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134 Cards in this Set

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  • Back
What is another word for fat stored in fat cells?
What are the two circumstances lead to obesity, especially childhood obesity?
More fat storage per cell as well as a larger number of adipocytes.
What are fatty acids stored as, and what are these things composed of?
Fatty acids are are stored as triacylglycerols (triglycerides) which are uncharged esters of glycerol
Why is Acetyl CoA a central intermediate in fat metabolism?
Both catabolic and anabolic pathways utilize acetyl CoA as the activated carrier of the two carbon product or donor.
Triglycerides obtained from food are cleaved by what, and what does this cleavage generate?
Triglycerides obtained from good are cleaved by enzymes called LIPASES in the intestine. Through this, they generate free fatty acids and monoacylglycerols.
After passing through the membrane of mucosal cells that line the intestine, ezymes catalyze the formation of what?
After triglycerides are formed inside the mucosal cell, they are packaged into what?
They are packaged into large lipid rich particles called CHYLOMICRONS.
What are the two purposes of fatty acid metabolism in animals?
Fatty acid metabolism serves in fatty acid OXIDATION and SYNTHESIS.
What is the purpose of fatty acid oxidation?
Fatty acid oxidation is responsible for providing energy to cells when glucose levels are LOW.
How long can triacylglycerols stored in adipose tissue of most humans supply energy to the body for?
They can supply energy to the body for about 3 months during starvation.
What do fatty acid synthesis reactions in the cytosol of the liver and adipose cells do?
They convert EXCESS acetyl CoA that builds up in the mitochondrial matrix when glucose levels are HIGH into fatty acids that can be stored or exported as triacylglycerols.
What is the net reaction of fatty acid degradation for palmitate?
Palmitate + 7 NAD+ + 7 FAD + 8 CoA + 7 H2O + ATP ---> 8 Acetyl CoA + 7 NADH + 7 FADH2 + AMP + 2 Pi + 7H+
What is the net reaction of fatty acid synthesis?
8 Acetyl CoA + 7 ATP + 14 NADPH + 14 H+ ---> Palmitate + 8 CoA + 7 ADP + 7 Pi + 14 NADP+ + 6 H2O
What does "fatty acyl CoA synthetase" do?
It converts free acids in the cytosol into FATTY ACYL-CoA using the energy available from ATP and PPi hydrolysis.
Under what circumstance(s) is fatty acyl-CoA used for fatty acid oxidation inside the mitochondria?
It is used for oxidation inside the mitochondria when energy charge in the cell is low.
Under what circumstance(s) is fatty acyl-CoA used to synthesize triacylglycerols or membrane lipids?
Fatty acyl-CoA is used to synthesize triacylglycerols or membrane lipids when energy charge in the cell is high.
What does carnitine acyltransferase I do?
It catalyzes the commitment step in fatty acid oxidation which links fatty acyl-CoA molecules to the hydroxyl group of carnitine.
What is the activity of carnitine acyltransferase I inhibited by?
It is inhibited by MALONYL CoA.
What is malonyl CoA the product of?
It is the product of the acetyl-CoA carboxylase reaction.
What does a high level of malonyl CoA signify?
It signals that glucose levels are high and fatty acid synthesis is favored.
What does acetyl CoA carboxylase catalyze?
It catalyzes the commitment step in fatty acid synthesis.
What does acetyl CoA carboxylase do to acetyl CoA?
It carboxylates acetyl CoA to form the C3 compound malonyl CoA.
What are the two methods that acetyl CoA carboxylase is regulated?
It is regulated by both reversible phosphorylation and allosteric mechanisms.
What is fatty acid synthase responsible for?
It is responsible for catalyzing a series of reaction that sequentially adds C2 units to a growing fatty acid chain covalently attached to the enzyme complex.
How does the mechanism of fatty acid synthase work?
It involves the linking of malonyl-CoA to an acyl carrier protein, followed by a decarboxylation and condensation reaction that extends the hydrocarbon chain.
What does eating too much of high calorie non-fat foods activate?
It activates fatty acid synthesis pathway resulting in the conversion of acetyl CoA to fatty acids which are stored as triacylglycerols.
What is Olestra composed of?
It is composed of a sucrose molecule with several fatty acids attached.
What does Orlistat do?
It binds to and inhibits pancreatic lipase activity in the intestine.
What is a major reason involving glycogen that causes fatty acids stored in adipose cells to be released into the blood?
During strenuous exercise and dieting, these fatty acids are released in order to provide a rich source of energy for tissues throughout the body when glycogen stores have been depleted.
Which end are fatty acid carbons numbered by?
They are numbered starting at the carboxy terminus.
What is the methyl carbon atom at the distal (opposite) end called?
It is called the omega carbon.
How is the position of double bonds denoted in fatty acids?
