What is the difference between a Fisher projection and a Haworth projection of a monosaccharide?
• Fisher projections are the linear versions of carbohydrates. • Haworth projections are the cyclical versions of carbohydrates.
How do you choose between a pyranose and a furanose ring when drawing a cyclic sugar?
Choose the ring size as either pyranose or furanose based on which ring (six- or five-membered) the sugar forms.
Where is the anomeric carbon located when converting a Fisher to a Haworth projection?
The carbonyl carbon moves one position clockwise from the ring oxygen and becomes the anomeric carbon in the Haworth projection.
How is the orientation of the former carbonyl (=O) shown in the cyclic form for alpha vs beta anomers?
The former =O becomes OH at the anomeric carbon: UP = β and DOWN = α.
Where does carbon numbering start in a monosaccharide aldose?
Carbon numbering starts at the carbonyl end; in open-chain aldoses the carbonyl carbon is C1.
How are carbons numbered for ring sugar positions after placing the anomeric carbon?
For ring naming, number carbons clockwise after placing the anomeric carbon.
What are constitutional isomers and what is a tautomer?
• Constitutional isomers change atom connectivity. • Tautomers are constitutional isomers where the order or position of hydrogens changes.
What defines configurational isomers, enantiomers, and diastereomers?
• Configurational isomers differ at chiral carbons. • Enantiomers are mirror images at all chiral centers. • Diastereomers have multiple chiral centers and are not mirror images at all centers.
How do anomers and epimers differ?
• Anomers differ only at the anomeric carbon (α vs β). • Epimers differ at any single carbon other than the anomeric carbon.
What are conformational isomers?
Conformational isomers arise from reversible rotation around single bonds.
Why is transport of glucose into the cell the initial step in glucose metabolism?
Because glucose is polar and cannot cross the cell membrane without transport.
Where is GLUT1 highly expressed and what is its affinity for glucose?
Highly expressed in RBCs and brain; GLUT1 has high affinity for glucose.
Which tissues primarily use GLUT2 and what is its affinity?
Liver and pancreas primarily use GLUT2; GLUT2 has low affinity for glucose.
Which GLUT isoform is the main neuronal glucose transporter and what is its affinity?
GLUT3 is the main neuronal transporter; it has high affinity for glucose.
Where is GLUT4 found and how is it regulated?
GLUT4 is in skeletal muscle, adipose tissue, and heart; it is sequestered in vesicles and inserted into the membrane in response to insulin.
What is the overall stoichiometry of glycolysis for one glucose molecule?
One glucose is metabolized to two pyruvate and generates two ATP.
What enzyme catalyzes the phosphorylation of glucose in most tissues?
Hexokinase catalyzes glucose → glucose-6-phosphate in most tissues.
Which enzyme performs the glucose → glucose-6-phosphate step in the liver?
Glucokinase performs glucose → glucose-6-phosphate in the liver.
Which enzyme converts glucose-6-phosphate to fructose-6-phosphate in glycolysis?
Phosphoglucoisomerase converts glucose-6-phosphate → fructose-6-phosphate.
What is the rate-limiting enzyme of glycolysis and its reaction?
Phosphofructokinase (PFK) is rate-limiting and converts fructose-6-phosphate → fructose-1,6-bisphosphate.
Name the regular essential monosaccharides listed.
Which monosaccharide is described as the 'oddball' essential monosaccharide?
L-fucose
Which amino sugars are listed as essential?
How do glycoproteins differ from proteoglycans in protein-to-sugar weight ratio?
Glycoproteins have more protein than sugar by weight; proteoglycans have more sugar than protein by weight.
What structural feature characterizes proteoglycans' carbohydrate component?
Proteoglycans have repeating disaccharide units called glycosaminoglycans (GAGs) that are linear and unbranched.
What distinguishes mucins from proteoglycans in carbohydrate structure and function?
Mucins have more complex, branched sugar patterns (not simple disaccharide repeats) and function in lubrication for protection and hydration.
Which enzymes convert fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP)?
Which glycolytic stage generates NADH and ATP and name key enzymes involved?
How does fructose metabolism in liver enter glycolysis differently from glucose?
Fructose metabolism in liver bypasses the PFK-1 step; fructokinase and triose kinase generate intermediates that feed glycolysis in an unregulated fashion
Why can excess dietary fructose contribute to fatty liver and obesity?
Excess fructose-derived GAP and DHAP are converted to pyruvate and acetyl-CoA and then to fatty acids and triacylglycerols, promoting fatty liver and obesity
How does galactose enter the glycolytic pathway?
Galactose is converted via the galactose pathway to glucose-1-phosphate, then to glucose-6-phosphate for entry into glycolysis
What are the three irreversible phosphorylation checkpoints in glycolysis?
Which enzyme is the rate-limiting step of glycolysis and what reaction does it catalyze?
PFK-1 is the rate-limiting enzyme; it catalyzes conversion of fructose-6-phosphate to fructose-1,6-bisphosphate
List major allosteric regulators of PFK-1.
How do insulin and glucagon affect PFK-1 activity via F2,6BP?
What regulates pyruvate kinase activity?
How does hepatic glycolytic regulation differ from muscle?
What is the defect and consequence of Fanconi-Bickel syndrome?
Mutation in GLUT2 causing inability of cells to take up glucose, fructose, and galactose
What causes Tarui disease and what are key clinical features?
Tarui disease is due to PFK-1 deficiency; presents with exercise-induced muscle cramps and weakness, hemolytic anemia, high bilirubin, and jaundice
Why is excessive fructose consumption linked to fatty liver and insulin resistance?
Because fructose bypasses the main regulatory step in glycolysis, leading to metabolic disturbances such as fatty liver, insulin insensitivity, obesity, and type 2 diabetes.
What enzyme deficiency causes classic (type I) galactosemia?
Deficiency of galactose-1-phosphate uridyltransferase (GALT).
Name clinical consequences of classic galactosemia from GALT deficiency.
Define gluconeogenesis and where it occurs.
Gluconeogenesis is synthesis of glucose from non-carbohydrate precursors and occurs in liver and kidney.
Why is gluconeogenesis not simply the reverse of glycolysis?
Because it bypasses the three irreversible glycolytic steps using four different enzymes not present in glycolysis.
Which four enzymes bypass the irreversible steps of glycolysis in gluconeogenesis?
Outline the main substrate flow from pyruvate to free glucose in gluconeogenesis.
Pyruvate → oxaloacetate (in mitochondria) → PEP → ... → fructose-1,6-bisphosphate → fructose-6-phosphate → glucose-6-phosphate → free glucose.
Why is maintaining blood glucose important physiologically?
