raltitrexed
Methotrexate
What are anti-cancer drug “cocktails”?
Mixture of drugs where each drug blocks a specific process in order to maximize chances of killing the cancer cells before drug resistance begins
What is a gene that can mutate to form cancer?
ONCA genes
What are some characteristics of DNA replication?
It occurs at a high rate in order to copy the entire genome
It is semiconservative
—> original duplex DNA template is separated into two strands
—>Each daughter molecule contains one strand of original template
—> discovered by meselson and stahl
Is DNA replication unidirectional or bidirectional?
Bidirectional
Two replication forks
What happens after the replication fork is formed?
- Double stranded DNA is converted into single stranded DNA
- RNA primer is added
- RNA primer is extended
What is the replisome?
The complete complex of proteins and enzymes required to replicated DNA
What are okazaki fragments?
fragments that are synthesized while the other strand is synthesized continuously
Continual strand is know as the leading strand
Discontinuous strand containing okazaki fragments is known as the lagging strand
What is DNA Polymerase?
Enzymes responsible for the bulk of DNA synthesis
There is Mg+ to cofactor for this reaction
Primers are necessary
What is the direction of DNA synthesis?
5’—–> 3’
What is important about the active site of DNA polymerase?
It facilitates complimentary base pairing because of the fit
What is the Klenow fragment?
Cleavage of DNA polymerase I results in two fragments:
5’—–>3’ exonuclease activity
Klenow fragment
What is Reverse Transcriptase?
Enzyme used to convert RNA to DNA
Used in HIV replication
highly prone to error
no proof reading function
What is DNA helicase?
Separates the double stranded DNA
Specific to the reaction they catalyze
Involved in DNA repair and replication
ATP-dependent
What is the Trombone model?
Coordinated DNA synthesis on the leading and lagging strand templates by two POL III core complexes is mediated by the clamp loader complex.
Pol III core on the lagging strand template alternates between bound and unbound forms as each Okazaki fragment is made
How does prokaryotic and Eukaryotic DNA replication differ?
They use different DNA polymerases
What oriC?
The spot where DNA is separated to initiate replication in prokaryotes
Several steps involve ATP binding or hydrolysis
What are termination proteins?
Makes up the termination region, where DNA replications ends. Halfway around the genome
How is DNA replication regulated?
Cell cycle timing
What is telomerase?
Adds telomeric DNA sequences to the ends of chromosomal DNA
limited to undifferentiated embryonic stem cells, male germ cells, and activated lymphocytes in human
Shortening is a major factor of aging
What are mutations?
Permanent change in DNA sequence
can affect gene function
can alter protein-coding sequence
What are somatic mutations?
Not genetically inherited
result in decreased cell viability
can alter genes that are regulators of cell division
What is the Ames test?
Biochemical test to determine if a substance is mutagenic
What are the different types of DNA damage?
Spontaneous deamination of C to U
-improper complimentary base pairing
-generates abasic site
Environmental factors
-UV radiation
-Can result in stalled replication form and double strand break
DNA alkylation
What is the Cytosine deamination reaction?
Water converts NH group to ketone (cytosine to uracil)
What is autophagy?
Repair to the cell, engulfs damaged cell products and takes them to the lysosome to be broken down
-non aggregated proteins
-damaged mitochondria
-big molecules
How does DNA damage affect protein coding?
3 nucleotide bases in DNA specify an amino acid codon in RNA
Mutations:
Missense
nonsense
Silent
What are the mechanisms for DNA repair?
Mismatch repair
Done by mismatch repair proteins MutS and MutL
What is the base excision repair mechanism?
It is responsible for removal and replacement of individual bases that are damaged by various chemical reactions, including damage by ROS
What is short-patch repair?
Involves removal and replacement of single nucleotide catalyzed DNA polymerase and DNA lyase
What is long-patch repair?
Involves the synthesis of up to 10 or more nucleotides using a strand displacement mechanism
FEN removes the displaced strand, leaving behind a single strand nick that is sealed by DNA ligase
What is Nucleotide Excision Repair?
Used for large lesions that distort the helical nature of DNA
What are the two methods of double-strand breaks?
Homologous recombination
Nonhomologous end joining- does not require DNA template strand
What is DNA recombination?
Homologous recombination occurs during meiosis
double strand DNA breaks are required
promotes diversity!
What is the Holliday junction?
Region of a quadruplex DNA where 4 different DNA strands come together
-Branch migration
-are resolved by the enzyme resolvase to separate the joined chromosomes
What is the lysogenic cycle?
They cause the cell to stay in tact after a bacterial infection