Double bonds are denoted from the carboxy end using a delta sign followed by a superscript number (e.g., cis-Delta9-hexadecenoate). Another way they can be named is from the CH3 terminal end using the omega carbon (e.g., omega-3 fatty acid).
What are the four major physiologic roles of fatty acids?
They act as building blocks of membrane phospholipids. They are covalently attached to proteins as targeting signals. They act as major fuel molecules in most animals. Derivatives of fatty acids are hormones and intracellular signals.
One gram of anhydrous fat stores how much more energy than a gram of hydrated glycogen?
It stores six times more energy than a gram of hydrated glycogen.
What is the first step in the reactions of fatty acid oxidation?
Triacylglycerols are first hydrolized by lipases to release glycerol and free fatty acids.
What type of changes in Lipase accommodate fatty acid binding?
Conformation changes accommodate fatty acid binding in Lipase.
After glycerol has been produced by the hydrolysis of triacylglycerols, it is further metabolized to what following phosphorylation and dehydrogenation?
It is metabolized to dihydroxyacetone phosphate (DHAP)
Fatty acids are activated by what through an activation process on the outer mitochondria membrane in order to form fatty acyl CoA?
Fatty acids are activated by the enzyme acyl CoA synthetase.
The reaction generating fatty acyl CoA is driven by what?
It is generated by the hydrolysis of inorganic phosphate.
Fatty acyl CoA derivatives are carried across the inner mitochondrial membrane by conjugation to what?
The carrier process moving acyl CoA derivatives across the inner mitochondrial membrane requires what two carrier processes?
Once inside the mitochondrial matrix, fatty acids are oxidized how many carbons at a time?
Fatty acids are oxidized two carbons at a time once inside the mitochondrial matrix.
What does the oxidation of fatty acids inside the mitochondrial matrix release?
It releases acetyl CoA, NADH, and FADH2.
What is the acronym for the fatty acid oxidation pathway, and what do they stand for?
OHOC, stands for oxidation, hydration, oxidation, thiolysis.
How many rounds of fatty acid oxidation does it require to metabolize palmitate, a C16 fatty acid?
It requires 7 rounds of oxidation.
Each round of fatty acid oxidation releases what?
It releases 2 carbons as Acetyl CoA, and produces 1 NADH and 1 FADH2.
What does ATP and synthesis and the oxidation of NADH and FADH2 yield a large amount of?
It yields a large amount of H2O.
Under what circumstances is acetyl CoA converted to acetoacetyl CoA and ketone bodies?
When fatty acid oxidation produces more acetyl CoA than can be combined with oxaloacetate to form citrate.
What is ketogenesis and where does it primarily take place?
It is the synthesis of ketone bodies and it takes place primarily in the liver.
Ketone bodies produced by the liver are exported where, and for what purpose?
Ketone bodies are exported to places such as the heart muscle, where they are converted back to 2 acetyl CoA units.
If fat is the fuel of the carbohydrate furnace, and if too much fuel is piling up, what occurs?
It is converted to KETONE BODIES and shipped out of the cell.
What is the commitment step in fatty acid synthesis?
The commitment step of fatty acid synthesis is the carboxylation of acetyl CoA to form malonyl CoA by the enzyme acetyl CoA carboxylase.
What does the large protein complex called fatty acid synthase do?
It adds two carbon units sequentially to the growing fatty acid chain.
The sequential addition of C2 units to a growing fatty acid
chain requires bond energy stored in what molecule?
It requires malonyl CoA.
ATP-dependent carboxylation of acetyl CoA by the enzyme acetyl CoA carboxylase forms what?
It forms malonyl CoA.
Malonyl CoA must be covalently attached to what prior to elongation?
It must be attached to acyl carrier protein through sulfhydral linkage at cysteine 163.
What is the first synthesis step after malonyl-ACP has been primed?
It is the condensation of C2 acetyl-ACP with C3 malonyl-ACP, increasing the carbon length by two and releasing 1 molecule of CO2.
The growing fatty acid chain is translocated between what two things?
It is translocated between the condensing enzyme (CE) and the acyl carrier protein (ACP).
What is the net acetyl CoA carboxylase reaction?
7 Acetyl CoA + 7 CO2 + 7 ATP ----> 7 malonyl CoA + 7 ADP + 7 Pi + 14 H+
What is the net fatty acid synthase reaction?
Acetyl CoA + 7 malonyl CoA + 14 NADPH + 20 H+ ----> palmitate + 7 CO2 + 14 NADP+ + 8 CoA + 6 H2O.
What are the combined reactions of fatty acid synthesis?
8 Acetyl CoA + 7 ATP + 14 NADPH + 6 H+ ----> palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 Pi + 6 H2O
What are two activators of fatty acid synthesis?