Because the brain depends on glucose as its primary fuel and red blood cells use glucose as their only fuel.
When is gluconeogenesis especially important during fasting?
Gluconeogenesis is especially important during longer fasting or starvation because direct glucose reserves meet needs for only about a day.
What are the major precursors for gluconeogenesis?
What is the Cori cycle?
The Cori cycle links lactate from anaerobic glycolysis in red blood cells and exercising muscle to gluconeogenesis in the liver, regenerating glucose.
Which enzyme is the rate-limiting step of gluconeogenesis?
Fructose-1,6-bisphosphatase is the rate-limiting enzyme of gluconeogenesis.
List key features of pyruvate carboxylase.
Mitochondrial enzyme; activated allosterically by acetyl-CoA; uses ATP and biotin; increased by cortisol via transcriptional induction.
State two regulatory facts about PEPCK.
PEPCK uses GTP and is transcriptionally activated by cortisol, glucagon, and thyroxine.
How is fructose-1,6-bisphosphatase regulated?
Activated by cortisol and citrate; inhibited by AMP and fructose-2,6-bisphosphate (F2,6BP).
Where is glucose-6-phosphatase located and in which tissues is it present?
Glucose-6-phosphatase is located in the endoplasmic reticulum lumen and is present in liver, kidneys, small intestine, and pancreas.
How does cellular energy charge affect glycolysis and gluconeogenesis?
Energy charge determines which pathway is most active; glycolysis and gluconeogenesis are reciprocally regulated.
What is the basic structural composition of glycogen?
Which glycosidic bonds form the linear chains and branch points in glycogen?
What are the ends of a glycogen molecule and what protein primes its synthesis?
Where is glycogen primarily stored and what is its role in liver versus muscle?
What is the first step (trapping and activation) of glycogen synthesis and which enzymes are involved?
Which enzyme performs elongation during glycogen synthesis and what is its role?
Which enzyme creates branch points in glycogen and what bond does it form?
What is the rate-limiting enzyme of glycogenolysis and what cofactor does it use?
Which enzyme converts glucose-1-phosphate to glucose-6-phosphate during glycogen breakdown?
What is the role of the debranching enzyme in glycogenolysis?
How does biotin deficiency affect gluconeogenesis?
What enzyme deficiency causes Von Gierke disease (GSD Ia) and how does it affect glucose release?
What are the two key enzymes that control glycogen synthesis and degradation?
Name three shared regulatory mechanisms for glycogen synthase and glycogen phosphorylase.
How is liver glycogen phosphorylase regulated by glucose and AMP?
How is muscle glycogen phosphorylase regulated by AMP, ATP, and glucose-6-phosphate?
What is the reciprocal relationship between glycogen synthase and glycogen phosphorylase when one is activated?
Activation of one enzyme coincides with inhibition of the other (effects in opposite directions).
Which state favors glycogenesis and what are the hormonal and energetic conditions?
The fed state favors glycogenesis: blood glucose high, insulin high, cellular ATP high.
In the fed state, what are the phosphorylation states and activities of glycogen synthase and glycogen phosphorylase?
Which conditions favor glycogenolysis and which signals mediate it in liver and muscle?
Fasting (low glucose, high glucagon) and exercise (high Ca2+ and AMP in muscle) favor glycogenolysis.
When glycogen breakdown is favored, what are the phosphorylation states and activities of the two enzymes?
How does liver differ from muscle in handling glucose-6-phosphate after glycogenolysis?
How does insulin signaling promote glycogen synthesis at the molecular level?
Insulin activates PKB which activates PP1 and inactivates GSK3; PP1 dephosphorylates glycogen synthase (activating it) and dephosphorylates glycogen phosphorylase (inactivating it).
How do glucagon and epinephrine promote glycogen breakdown via second messengers?
They raise cAMP and activate PKA, which phosphorylates glycogen synthase (inactivating it), activates phosphorylase kinase, and promotes activation of glycogen phosphorylase, causing glycogen breakdown.
What is the primary defect and clinical consequence of GSD 0?
GSD 0 is glycogen synthase deficiency; patients cannot synthesize/store glycogen and are vulnerable to fasting hypoglycemia.
What enzyme is deficient in GSD Ia (Von Gierke disease) and name three clinical features?
Deficiency of glucose-6-phosphatase; features: marked fasting hypoglycemia, lactic acidosis, hepatomegaly.
What enzyme deficiency causes GSD II (Pompe disease)?
Acid maltase (lysosomal α-glucosidase) deficiency
What is the primary pathological consequence of Pompe disease (GSD II)?
Glycogen accumulates in lysosomes causing progressive muscle weakness and myopathy, including heart muscle
Which enzyme is deficient in GSD III (Cori disease)?
Debranching enzyme deficiency
How does glycogen structure change in Cori disease (GSD III)?
Glycogen has many short branches
What are two clinical features of GSD III (Cori disease)?
Which enzyme deficiency causes GSD IV (Andersen disease)?
Branching enzyme deficiency
How is glycogen structurally altered in Andersen disease (GSD IV)?
Glycogen has long chains with fewer branches
Name two major clinical consequences of Andersen disease (GSD IV).
Give an overview statement of the citric acid (TCA) cycle's role.
The TCA cycle is a biochemical hub that oxidizes carbon fuels to harvest high-energy electrons, is amphibolic, supplies biosynthetic precursors, and occurs inside mitochondria
What are the products from oxidation of a 2-carbon acetyl unit in the TCA cycle?
2 moles of CO2, 1 mole of GTP, and high-energy electrons as NADH and FADH2
Where are energy nutrients converted before entering the TCA cycle?
Energy nutrients are degraded to an acetyl-CoA pool, and acetyl-CoA enters the TCA cycle
How does oxidative phosphorylation relate to the TCA cycle?
Oxidative phosphorylation in mitochondria uses TCA-derived high-energy electrons to produce ATP
How does pyruvate enter mitochondria for PDH to act on it?
Pyruvate enters mitochondria through the mitochondrial pyruvate carrier
What reaction does the pyruvate dehydrogenase complex (PDC) catalyze?
Decarboxylation of pyruvate to form acetyl-CoA with production of CO2 and NADH
How many enzymes and coenzymes are required by the PDC?
The reaction requires 3 enzymes (E1, E2, E3) and 5 coenzymes: TPP, lipoic acid, FAD, CoA, and NAD+
What is the metabolic link function of PDH?
PDH links glycolysis to the citric acid cycle by converting pyruvate to acetyl-CoA
Name two regulatory mechanisms of PDH activity.
How do high acetyl-CoA and PDH products affect PDH regulation?
