Lecture Exam 3 Flashcards
What is fatty acid synthase? In the mammalian enzyme, how many active sites does the enzyme have?
-Fatty Acid Synthase: catalyzes assembly of long carbon chains of fatty acids in the cytosol through a repeating four-step sequence
-Seven active sites are in separate domains within a single multifunctional polypeptide chain
What is the general process of fatty acid synthesis? What role does malonyl play?
Addition of two carbons to a growing fatty acyl chain: a four-step sequence.
Each malonyl group and acetyl (or longer acyl) group is activated by a thioester that links it to fatty acid synthase, a multienzyme system.
Condensation of an activated acyl group (an acetyl group from acetyl-CoA is the first acyl group) and two carbons derived from malonyl-CoA, with elimination of CO2 from the malonyl group, extends the acyl chain by two carbons. The mechanism of the first step of this reaction is given to illustrate the role of decarboxylation in facilitating condensation.
The β-keto product of the condensation is then reduced in three more steps nearly identical to the reactions of β oxidation, but in the reverse sequence: the β-keto group is reduced to an alcohol
Elimination of H2O (dehydration) creates a double bond
The double bond is reduced to form the corresponding saturated fatty acyl group
What do elongases and desaturases do?
-Fatty Acid Elongation Systems: lengthen palmitate to form long saturated fatty acids
-Fatty acyl-CoA Desaturase: catalyzes an oxidative reaction that introduces a double bond into a fatty acid chain; is a mixed-function oxidase
What is COX and what molecules does it produce?
-COX: prostaglandin H2 synthase catalyzes the formation of prostaglandin H2 (PGH2)
-COX-1: catalyzes the synthesis of prostaglandins that regulate gastric mucin secretion
-COX-2: catalyzes the synthesis of prostaglandins that mediate pain, inflammation, and fever
What is the general process of triacylglycerol synthesis?
Acyl transferase catalyzes the acylation of the 2 free hydroxyl groups of glycerol 3-phosphate by two molecules of fatty acyl-CoA to yield diacylglycerol 3-phosphate (phosphatidic acid)
Phosphatidic acid phosphatase hydrolyzes phosphatidic acid to form 1,2-diacylglycerol
1,2-diacylglycerol is converted to triacylglycerol by transesterification with a third fatty acyl-CoA
Promoted by insulin
What is the general process of phospholipid synthesis?
Begins with phosphatidic acid or diacylglycerols
Polar head group is attached through a phosphodiester bond (to CDP-diacylglycerol or to hydroxyl of the head group)
What role does HMG-CoA play in cholesterol synthesis? What drugs target this step
-HMG-CoA: is reduced by HMG-CoA reductase to form mevalonate; this is the major regulation point for cholesterol synthesis
-Statins: drug class used to treat patients with elevated serum cholesterol
How is cholesterol synthesis and metabolism regulated?
Covalent modification of HMG-CoA reductase
Transcriptional regulation of HMG-CoA gene
Proteolytic degradation of HMG-CoA reductase
Activation of ACAT, which increases esterification for storage
Transcriptional regulation of the LDL receptor
Insulin and ACAT promote
Glucagon and oxysterol inhibit
How do HDL, LDL, VLDL/IDL, and chylomicrons work in transporting lipids? What are their roles?
-HDL: transports lipids using reverse cholesterol transport
-HDL picks up cholesterol from cholesterol-rich extrahepatic cells and returns it to the liver for unloading
-LDL: carries cholesterol to extrahepatic tissues and macrophages
-VLDL/IDL: lipoproteins that carry cholesterol esters or triacylglycerols from the liver to muscle and adipose tissue
How does cholesterol give rise to steroid hormones?
-Cholesterol undergoes side-chain cleavage in the mitochondria of steroidogenic tissues
-This reaction is catalyzed by mixed-function oxygenases that use NADPH, O2, and mitochondrial P-450
What is nitrogen fixation and nitrogen assimilation? What organisms accomplish this?
-Nitrogen fixation: the conversion of N2 to forms that can support life (NH3, NO2-, NO-)
-Nitrogen Assimilation: a two-step reductive process that bypasses atmospheric N2
-Only bacteria and archaea can fix atmospheric N2 (diazotrophs)
What is glutamine synthetase? What type of inhibition regulates this enzyme?
-There are 3 classes of glutamine synthetase
-GS1(found in bacteria): 12 identical subunits
-GS2 (found in eukaryotes and some bacteria): 10 identical subunits
-GSIII (found in two bacterial species): double-ringed dodecamer of identical chains
-Glutamine synthetases are regulated allosterically, the products work together to provide cumulative feedback inhibition
-Covalent modification helps to increase sensitivity to the allosteric inhibitors
What are some key precursors to amino acid synthesis?
-Carbon skeleton precursors are derived from:
-glycolysis
-the citric acid cycle
-the pentose phosphate pathway
How do essential and nonessential amino acids differ?
Essential amino acids are required in the diet.
Nonessential amino acids are synthesized in the body.
What amino acids serve as a precursor to heme, histamine, and neurotransmitters?
-Heme: glycine
-Histamine: histidine
-Neurotransmitters: tyrosine, histidine, tryptophan
What does heme become when it is broken down?
-Heme becomes bilirubin, which is converted to bile pigments
What does heme become when it is broken down?
-Heme becomes bilirubin, which is converted to bile pigments
What amino acids make up glutathione?
-Derived from glutamate, cysteine, and glycine
What molecules serve as a precursor of purines?
-Glycine
What molecules serve as a precursor of pyrimidines?
Aspartic Acid
What do nucleotide kinases and ribonucleotide reductases do?
