exam 2 biochem

Explain how PDH converts pyruvate to acetyl CoA

Pyruvate dehydrogenase (PDH) catalyzes the conversion of pyruvate to acetyl CoA by decarboxylating pyruvate, releasing carbon dioxide, and transferring the remaining two-carbon unit to coenzyme A. This process also involves the reduction of NAD+ to NADH, linking glycolysis to the citric acid cycle.

Why does thiamine mean deficiency raise lactate?

Thiamine deficiency impairs the activity of pyruvate dehydrogenase (PDH), leading to the accumulation of pyruvate. When PDH is inactive, pyruvate is converted to lactate instead of being transformed into acetyl CoA, resulting in increased lactate levels.

Why is thiamine giving before or with carbohydrate to patients at risk of deficiency?

Thiamine is given before or with carbohydrates to patients at risk of deficiency to prevent the impairment of pyruvate dehydrogenase (PDH) activity. This helps ensure proper metabolism of carbohydrates, reducing the risk of lactate accumulation and associated complications.

Identify where the TCA cycle produces NADH, FADH2, GTP, AND CO2

The TCA cycle produces NADH at three steps: isocitrate to α-ketoglutarate, α-ketoglutarate to succinyl CoA, and malate to oxaloacetate. FADH2 is produced from succinate to fumarate, GTP (or ATP) is generated during succinyl CoA to succinate, and CO2 is released during isocitrate to α-ketoglutarate and α-ketoglutarate to succinyl CoA.

Connect NADH and FADH2 to their entry points in the electron transport chain

NADH donates electrons at Complex I, while FADH2 donates electrons at Complex II of the electron transport chain. This process contributes to the production of ATP through oxidative phosphorylation.

Calculate the approximate ATP yield from one acetyl-CoA and one pyruvate

One acetyl-CoA yields approximately 10 ATP through the TCA cycle and electron transport chain, while one pyruvate can yield around 12.5 ATP after conversion to acetyl-CoA and subsequent reactions.

Explain why a small amount of oxoloacetate can support many terms of the cycle

A small amount of oxaloacetate can support multiple turns of the TCA cycle because it is regenerated after each cycle through the conversion of succinate to oxaloacetate, allowing continuous participation in the cycle without the need for large quantities.

Explain how ATP demand and NAD+ regeneration affect TCA cycle flux

In conditions of high ATP demand, NAD+ regeneration becomes crucial for maintaining TCA cycle flux, as ATP synthesis relies on the availability of oxidized NAD+. When ATP levels are low, NAD+ is regenerated from NADH during lactate formation or other anaerobic processes, enhancing TCA cycle activity.

Predict how impaired ETC affects the mitochondria NADH/NAD+ ratio, TCA cycle flux and lactate

When the ETC is impaired, NADH accumulates, which shuts down the TCA cycle from a lack of NAD+, forcing pyruvate into lactate production to keep anaerobic glycolysis running.

Explain why intermediates leaving the TCA cycle must be replaced and how pyruvate carboxylase replenishes oxaloacetate

drawing intermediates out of the TCA cycle drains the oxaloacetate needed to keep the cycle turning, pyruvate carboxylase uses ATP and biotin to add CO2 to pyruvate, directly restocking oxaloacetate so acetyl-CoA can keep entering.

Explain why acetyl-CoA cannot replenish the cycle and why fasting promotes hepatic ketone body production

Acetyl-CoA can't replenish the TCA cycle because its two carbons are lost as CO2​, so during fasting—when gluconeogenesis drains oxaloacetate and β-oxidation floods the liver with acetyl-CoA, the excess acetyl-CoA is shunted into ketone body production.

Identify the major lipid classes and explain how the structure of each suits its function

Triacylglycerols store dense energy in hydrophobic tails,

phospholipids form protective cell membranes via amphipathic bilayers,

steroids regulate fluidity and signaling with rigid ring systems,

sphingolipids provide neural insulation and cell recognition through specialized sphingosine backbones.

Explain why lipids mix poorly with water and white phospholipids formed by layers while triacylglycerols form droplets

clustering nonpolar molecules increases water's entropy, driving amphipathic phospholipids (with polar heads and nonpolar tails) to form cell-membrane bilayers, while completely nonpolar triacylglycerols coalesce into hydrophobic oil droplets.

interpret simple fatty acid notation and explain how cyst double bonds affect chain packing and membrane fluidity

Fatty acid notation (C:D Δn) indicates carbon count and double-bond locations, where cis double bonds introduce structural kinks that prevent tight chain packing, lowering the melting point and increasing membrane fluidity.