High acetyl-CoA directly inhibits E2, and PDH products increase phosphorylation (inactivating PDH)
Which molecules activate phosphatases that stimulate PDH during muscle contraction?
ADP and pyruvate activate phosphatases; Ca2+ stimulates phosphatases during muscle contraction
List the core enzymes of the citric acid cycle.
What reaction does citrate synthase catalyze in the TCA cycle?
Condensation of oxaloacetate with acetyl-CoA to form citrate
Which TCA enzyme is described as the rate-limiting step and how is it regulated?
Isocitrate dehydrogenase is the rate-limiting step; it is allosterically stimulated by ADP and inhibited by NADH
How is α-ketoglutarate dehydrogenase regulated?
It is inhibited by its products succinyl-CoA and NADH and is regulated similarly to PDH
Which two enzymes integrate the TCA cycle with other pathways?
What is the role of anaplerotic reactions in the citric acid cycle?
Anaplerotic reactions 'fill up' and replenish TCA cycle intermediates used for biosynthesis.
Name the two major anaplerotic reactions shown.
Which reaction forms oxaloacetate to replenish TCA intermediates?
Formation of oxaloacetate from pyruvate (pyruvate carboxylation).
List key structural features of mitochondria relevant to metabolism.
What makes the outer and inner mitochondrial membranes different?
Outer membrane is permeable due to porin/VDAC; inner membrane is impermeable, contains metabolite transporters, and is folded into cristae.
Which mitochondrial compartment contains the TCA cycle and fatty acid oxidation?
The mitochondrial matrix is the site of the TCA cycle and fatty acid oxidation.
What features describe mitochondrial genetics and inheritance?
Mitochondria are semi-autonomous with their own DNA, and human mitochondrial DNA is maternally inherited.
What are the three requirements for successful oxidative phosphorylation?
Briefly describe the flow of electrons and protons in oxidative phosphorylation.
High-energy electrons from NADH and FADH2 flow through ETC complexes, reduce O2 to water, three complexes pump protons to the intermembrane space, and protons return through ATP synthase to make ATP.
What is the function of Complex I in the electron transport chain?
Complex I (NADH-Q oxidoreductase) is the first entry point for electrons from NADH.
What distinguishes Complex II from other ETC complexes?
Complex II (succinate-Q reductase) connects the TCA cycle to OxPhos and does not pump protons.
What is the role of Complex III in the electron transport chain?
Complex III (Q-cytochrome c oxidoreductase) transfers electrons from QH2 to cytochrome c and contributes to proton translocation.
What is the role of Complex IV in the electron transport chain?
Complex IV (cytochrome c oxidase) transfers electrons from reduced cytochrome c to molecular oxygen and reduces it to water.
Name the two mobile electron carriers in the electron transport chain.
Where do electrons from NADH enter the mitochondrial electron-transport chain?
Electrons from NADH enter at Complex I, then pass to coenzyme Q, Complex III, cytochrome c, and Complex IV where O2 is the final acceptor.
Where do electrons from FADH2 enter the electron-transport chain?
Electrons from FADH2 enter through Complex II, pass to coenzyme Q, then through Complex III and Complex IV to O2.
Why does oxidation of FADH2 yield less ATP than NADH?
Because Complex II does not pump protons, oxidation of FADH2 contributes fewer pumped protons and thus less ATP synthesis.
What is the final electron acceptor in the mitochondrial electron-transport chain?
Molecular oxygen (O2) is the final electron acceptor at Complex IV.
What reactive oxygen species do mitochondria generate?
Mitochondria generate superoxide free radicals.
What damage can toxic oxygen derivatives and free radicals cause?
They can damage macromolecules and contribute to various pathologies.
What reaction does superoxide dismutase catalyze?
Superoxide dismutase converts superoxide to oxygen and hydrogen peroxide.
What reaction does catalase catalyze?
Catalase converts hydrogen peroxide to oxygen and water.
Name other antioxidant systems listed.
Other antioxidant systems include glutathione peroxidase, thioredoxin, vitamin E, and vitamin C.
State the chemiosmotic hypothesis in brief.
The electron-transport chain translocates protons across the inner membrane as electrons flow, generating a proton-motive force (∆pmf) used by ATP synthase to phosphorylate ADP.
What are the components of the proton-motive force (∆pmf)?
The proton-motive force is composed of a pH gradient (ΔpH) and a membrane potential (ΔΨ).
Why does disruption of the inner mitochondrial membrane prevent ATP synthesis?
The inner membrane is impermeable to H+ and OH−; if disrupted an Δpmf cannot be established, so ATP synthesis does not occur.
Describe the main structural sectors of ATP synthase (Complex V).
ATP synthase has an F0 membrane-embedded proton channel and an F1 sector protruding into the matrix containing catalytic domains.
What is the subunit composition of the F1 sector and which subunits are catalytic?
The F1 sector contains a3β3γδε; α and β alternate in a hexameric ring, and only the β subunits are catalytically active.
How many protons are approximately required to synthesize one ATP via ATP synthase?
About 3+1 H+ passage is required per ATP synthesized.
Besides catalysis, what structural role do ATP synthase oligomers have?
ATP synthase molecules form dimers and oligomers that help maintain cristae curvature.
What problem do shuttle systems solve for mitochondrial metabolism?
Reduced NADH cannot cross the mitochondrial membrane, so shuttle systems transfer reducing equivalents into mitochondria.
Name the two shuttle systems that move high-energy reducing equivalents into mitochondria.
How do ATP levels affect cellular respiration?
Cellular respiration is regulated by ATP levels; electron flow through the ETC occurs only when ADP is phosphorylated to ATP.
What is 'respiratory control' (acceptor control)?
Regulation of electron transport by ADP levels, where ADP availability controls ETC activity.
What happens to proton pumping and ATP synthesis when electron transport is inhibited?
Inhibition of electron transport decreases proton pumping, lowers the proton gradient, and inhibits ATP synthesis.
What is the mechanism of action of oligomycin on mitochondria?
Oligomycin inhibits ATP synthase (Complex V) by disrupting proton transport through its channel.
How do inhibitors that block electron transport affect ATP synthesis?
They decrease proton pumping and the H+ gradient, which leads to inhibition of ATP synthesis.
What is the difference between blocking electron flow and blocking Complex V in terms of respiration?
Targeting different ETC components either directly blocks electron flow (upstream) or blocks ATP synthesis at Complex V while electron flow may continue.
How does uncoupling affect ATP production and heat generation?
In uncoupling, protons re-enter without ATP synthesis; TCA cycle and electron transfer accelerate and energy is released as heat instead of ATP.
What role does UCP1 (thermogenin) in brown adipose tissue play?