-Nucleoside Monophosphate Kinases: use ATP to form other nucleoside diphosphates
-Nucleoside dispohosphate kinases: convert nucleoside diphosphates to triphosphates
-Ribonucleotide Reductase: converts ribonucleotides to deoxyribonucleotides
What is gout and what causes it?
Gout is a disease of the joints caused by an elevated concentration of uric acid in the blood and tissues
How are nucleotide synthesis pathways targeted by cancer drugs?
Many chemotherapeutic agents target enzymes in nucleotide biosynthetic pathways.
Targets include thymidylate synthase and dihydrofolate reductase, enzymes that provide the only cellular pathway for thymine synthesis
How are neuronal and endocrine signaling different?
-Neuronal Signaling: nerve cells release neurotransmitters that act on nearby cells (distance may be small)
-Endocrine Signaling: hormones are carried by the bloodstream to nearby cells or other organs (distance may be great)
What are metabotropic receptors, ionotropic receptors, and nuclear receptors?
-Metabotropic: cell surface horome receptors that activate or inhibt a downstream enzyme
-Iontropic: those that open or close an ion channel in the plasma membrane, resulting in a change of Vm or ion concentration
-both are cell surface receptors
-Nuclear: steroid or thyroid hormone enters the cell; hromone-receptor complex acts in the nucleus
How do endocrine, paracrine, and autocrine signaling differ? Provide an example of each.
-Endocrine: released into the blood and carried to target cells throughout the body Ex: insulin and glucagon
-Paracrine: released into the extracellular space and diffuse to neighboring target cells Ex: eicosanoid hormones
-Autocrine: affect the same cell that releases them Ex: cancer
How does insulin get activated?
-Insulin is converted to active insulin by proteases when blood glucose is sufficiently elevated
What does the hypothalamus do?
-Hypothalmus: the coordination center of the endocrine system; receives and integrates messages from the CNS; produces releasing factors
What is the difference between top-down and bottom-up signaling?
-Top-Down: at each level of a hormonal cascade, feedback inhibition of earlier steps is possible
-Bottom-Up: some hormones are produced in the digestive tract, muscle, and adipose tissue and communicate the current metabolic state to the hypothalamus
What are some roles of the liver in metabolism?
-The liver processes fats, carbs, and proteins from diest; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea
-Central processing and distribution organ for nutrients; can adjust metabolism to meet changing circumstances
What is the difference between slow-twitch and fast-twitch muscle fibers?
-Slow-Twitch Muscle (red muscle): provides relatively low tension but is highly resistant to fatigue; processes ATP by oxidative phosphorylation; very rich in mitochondria; served by dense networks of blood vessels which bring oxygen
-Fast-Twitch Muscle (white muscle): can develop greater tension and do so faster, but is quicker to fatigue; has fewer mitochondria than red muscle; is less well-supplied with blood vessels; uses ATP faster than it can replace it
What is creatine phosphate and what role does it play in the maintenance of ATP levels in muscles?
-Creatine Phosphate: rapidly regenerates ATP from ADP
-Creatine Phosphare buffers ATP concentration by creating a reservoir during continued respiration
What is the Cori cycle and what does it do?
-Cori Cycle: the movement of lactate from the muscle to the liver for conversion to glucose via gluconeogeneis
-during recovery, lactate is transported to the liver and converted to glucose by gluconeogenesis
-glucose is released to the blood and returned to the muscles to replenish their glycogen stores
What are the key cell types and components of blood?
-Erythrocytes (RBCs): filled with hemoglobin and specialized for carrying O2 and CO2
-Leukocytes (WBCs): central to the immune system to defend against infections; include lymphocytes
-Platelets (cell fragments): help to mediate blood clotting
-Blood Plasma: the liquid portion of blood; 90% water and 10% solutes
-Plasma Proteins: immunoglobine, serum albumin, apolipoproteins, transferrin, and blood clotting proteins; make up more than 70% of the plasma solids
What processes are regulated based upon dietary intake of food (well-fed vs. fasting)?
Well-Fed
Increase in glucose intake promotes glycolysis, glycogenesis, fatty synthesis
Fasting
Decrease in glucose intake promotes glucagon secretion and converts fatty acids to ketone bodies
What are some examples of dietary hormones in regulating feeding?
Leptin = an adipokine produced by adipose tissue that regulates feeding behavior and energy expenditure to maintain adequate reserves of fat; an adipokine released when adipose tissue is well-filled with triacylglycerols
Acts in the brain to inhibit feeding
Production and release increases with number and size of adipocytes
Neuropeptide Y (NPY) = a hormone produced in the hypothalamus and in the adrenal glands
Promotes feeding and reduces nonessential energy expenditure
Adipokines = peptide hormones produced in adipose tissue that signal the adequacy of fat reserves
Adiponectin = an adipokine released when adipose tissue is depleted of fat reserves
Acts in the brain to stimulate feeding
Ghrelin = produced in the gastrointestinal tract when the stomach is empty
Acts in the hypothalamus to stimulate feeding
What is a probiotic? What is a prebiotic? What are PPARs?
Weight reduction might be accomplished by adding to the gut either:
Probiotics (microbial species that disfavor adipogenesis)
Prebiotics (nutrients that favor the dominance of probiotic microbes)
-peroxisome proliferator-activated receptors (PPARs) =
family of ligand-activated transcription factors
– respond to changes in dietary lipid by altering the
expression of genes involved in fat and carbohydrate
metabolism
What are some differences between type I and type II diabetes?
Type I diabetes: stems from an autoimmune destruction of pancreatic B cells, resulting in the inability to produce sufficient insulin
Begins early in life
Responds to insulin injection
Caused by genetics
Type II Diabetes: group of diseases in which the regulatory activity of insulin is disordered
Slower to develop and typically in obese adults
Responds to insulin injection
Caused by lifestyle choices