Identify the two essential fatty acids and explain why they must come from the diet

Linoleic acid w-6 and alpha-linolenic acid w-3 are essential fatty acids that must come from the diet because human cells lack the delta12 and delata15 desaturases needed to place double bonds past carbon-9.

Explain the structure, triacylglycerol and why they are efficient energy stores

Triacylglycerols composed of three fatty acids esterified to glycerol are ideal energy stores because their hydrocarbon chains are fully reduced (yielding maximum ATP per gram) and anhydrous (storing compact energy without extra water weight).

Describe how fast lipids, cholesterol and proteins are arranged in membranes, including how lipids anchor proteins

membranes consist of an amphipathic phospholipid bilayer fluidly buffered by cholesterol and embedded with proteins, which can be permanently or reversibly anchored to the hydrophobic core using lipid tags like prenyl groups, myristoyl/palmitoyl fatty acids, or GPI anchors.

explain how pulmonary surfactant reduces alveolar surface tension

Pulmonary surfactant lowers surface tension by inserting amphipathic DPPC between surface water molecules to disrupt hydrogen bonding, packing tightly during expiration to prevent small alveoli from collapsing

Identify the principle function of cholesterol

cholesterol is to regulate cell membrane fluidity and structural integrity across temperatures while serving as the precursor for steroid hormones, bile acids, and vitamin D

Explain how arachidonic acid gives rise to signaling molecules and why low-dose aspirin has a prolonged anti-platelet effect

Arachidonic acid is cleaved by PLA2 to generate inflammatory eicosanoids via COX (prostaglandins, thromboxanes) and LOX (leukotrienes) pathways, and low-dose aspirin provides a prolonged anti-platelet effect by irreversibly acetylating COX-1 in anucleate platelets, permanently blocking thromboxane A2 production for their 7-10 day lifespan

Identify vitamins, A, D, E, and K and explain how they connect to fat absorption orlistat and warfarin

Vitamins A, D, E, and K are hydrophobic lipids that require pancreatic lipases and mixed micelles for intestinal absorption—meaning orlistat causes their malabsorption by inhibiting lipases, while warfarin selectively blocks Vitamin K recycling via VKORC1 to prevent the gamma-carboxylation of clotting factors II, VII, IX, and X

Compare fatty acid metabolism in the fed and fasting states, including hormonal regulation.

In the fed state, insulin promotes fatty acid synthesis via acetyl-CoA carboxylase (ACC), whereas during fasting, glucagon drives lipolysis via hormone-sensitive lipase (HSL) and promotes beta-oxidation

Explain how stored triacylglycerols are broken down and how fatty acids and glycerol are transported and used.

Hormone-sensitive lipase breaks down stored triacylglycerols into free fatty acids (transported to tissues bound to albumin) and glycerol (transported to the liver for gluconeogenesis).

Explain fatty acid activation and the role of the carnitine shuttle in mitochondrial transport.

Fatty acids are activated to acyl-CoA in the cytosol using 2 ATP equivalents, and carnitine palmitoyltransferase-1 (CPT-I) attaches carnitine to transport them across the inner mitochondrial membrane.

Describe the four reactions of β-oxidation and identify their major products

$\beta$-oxidation shortens fatty acyl-CoAs through oxidation, hydration, oxidation, and thiolysis, producing 1 acetyl-CoA, 1 FADH2, and 1 NADH per cycle.

Calculate the approximate ATP yield from complete oxidation of palmitate and explain why fat is an energy-dense fuel

Complete oxidation of palmitate yields a net 106 ATP, making fats extremely energy-dense because their carbons are fully reduced and stored anhydrously without water weight.

Explain the major steps of fatty acid synthesis and the roles of acetyl-CoA, ACC, malonyl-CoA, fatty acid synthase, ATP, and NADPH.

Synthesis occurs in the cytosol using citrate-derived acetyl-CoA, where ACC forms malonyl-CoA and fatty acid synthase uses ATP and NADPH to assemble palmitate.

Explain how malonyl-CoA coordinates fatty acid synthesis and oxidation through inhibition of CPT-I

Malonyl-CoA produced during fatty acid synthesis allosterically inhibits CPT-I, preventing newly made fatty acids from entering the mitochondria to undergo $\beta$-oxidation.