UCP1 transfers protons from the cytoplasm to the matrix, converting proton-motive energy into heat rather than ATP.
Where does the Pentose Phosphate Pathway (PPP) branch from in carbohydrate metabolism?
The PPP branches from glucose-6-phosphate, linking it to glycogenesis/glycogenolysis, glycolysis/gluconeogenesis, and the PPP.
Which glycolytic intermediates are interconverted with PPP sugars in the nonoxidative phase?
Why is NADPH needed in cells?
NADPH is required for synthesis of monomers and for cellular reducing power.
What maintains the reduced glutathione (GSH) pool in healthy cells?
Regeneration of GSH using NADPH, maintaining a GSH:GSSG ratio of about \(500:1\).
What happens to cells when NADPH production is insufficient?
Cells cannot maintain redox homeostasis well and become vulnerable to oxidative damage.
Name a clinical condition resulting from impaired NADPH production in red blood cells.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which can cause acute hemolysis, chronic hemolytic anemia, and neonatal jaundice.
What is the rate-limiting enzyme of the oxidative phase of the Pentose Phosphate Pathway?
Glucose-6-phosphate dehydrogenase (G6PD).
What reaction does glucose-6-phosphate dehydrogenase catalyze?
Oxidizes glucose-6-phosphate to a lactone and reduces NADP+ to NADPH.
Which oligomeric forms of G6PD are active or inactive?
Active forms are dimer and tetramer; the monomer is inactive.
List activators of G6PD activity mentioned in the notes.
List inhibitors of G6PD activity mentioned in the notes.
What are the three reactions of the oxidative phase of the Pentose Phosphate Pathway?
What is the role of the nonoxidative phase of the Pentose Phosphate Pathway?
It shuffles carbons: converts ribulose-5-phosphate to ribose-5-phosphate and xylulose-5-phosphate and transfers 2- and 3-carbon units via transketolase and transaldolase.
How can the Pentose Phosphate Pathway be adjusted to meet different cellular needs?
What are the structural features of a fatty acid?
A fatty acid consists of a hydrocarbon chain plus a carboxyl group and is the primary hydrophobic determinant in lipids.
Why are fatty acids and lipids described as amphipathic?
Because they contain both a hydrophobic part (hydrocarbon) and a hydrophilic part (carboxyl group).
How do saturated and unsaturated fatty acids differ structurally and in melting point?
Saturated fatty acids have no C=C bonds, are more linear, and have higher melting points; unsaturated fatty acids contain cis/trans double bonds, are bent, and generally have lower melting points.
What does the fatty acid notation '18:2' mean?
Give common names for these fatty acids: 18:0, 18:1, 18:2, 18:3.
Which two omega fatty acids cannot be synthesized by humans?
Are ALA and LA efficiently converted to EPA, DHA, and arachidonic acid?
List three important roles of omega fatty acids.
According to the Fluid Mosaic Model, what are membrane lipids described as?
What are the majority lipid components of cell membranes?
What primarily determines membrane rigidity in humans?
What roles do glycosphingolipids play?
What is the composition of triacylglycerols?
What is Phase I of fatty acid synthesis?
What reaction defines Phase II of fatty acid synthesis and which enzyme catalyzes it?
What is Phase III of fatty acid synthesis?
Which enzyme is the rate-limiting enzyme in fatty acid synthesis?
What is the longest fatty acid chain produced by fatty acid synthase?
Palmitate (C16)
Where does elongation of fatty acids beyond C16 occur and what substrates are used?
Elongation occurs on the endoplasmic reticulum by fatty acid elongase using malonyl-CoA and NADPH.
Which enzymes catalyze desaturation of fatty acids in humans?
Desaturation is catalyzed in the smooth ER by NADH-cytochrome b5 reductase, cytochrome b5, and a desaturase.
At which carbon positions can humans introduce double bonds in fatty acids?
Humans can introduce double bonds only at Δ4, Δ5, Δ6, and Δ9 (A4, A5, A6, and A9).
Why are some fatty acids essential in the human diet?
Double bonds beyond carbon 9/10 cannot be synthesized by humans, so those fatty acids must come from the diet.
Which enzymes are the main regulatory targets in fatty acid synthesis?
The main targets are ATP citrate lyase, acetyl-CoA carboxylase (ACC), and fatty acid synthase.
What is the rate-limiting enzyme of fatty acid synthesis?
Acetyl-CoA carboxylase (ACC)
Which ACC oligomeric state is active and which is inactive?
The polymer of ACC is active; the monomer/dimer is inactive.
Name two activators of ACC.
Name inhibitors of ACC and the pathways that mediate inhibition.
How does diet affect gene expression of the fatty acid synthesis pathway?
A high-carbohydrate/low-fat diet up-regulates gene expression of the pathway.
What is the backbone molecule for triacylglycerol (TAG) synthesis?
Glycerol-3-phosphate
List the sequential intermediates in TAG synthesis from glycerol-3-phosphate.
How do liver and adipocytes differ in sources used for TAG synthesis?
In liver, glucose and glycerol provide glycerol-3-phosphate and newly synthesized FAs form TAGs for VLDL. In adipocytes, FAs from chylomicrons and VLDL are added to glycerol-3-phosphate for storage.
Which hormones promote TAG synthesis in hepatocytes?
TAG synthesis in hepatocytes is promoted by excess carbohydrates (metabolic state), not a specific hormone listed.
Which hormones promote breakdown of stored triacylglycerols (lipolysis)?
Name the three major lipases involved in triacylglycerol breakdown.
How are fatty acids transported in blood after release from adipose tissue?
Short-chain fatty acids are soluble in blood; long-chain fatty acids are transported bound to albumin.
What is Phase I of fatty acid breakdown?
Activation and transport of fatty acids to the mitochondrial matrix.
Which enzyme activates long-chain fatty acids on the outer mitochondrial membrane?
Fatty acyl-CoA synthetase
Name the transport steps and proteins that move fatty acids into the mitochondrial matrix.
List the four enzymatic steps of ß-oxidation in mitochondria.
What are the main products of ß-oxidation?
Which enzyme is the rate-limiting step in fatty acid degradation?
Carnitine palmitoyltransferase I (CPT-I)
How does malonyl-CoA affect fatty acid breakdown?
Malonyl-CoA inhibits CPT-I, preventing fatty acid degradation.
How is hormone-sensitive lipase (HSL) regulated by hormones?
HSL is activated by PKA-mediated phosphorylation (glucagon/epinephrine) and inhibited by insulin via PP1-mediated dephosphorylation.
Name the three main ketone bodies.
Where are ketone bodies produced?
Ketone bodies are produced only in liver mitochondria.