Predict the metabolic consequences of impaired fatty acid oxidation, using carnitine deficiency and MCAD deficiency as examples

Blocked fatty acid oxidation from carnitine or MCAD deficiency halts energy production and gluconeogenesis during fasting, causing severe hypoketotic hypoglycemia.

Explain why the liver converts acetyl-CoA into ketone bodies during fasting rather than oxidizing
all of it in the TCA cycle.

During fasting, high glucagon causes the liver to drain oxaloacetate for gluconeogenesis, preventing acetyl-CoA (generated by heavy beta-oxidation) from entering the TCA cycle and forcing its diversion into ketone bodies.

Name the three ketone bodies, state which two are fuels, and describe how acetone forms.

The three ketone bodies are acetoacetate and beta-hydroxybutyrate (which serve as usable metabolic fuels) plus acetone, a volatile waste product formed by the spontaneous or enzymatic decarboxylation of acetoacetate.

Explain why the liver makes ketone bodies but cannot use them, and how other tissues oxidize them

The liver synthesizes ketone bodies but cannot oxidize them because it lacks thiophorase (beta-ketoacyl-CoA transferase), forcing ketones into circulation for extrahepatic tissues to convert back into acetyl-CoA for ATP production.

Describe how the brain's use of ketone bodies during prolonged fasting spares glucose and body protein.

During prolonged starvation, the brain adapts to burn ketone bodies for up to 70% of its energy needs, drastically lowering its demand for glucose and preserving muscle protein from amino acid breakdown.

Distinguish physiological ketosis from diabetic ketoacidosis (DKA) and explain how insulin deficiency leads to DKA.

Physiological ketosis is a controlled, self-limiting fasting response, whereas diabetic ketoacidosis (DKA) occurs in complete insulin deficiency where uninhibited lipolysis floods the liver with fatty acids, driving massive ketone overproduction that overpowers blood buffers and causes severe metabolic acidosis.

Explain how SGLT2 inhibitors can cause euglycemic ketoacidosis (EDKA).

SGLT2 inhibitors promote glucosuria to lower blood glucose, which triggers a fall in insulin and a rise in glucagon that drives lipolysis and hepatic ketogenesis even while blood glucose remains normal <250mg/dL

Outline cholesterol synthesis from acetyl-CoA and identify HMG-CoA reductase as the major regulated step in cholesterol synthesis

Cholesterol is assembled in the cytosol from acetyl-CoA, and its primary rate-limiting and strictly regulated step is catalyzed by HMG-CoA reductase, which converts HMG-CoA into mevalonate

Explain how cellular cholesterol availability regulates both cholesterol synthesis and hepatic LDL receptor expression.

Low intracellular cholesterol causes the SREBP-2/SCAP complex to enter the nucleus and upregulate transcription of both HMG-CoA reductase (to boost synthesis) and LDL receptors (to increase clearance of circulating LDL).

Explain how statins lower circulating LDL cholesterol; recognize ATP-citrate lyase as the target of bempedoic acid

Statins lower circulating LDL by competitively inhibiting HMG-CoA reductase—triggering liver cells to upregulate membrane LDL receptors to clear LDL from plasma—while bempedoic acid targets the upstream enzyme ATP-citrate lyase to block cytosolic acetyl-CoA supply.

Explain why excess amino nitrogen must be eliminated, mainly as urea

Excess amino nitrogen must be excreted as urea because free ammonia (NH4+) is highly toxic to human tissues, and humans lack the metabolic machinery to store or exhale nitrogenous waste products.

Describe transamination, including the roles of α-ketoglutarate, glutamate and pyridoxal phosphate (vitamin B6), and distinguish it from oxidative deamination, which releases NH₄⁺.

Transamination uses pyridoxal phosphate (vitamin B6) to transfer an amino group from an amino acid to alpha-ketoglutarate (forming glutamate) without releasing free ammonia, whereas oxidative deamination (catalyzed by glutamate dehydrogenase) directly cleaves glutamate to release toxic NH4+

Explain what ALT and AST do, why their levels in the blood rise when cells are damaged, and why
neither is a direct test of liver function.

ALT and AST are intracellular transaminases that spill into the bloodstream upon cell damage or necrosis, making them markers of hepatocellular injury rather than direct tests of liver function (which requires measuring synthetic products like albumin or coagulation factors).

Explain how glutamine and alanine carry nitrogen to the liver, including the glucose–alanine cycle.