Why does ketone body formation increase during fasting?
Low carbohydrate availability lowers oxaloacetate, so excess acetyl-CoA from ß-oxidation condenses to form ketone bodies.
How does diabetic ketoacidosis develop in terms of hormone ratio and metabolism?
An increased glucagon/insulin ratio with impaired carbohydrate metabolism favors fatty acid breakdown, increasing hepatic acetyl-CoA and ketone formation.
Which ketone bodies lower blood pH and cause acidosis?
Acetoacetate and ß-hydroxybutyrate are strong acids that lower blood pH and cause acidosis.
What causes the fruity breath odor in uncontrolled diabetes?
Volatile acetone is exhaled in breath and gives the fruity odor.
What is the difference between a Fisher projection and a Haworth projection of a monosaccharide?
• Fisher projections are the linear versions of carbohydrates. • Haworth projections are the cyclical versions of carbohydrates.
How do you choose between a pyranose and a furanose ring when drawing a cyclic sugar?
Choose the ring size as either pyranose or furanose based on which ring (six- or five-membered) the sugar forms.
Where is the anomeric carbon located when converting a Fisher to a Haworth projection?
The carbonyl carbon moves one position clockwise from the ring oxygen and becomes the anomeric carbon in the Haworth projection.
How is the orientation of the former carbonyl (=O) shown in the cyclic form for alpha vs beta anomers?
The former =O becomes OH at the anomeric carbon: UP = β and DOWN = α.
Where does carbon numbering start in a monosaccharide aldose?
Carbon numbering starts at the carbonyl end; in open-chain aldoses the carbonyl carbon is C1.
How are carbons numbered for ring sugar positions after placing the anomeric carbon?
For ring naming, number carbons clockwise after placing the anomeric carbon.
What are constitutional isomers and what is a tautomer?
• Constitutional isomers change atom connectivity. • Tautomers are constitutional isomers where the order or position of hydrogens changes.
What defines configurational isomers, enantiomers, and diastereomers?
• Configurational isomers differ at chiral carbons. • Enantiomers are mirror images at all chiral centers. • Diastereomers have multiple chiral centers and are not mirror images at all centers.
How do anomers and epimers differ?
• Anomers differ only at the anomeric carbon (α vs β). • Epimers differ at any single carbon other than the anomeric carbon.
What are conformational isomers?
Conformational isomers arise from reversible rotation around single bonds.
Why is transport of glucose into the cell the initial step in glucose metabolism?
Because glucose is polar and cannot cross the cell membrane without transport.
Where is GLUT1 highly expressed and what is its affinity for glucose?
Highly expressed in RBCs and brain; GLUT1 has high affinity for glucose.
Which tissues primarily use GLUT2 and what is its affinity?
Liver and pancreas primarily use GLUT2; GLUT2 has low affinity for glucose.
Which GLUT isoform is the main neuronal glucose transporter and what is its affinity?
GLUT3 is the main neuronal transporter; it has high affinity for glucose.
Where is GLUT4 found and how is it regulated?
GLUT4 is in skeletal muscle, adipose tissue, and heart; it is sequestered in vesicles and inserted into the membrane in response to insulin.
What is the overall stoichiometry of glycolysis for one glucose molecule?
One glucose is metabolized to two pyruvate and generates two ATP.
What enzyme catalyzes the phosphorylation of glucose in most tissues?
Hexokinase catalyzes glucose → glucose-6-phosphate in most tissues.
Which enzyme performs the glucose → glucose-6-phosphate step in the liver?
Glucokinase performs glucose → glucose-6-phosphate in the liver.
Which enzyme converts glucose-6-phosphate to fructose-6-phosphate in glycolysis?
Phosphoglucoisomerase converts glucose-6-phosphate → fructose-6-phosphate.
What is the rate-limiting enzyme of glycolysis and its reaction?
Phosphofructokinase (PFK) is rate-limiting and converts fructose-6-phosphate → fructose-1,6-bisphosphate.
How do glycoproteins differ from proteoglycans in protein-to-sugar weight ratio?
Glycoproteins have more protein than sugar by weight; proteoglycans have more sugar than protein by weight.
What structural feature characterizes proteoglycans' carbohydrate component?
Proteoglycans have repeating disaccharide units called glycosaminoglycans (GAGs) that are linear and unbranched.
What distinguishes mucins from proteoglycans in carbohydrate structure and function?
Mucins have more complex, branched sugar patterns (not simple disaccharide repeats) and function in lubrication for protection and hydration.
Which enzymes convert fructose-1,6-bisphosphate into glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP)?
Which glycolytic stage generates NADH and ATP and name key enzymes involved?
How does fructose metabolism in liver enter glycolysis differently from glucose?
Fructose metabolism in liver bypasses the PFK-1 step; fructokinase and triose kinase generate intermediates that feed glycolysis in an unregulated fashion
Why can excess dietary fructose contribute to fatty liver and obesity?
Excess fructose-derived GAP and DHAP are converted to pyruvate and acetyl-CoA and then to fatty acids and triacylglycerols, promoting fatty liver and obesity
How does galactose enter the glycolytic pathway?
Galactose is converted via the galactose pathway to glucose-1-phosphate, then to glucose-6-phosphate for entry into glycolysis
What are the three irreversible phosphorylation checkpoints in glycolysis?
Which enzyme is the rate-limiting step of glycolysis and what reaction does it catalyze?
PFK-1 is the rate-limiting enzyme; it catalyzes conversion of fructose-6-phosphate to fructose-1,6-bisphosphate
List major allosteric regulators of PFK-1.
How do insulin and glucagon affect PFK-1 activity via F2,6BP?
What regulates pyruvate kinase activity?
How does hepatic glycolytic regulation differ from muscle?
What is the defect and consequence of Fanconi-Bickel syndrome?
Mutation in GLUT2 causing inability of cells to take up glucose, fructose, and galactose
What causes Tarui disease and what are key clinical features?
Tarui disease is due to PFK-1 deficiency; presents with exercise-induced muscle cramps and weakness, hemolytic anemia, high bilirubin, and jaundice
Why is excessive fructose consumption linked to fatty liver and insulin resistance?
Because fructose bypasses the main regulatory step in glycolysis, leading to metabolic disturbances such as fatty liver, insulin insensitivity, obesity, and type 2 diabetes.
What enzyme deficiency causes classic (type I) galactosemia?
Deficiency of galactose-1-phosphate uridyltransferase (GALT).
Name clinical consequences of classic galactosemia from GALT deficiency.
Define gluconeogenesis and where it occurs.
Gluconeogenesis is synthesis of glucose from non-carbohydrate precursors and occurs in liver and kidney.