Glutamine carries excess tissue nitrogen safely to the liver, while the glucose–alanine cycle transfers muscle nitrogen as alanine to the liver for conversion into urea and glucose (which returns to muscle).

Describe the urea cycle in outline: where it occurs, where the two nitrogens of urea come from, and
the roles of CPS I, N-acetylglutamate and OTC.

Occurring across the mitochondrial matrix and cytosol of hepatocytes, the urea cycle derives its two nitrogens from free ammonia (via CPS I, activated allosterically by N-acetylglutamate) and aspartate, with ornithine transcarbamylase (OTC) combining carbamoyl phosphate with ornithine.

Interpret changes in blood urea nitrogen (BUN) in kidney and liver dysfunction.

Blood Urea Nitrogen (BUN) rises in kidney dysfunction due to reduced renal excretion and filtration, but drops in severe liver dysfunction because damaged hepatocytes can no longer synthesize urea from ammonia.

Explain why high blood ammonia (hyperammonemia) harms the brain, name its main causes (including
valproate), and explain the reasoning behind treatment of an inherited urea-cycle disorder.

High ammonia depletes brain alpha-ketoglutarate and drives neurotoxic glutamine accumulation (caused by liver failure, valproate, or genetic enzyme deficiencies), requiring treatment with nitrogen scavengers (e.g., sodium phenylbutyrate) to excrete nitrogen independently of the urea cycle.

Explain how lactulose and rifaximin lower ammonia in hepatic encephalopathy.

Lactulose is metabolized by colonic bacteria into organic acids that trap toxic NH3 as unabsorbable NH4+ in the gut, while rifaximin kills ammonia-producing enteric bacteria to reduce systemic ammonia burden in hepatic encephalopathy.

Distinguish glucogenic from ketogenic amino acids.

Glucogenic amino acids are catabolized into TCA cycle intermediates or pyruvate to fuel gluconeogenesis, whereas ketogenic amino acids (exclusively leucine and lysine) are degraded into acetyl-CoA or acetoacetate and can only yield ketone bodies or fatty acids.

Cyanide vs. DNP

Cyanide directly inhibits Complex IV to block the electron transport chain and halt oxygen consumption, whereas DNP uncouples the proton gradient, causing the electron transport chain to run uncontrollably at maximum speed and consume more oxygen to dissipate energy as heat.

Blocking ATP Synthase

stops proton re-entry into the matrix, causing protons to back up in the intermembrane space until the high electrochemical gradient (delta p) creates a resistance that halts further electron transport.

RBC vs. Cardiac Muscle ATP

Cardiac muscle cells contain mitochondria equipped for oxygen-dependent oxidative phosphorylation, whereas mature red blood cells lack mitochondria entirely and rely solely on anaerobic glycolysis for ATP.

Succinate Dehydrogenase (Complex II)

NADH-derived electrons enter the electron transport chain at Complex I and flow through Complexes III and IV independently of succinate dehydrogenase (Complex II), which only receives electrons from FADH2 (succinate).

NADH Accumulation from Complex IV Inhibition

Inhibiting Complex IV blocks the final transfer of electrons to oxygen, causing the upstream complexes (Complex I, III, CoQ) to remain fully reduced and preventing Complex I from oxidizing NADH back to NAD+.

Source of Mitochondrial NADH and FADH2

Most mitochondrial NADH and FAD-linked electrons (FADH2) originate from the TCA cycle (fueled by acetyl-CoA from pyruvate, fatty acid Beta-oxidation, and amino acid catabolism).

Complex I (NADH-Ubiquinone Oxidoreductase)

Complex I oxidizes mitochondrial NADH, transferring two electrons through FMN and Fe-S clusters to coenzyme Q while pumping 4 protons into the intermembrane space (inhibited by rotenone and amobarbital).

Complex II (Succinate-Ubiquinone Reductase)

Complex II (succinate dehydrogenase) links the TCA cycle directly to the ETC by transferring electrons from succinate-derived FADH2 to coenzyme Q without pumping any protons across the membrane.

Complex III (Coenzyme Q-Cytochrome c Reductase)

Complex III transfers electrons from reduced coenzyme Q (QH2) to cytochrome c via the Q cycle, pumping 4 protons into the intermembrane space (inhibited by antimycin A).

Complex IV (Cytochrome c Oxidase)

Complex IV transfers four electrons from reduced cytochrome c to molecular oxygen (O2) to form two H2O molecules while pumping 2 protons per electron pair (inhibited by cyanide, carbon monoxide, and sodium azide).