Why is gluconeogenesis not simply the reverse of glycolysis?
Because it bypasses the three irreversible glycolytic steps using four different enzymes not present in glycolysis.
Which four enzymes bypass the irreversible steps of glycolysis in gluconeogenesis?
Outline the main substrate flow from pyruvate to free glucose in gluconeogenesis.
Pyruvate → oxaloacetate (in mitochondria) → PEP → ... → fructose-1,6-bisphosphate → fructose-6-phosphate → glucose-6-phosphate → free glucose.
Why is maintaining blood glucose important physiologically?
Because the brain depends on glucose as its primary fuel and red blood cells use glucose as their only fuel.
When is gluconeogenesis especially important during fasting?
Gluconeogenesis is especially important during longer fasting or starvation because direct glucose reserves meet needs for only about a day.
What is the Cori cycle?
The Cori cycle links lactate from anaerobic glycolysis in red blood cells and exercising muscle to gluconeogenesis in the liver, regenerating glucose.
Which enzyme is the rate-limiting step of gluconeogenesis?
Fructose-1,6-bisphosphatase is the rate-limiting enzyme of gluconeogenesis.
List key features of pyruvate carboxylase.
Mitochondrial enzyme; activated allosterically by acetyl-CoA; uses ATP and biotin; increased by cortisol via transcriptional induction.
State two regulatory facts about PEPCK.
PEPCK uses GTP and is transcriptionally activated by cortisol, glucagon, and thyroxine.
How is fructose-1,6-bisphosphatase regulated?
Activated by cortisol and citrate; inhibited by AMP and fructose-2,6-bisphosphate (F2,6BP).
Where is glucose-6-phosphatase located and in which tissues is it present?
Glucose-6-phosphatase is located in the endoplasmic reticulum lumen and is present in liver, kidneys, small intestine, and pancreas.
How does cellular energy charge affect glycolysis and gluconeogenesis?
Energy charge determines which pathway is most active; glycolysis and gluconeogenesis are reciprocally regulated.
What is the basic structural composition of glycogen?
Which glycosidic bonds form the linear chains and branch points in glycogen?
What are the ends of a glycogen molecule and what protein primes its synthesis?
Where is glycogen primarily stored and what is its role in liver versus muscle?
What is the first step (trapping and activation) of glycogen synthesis and which enzymes are involved?
Which enzyme performs elongation during glycogen synthesis and what is its role?
Which enzyme creates branch points in glycogen and what bond does it form?
What is the rate-limiting enzyme of glycogenolysis and what cofactor does it use?
Which enzyme converts glucose-1-phosphate to glucose-6-phosphate during glycogen breakdown?
What is the role of the debranching enzyme in glycogenolysis?
How does biotin deficiency affect gluconeogenesis?
What enzyme deficiency causes Von Gierke disease (GSD Ia) and how does it affect glucose release?
What are the two key enzymes that control glycogen synthesis and degradation?
Name three shared regulatory mechanisms for glycogen synthase and glycogen phosphorylase.
How is liver glycogen phosphorylase regulated by glucose and AMP?
How is muscle glycogen phosphorylase regulated by AMP, ATP, and glucose-6-phosphate?
What is the reciprocal relationship between glycogen synthase and glycogen phosphorylase when one is activated?
Activation of one enzyme coincides with inhibition of the other (effects in opposite directions).
Which state favors glycogenesis and what are the hormonal and energetic conditions?
The fed state favors glycogenesis: blood glucose high, insulin high, cellular ATP high.
In the fed state, what are the phosphorylation states and activities of glycogen synthase and glycogen phosphorylase?
Which conditions favor glycogenolysis and which signals mediate it in liver and muscle?
Fasting (low glucose, high glucagon) and exercise (high Ca2+ and AMP in muscle) favor glycogenolysis.
When glycogen breakdown is favored, what are the phosphorylation states and activities of the two enzymes?
How does liver differ from muscle in handling glucose-6-phosphate after glycogenolysis?
How does insulin signaling promote glycogen synthesis at the molecular level?
Insulin activates PKB which activates PP1 and inactivates GSK3; PP1 dephosphorylates glycogen synthase (activating it) and dephosphorylates glycogen phosphorylase (inactivating it).
How do glucagon and epinephrine promote glycogen breakdown via second messengers?
They raise cAMP and activate PKA, which phosphorylates glycogen synthase (inactivating it), activates phosphorylase kinase, and promotes activation of glycogen phosphorylase, causing glycogen breakdown.
What is the primary defect and clinical consequence of GSD 0?
GSD 0 is glycogen synthase deficiency; patients cannot synthesize/store glycogen and are vulnerable to fasting hypoglycemia.
What enzyme is deficient in GSD Ia (Von Gierke disease) and name three clinical features?
Deficiency of glucose-6-phosphatase; features: marked fasting hypoglycemia, lactic acidosis, hepatomegaly.
What enzyme deficiency causes GSD II (Pompe disease)?
Acid maltase (lysosomal α-glucosidase) deficiency
What is the primary pathological consequence of Pompe disease (GSD II)?
Glycogen accumulates in lysosomes causing progressive muscle weakness and myopathy, including heart muscle
How is glycogen structurally altered in Andersen disease (GSD IV)?
Glycogen has long chains with fewer branches
Name two major clinical consequences of Andersen disease (GSD IV).
Give an overview statement of the citric acid (TCA) cycle's role.
The TCA cycle is a biochemical hub that oxidizes carbon fuels to harvest high-energy electrons, is amphibolic, supplies biosynthetic precursors, and occurs inside mitochondria
What are the products from oxidation of a 2-carbon acetyl unit in the TCA cycle?
2 moles of CO2, 1 mole of GTP, and high-energy electrons as NADH and FADH2
Where are energy nutrients converted before entering the TCA cycle?
Energy nutrients are degraded to an acetyl-CoA pool, and acetyl-CoA enters the TCA cycle
How does oxidative phosphorylation relate to the TCA cycle?
Oxidative phosphorylation in mitochondria uses TCA-derived high-energy electrons to produce ATP
How does pyruvate enter mitochondria for PDH to act on it?
Pyruvate enters mitochondria through the mitochondrial pyruvate carrier
What reaction does the pyruvate dehydrogenase complex (PDC) catalyze?
Decarboxylation of pyruvate to form acetyl-CoA with production of CO2 and NADH
How many enzymes and coenzymes are required by the PDC?
The reaction requires 3 enzymes (E1, E2, E3) and 5 coenzymes: TPP, lipoic acid, FAD, CoA, and NAD+
What is the metabolic link function of PDH?
PDH links glycolysis to the citric acid cycle by converting pyruvate to acetyl-CoA
How do high acetyl-CoA and PDH products affect PDH regulation?
High acetyl-CoA directly inhibits E2, and PDH products increase phosphorylation (inactivating PDH)
Which molecules activate phosphatases that stimulate PDH during muscle contraction?
ADP and pyruvate activate phosphatases; Ca2+ stimulates phosphatases during muscle contraction
List the core enzymes of the citric acid cycle.
What reaction does citrate synthase catalyze in the TCA cycle?
Condensation of oxaloacetate with acetyl-CoA to form citrate
Which TCA enzyme is described as the rate-limiting step and how is it regulated?
Isocitrate dehydrogenase is the rate-limiting step; it is allosterically stimulated by ADP and inhibited by NADH
How is α-ketoglutarate dehydrogenase regulated?
It is inhibited by its products succinyl-CoA and NADH and is regulated similarly to PDH
Which two enzymes integrate the TCA cycle with other pathways?
What is the role of anaplerotic reactions in the citric acid cycle?
Anaplerotic reactions 'fill up' and replenish TCA cycle intermediates used for biosynthesis.
Name the two major anaplerotic reactions shown.
Which reaction forms oxaloacetate to replenish TCA intermediates?
Formation of oxaloacetate from pyruvate (pyruvate carboxylation).
List key structural features of mitochondria relevant to metabolism.
What makes the outer and inner mitochondrial membranes different?
Outer membrane is permeable due to porin/VDAC; inner membrane is impermeable, contains metabolite transporters, and is folded into cristae.
Which mitochondrial compartment contains the TCA cycle and fatty acid oxidation?
The mitochondrial matrix is the site of the TCA cycle and fatty acid oxidation.
What features describe mitochondrial genetics and inheritance?
Mitochondria are semi-autonomous with their own DNA, and human mitochondrial DNA is maternally inherited.
What are the three requirements for successful oxidative phosphorylation?
Briefly describe the flow of electrons and protons in oxidative phosphorylation.
High-energy electrons from NADH and FADH2 flow through ETC complexes, reduce O2 to water, three complexes pump protons to the intermembrane space, and protons return through ATP synthase to make ATP.
What is the function of Complex I in the electron transport chain?
Complex I (NADH-Q oxidoreductase) is the first entry point for electrons from NADH.
What distinguishes Complex II from other ETC complexes?
Complex II (succinate-Q reductase) connects the TCA cycle to OxPhos and does not pump protons.
What is the role of Complex III in the electron transport chain?
Complex III (Q-cytochrome c oxidoreductase) transfers electrons from QH2 to cytochrome c and contributes to proton translocation.
What is the role of Complex IV in the electron transport chain?
Complex IV (cytochrome c oxidase) transfers electrons from reduced cytochrome c to molecular oxygen and reduces it to water.
Name the two mobile electron carriers in the electron transport chain.
Where do electrons from NADH enter the mitochondrial electron-transport chain?
Electrons from NADH enter at Complex I, then pass to coenzyme Q, Complex III, cytochrome c, and Complex IV where O2 is the final acceptor.
Where do electrons from FADH2 enter the electron-transport chain?
Electrons from FADH2 enter through Complex II, pass to coenzyme Q, then through Complex III and Complex IV to O2.
Why does oxidation of FADH2 yield less ATP than NADH?
Because Complex II does not pump protons, oxidation of FADH2 contributes fewer pumped protons and thus less ATP synthesis.
What is the final electron acceptor in the mitochondrial electron-transport chain?
Molecular oxygen (O2) is the final electron acceptor at Complex IV.
What reactive oxygen species do mitochondria generate?
Mitochondria generate superoxide free radicals.
What damage can toxic oxygen derivatives and free radicals cause?
They can damage macromolecules and contribute to various pathologies.
What reaction does superoxide dismutase catalyze?
Superoxide dismutase converts superoxide to oxygen and hydrogen peroxide.
Name other antioxidant systems listed.
Other antioxidant systems include glutathione peroxidase, thioredoxin, vitamin E, and vitamin C.
State the chemiosmotic hypothesis in brief.
The electron-transport chain translocates protons across the inner membrane as electrons flow, generating a proton-motive force (∆pmf) used by ATP synthase to phosphorylate ADP.
What are the components of the proton-motive force (∆pmf)?
The proton-motive force is composed of a pH gradient (ΔpH) and a membrane potential (ΔΨ).
Why does disruption of the inner mitochondrial membrane prevent ATP synthesis?
The inner membrane is impermeable to H+ and OH−; if disrupted an Δpmf cannot be established, so ATP synthesis does not occur.
Describe the main structural sectors of ATP synthase (Complex V).
ATP synthase has an F0 membrane-embedded proton channel and an F1 sector protruding into the matrix containing catalytic domains.
What is the subunit composition of the F1 sector and which subunits are catalytic?
The F1 sector contains a3β3γδε; α and β alternate in a hexameric ring, and only the β subunits are catalytically active.
How many protons are approximately required to synthesize one ATP via ATP synthase?
About 3+1 H+ passage is required per ATP synthesized.
Besides catalysis, what structural role do ATP synthase oligomers have?
ATP synthase molecules form dimers and oligomers that help maintain cristae curvature.
What problem do shuttle systems solve for mitochondrial metabolism?
Reduced NADH cannot cross the mitochondrial membrane, so shuttle systems transfer reducing equivalents into mitochondria.
Name the two shuttle systems that move high-energy reducing equivalents into mitochondria.
How do ATP levels affect cellular respiration?
Cellular respiration is regulated by ATP levels; electron flow through the ETC occurs only when ADP is phosphorylated to ATP.
What is 'respiratory control' (acceptor control)?
Regulation of electron transport by ADP levels, where ADP availability controls ETC activity.
What happens to proton pumping and ATP synthesis when electron transport is inhibited?
Inhibition of electron transport decreases proton pumping, lowers the proton gradient, and inhibits ATP synthesis.
What is the mechanism of action of oligomycin on mitochondria?
Oligomycin inhibits ATP synthase (Complex V) by disrupting proton transport through its channel.
How do inhibitors that block electron transport affect ATP synthesis?
They decrease proton pumping and the H+ gradient, which leads to inhibition of ATP synthesis.
What is the difference between blocking electron flow and blocking Complex V in terms of respiration?
Targeting different ETC components either directly blocks electron flow (upstream) or blocks ATP synthesis at Complex V while electron flow may continue.
How does uncoupling affect ATP production and heat generation?
In uncoupling, protons re-enter without ATP synthesis; TCA cycle and electron transfer accelerate and energy is released as heat instead of ATP.
What role does UCP1 (thermogenin) in brown adipose tissue play?
UCP1 transfers protons from the cytoplasm to the matrix, converting proton-motive energy into heat rather than ATP.
Where does the Pentose Phosphate Pathway (PPP) branch from in carbohydrate metabolism?
The PPP branches from glucose-6-phosphate, linking it to glycogenesis/glycogenolysis, glycolysis/gluconeogenesis, and the PPP.
Which glycolytic intermediates are interconverted with PPP sugars in the nonoxidative phase?
Why is NADPH needed in cells?
NADPH is required for synthesis of monomers and for cellular reducing power.
What maintains the reduced glutathione (GSH) pool in healthy cells?
Regeneration of GSH using NADPH, maintaining a GSH:GSSG ratio of about \(500:1\).
What happens to cells when NADPH production is insufficient?
Cells cannot maintain redox homeostasis well and become vulnerable to oxidative damage.
Name a clinical condition resulting from impaired NADPH production in red blood cells.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which can cause acute hemolysis, chronic hemolytic anemia, and neonatal jaundice.
What is the rate-limiting enzyme of the oxidative phase of the Pentose Phosphate Pathway?
Glucose-6-phosphate dehydrogenase (G6PD).
What reaction does glucose-6-phosphate dehydrogenase catalyze?
Oxidizes glucose-6-phosphate to a lactone and reduces NADP+ to NADPH.
Which oligomeric forms of G6PD are active or inactive?
Active forms are dimer and tetramer; the monomer is inactive.
List activators of G6PD activity mentioned in the notes.
List inhibitors of G6PD activity mentioned in the notes.
What are the three reactions of the oxidative phase of the Pentose Phosphate Pathway?
What is the role of the nonoxidative phase of the Pentose Phosphate Pathway?
It shuffles carbons: converts ribulose-5-phosphate to ribose-5-phosphate and xylulose-5-phosphate and transfers 2- and 3-carbon units via transketolase and transaldolase.
How can the Pentose Phosphate Pathway be adjusted to meet different cellular needs?
What are the structural features of a fatty acid?
A fatty acid consists of a hydrocarbon chain plus a carboxyl group and is the primary hydrophobic determinant in lipids.
Why are fatty acids and lipids described as amphipathic?
Because they contain both a hydrophobic part (hydrocarbon) and a hydrophilic part (carboxyl group).
How do saturated and unsaturated fatty acids differ structurally and in melting point?
Saturated fatty acids have no C=C bonds, are more linear, and have higher melting points; unsaturated fatty acids contain cis/trans double bonds, are bent, and generally have lower melting points.
Give common names for these fatty acids: 18:0, 18:1, 18:2, 18:3.
Which two omega fatty acids cannot be synthesized by humans?
Are ALA and LA efficiently converted to EPA, DHA, and arachidonic acid?
List three important roles of omega fatty acids.
According to the Fluid Mosaic Model, what are membrane lipids described as?
What are the majority lipid components of cell membranes?
What is Phase I of fatty acid synthesis?
What reaction defines Phase II of fatty acid synthesis and which enzyme catalyzes it?
What is Phase III of fatty acid synthesis?
Where does elongation of fatty acids beyond C16 occur and what substrates are used?
Elongation occurs on the endoplasmic reticulum by fatty acid elongase using malonyl-CoA and NADPH.
Which enzymes catalyze desaturation of fatty acids in humans?
Desaturation is catalyzed in the smooth ER by NADH-cytochrome b5 reductase, cytochrome b5, and a desaturase.
At which carbon positions can humans introduce double bonds in fatty acids?
Humans can introduce double bonds only at Δ4, Δ5, Δ6, and Δ9 (A4, A5, A6, and A9).
Why are some fatty acids essential in the human diet?
Double bonds beyond carbon 9/10 cannot be synthesized by humans, so those fatty acids must come from the diet.
Which enzymes are the main regulatory targets in fatty acid synthesis?
The main targets are ATP citrate lyase, acetyl-CoA carboxylase (ACC), and fatty acid synthase.
Which ACC oligomeric state is active and which is inactive?
The polymer of ACC is active; the monomer/dimer is inactive.
Name inhibitors of ACC and the pathways that mediate inhibition.
How does diet affect gene expression of the fatty acid synthesis pathway?
A high-carbohydrate/low-fat diet up-regulates gene expression of the pathway.
List the sequential intermediates in TAG synthesis from glycerol-3-phosphate.
How do liver and adipocytes differ in sources used for TAG synthesis?
In liver, glucose and glycerol provide glycerol-3-phosphate and newly synthesized FAs form TAGs for VLDL. In adipocytes, FAs from chylomicrons and VLDL are added to glycerol-3-phosphate for storage.
Which hormones promote TAG synthesis in hepatocytes?
TAG synthesis in hepatocytes is promoted by excess carbohydrates (metabolic state), not a specific hormone listed.
Which hormones promote breakdown of stored triacylglycerols (lipolysis)?
Name the three major lipases involved in triacylglycerol breakdown.
How are fatty acids transported in blood after release from adipose tissue?
Short-chain fatty acids are soluble in blood; long-chain fatty acids are transported bound to albumin.
What is Phase I of fatty acid breakdown?
Activation and transport of fatty acids to the mitochondrial matrix.
Which enzyme activates long-chain fatty acids on the outer mitochondrial membrane?
Fatty acyl-CoA synthetase
Name the transport steps and proteins that move fatty acids into the mitochondrial matrix.
List the four enzymatic steps of ß-oxidation in mitochondria.
Which enzyme is the rate-limiting step in fatty acid degradation?
Carnitine palmitoyltransferase I (CPT-I)
How does malonyl-CoA affect fatty acid breakdown?
Malonyl-CoA inhibits CPT-I, preventing fatty acid degradation.
How is hormone-sensitive lipase (HSL) regulated by hormones?
HSL is activated by PKA-mediated phosphorylation (glucagon/epinephrine) and inhibited by insulin via PP1-mediated dephosphorylation.
Why does ketone body formation increase during fasting?
Low carbohydrate availability lowers oxaloacetate, so excess acetyl-CoA from ß-oxidation condenses to form ketone bodies.
How does diabetic ketoacidosis develop in terms of hormone ratio and metabolism?
An increased glucagon/insulin ratio with impaired carbohydrate metabolism favors fatty acid breakdown, increasing hepatic acetyl-CoA and ketone formation.
Which ketone bodies lower blood pH and cause acidosis?
Acetoacetate and ß-hydroxybutyrate are strong acids that lower blood pH and cause acidosis.
What causes the fruity breath odor in uncontrolled diabetes?
Volatile acetone is exhaled in breath and gives the fruity odor.
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