The two activators are citrate and insulin.
What are the four inhibitors of fatty acid synthesis?
Palmitoyl-CoA, AMP, glucagon, and epinephrine are inhibitors.
What are the two mechanisms that control acetyl CoA carboxylase activity?
Phosphorylation and dephosphorylation as well as allosteric control by citrate binding?
Arachidonate is a C20 unsaturated fatty acid (four double bonds) that is a major precursor to a class of signalling molecules collectively called what?
Eicosanoids (eye-cose-anoids)
Eicosanoids are what type of hormones?
They are local hormones because they activate signalling pathways in nearby cells and are short-lived molecules.
Prostaglandings are a type of eicosanoids that stimulate what?
They stimulate the inflammatory response.
Prostaglandin H2 (PGH2) is a product of an enzymatic reaction catalyzed by what?
Prostaglandin Synthase
What do COX-1 and COX-2 act as target of?
They are target of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen.
How do apirin and ibuprofin inhibit the production of PGH2?
They irreversibly block the cyclooxygenase activity of prostaglandin synthase.
What is COX-2 considered to be the key for?
It is the key pro-inflammatory enzyme in many human pathophysiologies.
COX-1 is an important enzyme where, and what does it produce?
It is an important enzyme in the stomach that produces prostaglandins required for regulation of gastric mucin.
What is a major side effect of aspirin and ibuprofen?
A major side effect is gastrointestinal bleeding due to low amounts of mucin which are required to protect the stomach against acids and pepsin.
Which of the two COX's is called the good isoform?
COX-1 is sometimes called the good isoform.
Which of the two COX's is called the bad isoform, and why?
COX-2 is called the bad isoform because it is responsible for pain and inflammation.
What are cholesterol and triglycerides carried in the blood by?
They are carried in the blood by lipoprotein particles.
What do chylomicrons transport?
They transport dietary lipids to the liver.
What type of cholesterol is high density lipoprotein?
It is a type of cholesterol scavenger.
High lvls of HDL in serum have been studied to show low levels of what?
It has been shown to show low levels of cardiovascular disease.
Is HDL known as the bad or good cholesterol?
It is known as the good cholesterol.
What is the main carrier of cholesterol to the peripheral tissues?
Low Density Lipoprotein (LDL)
Where are LDL receptor proteins found and what do they do?
They are found on liver cells, and they internalize serum LDL and ultimately control the de novo synthesis of cholesterol in the liver by determining how much cholesterol is inside the cell.
Cholesterol esters are formed by what enzyme?
They are formed in the liver by the enzyme acyl CoA-cholesterol acyl transferase (ACAT), which transfers fatty acid from coenzyme A to the hydroxyl group of cholesterol.
How do cholesterol esters enter cells?
They enter cells by receptor-mediated endocytosis.
LDL particles contain which protein that is recognized by receptor proteins on cells called LDL receptors?
LDL particles contain apolipoprotein apoB-100.
Binding of an LDL particle to LDL receptors initiates what?
It initiates an endocytic process in which the LDL particle is transported inside the cell.
Decreased expression of LDL receptors leads to what?
It leads to high levels of serum cholesterol.
Increased expression of LDL receptors decreases what?
It decreases levels of serum cholesterol.
After the LDL receptor has done its job by bringing the LDL particle inside the cell, what does it do?
It is recycled to the cell surface where it can pick up another LDL particle.
Where does the majority of serum-derived cholesterol come from?
It comes from de novo biosynthesis in the liver, not from dietary cholesterol.
Radioisotope labeling experiments have shown that all 27 carbon atoms of cholesterol are derived from what?
Acetyl CoA
What does the synthesis of mevalonate from 3-hydroxy-3-methyl-glutaryl (HMG) CoA require?
It requires the enzyme HMG CoA Reductase.
In the cytosol, HMG-CoA is reduced by what?
It is reduced by HMG CoA reductase to form mevalonate, a precursor to cholesterol biosynthesis.
In the mitochondria, HMG-CoA is split into what?
It is split into acetyl CoA and acetoacetate, a ketone body, by the enzyme HMG CoA cleavage enzyme.
Cholesterol biosynthesis involves the sequential addition of what to form squalene?
It involves the addition of C5 units (isopentenyl pyrophosphate) to form squalene (C30).
The pathway creating squalene consumes wha two things?
It consumes large amounts of ATP and NADPH.
Squalene is cyclized to form what?
It is cyclized to form lanosterol (C30).
Lanosterol is converted to what?
Lanosterol is converted to C27 cholesterol.
What is a more effective way to control cholesterol than trying to control cholesterol levels by diet?
Inhibiting the activity of HMG-CoA reductase in the liver using statin drugs is more effective.
What do bile salts do?
They are highly effective biological detergents that solubilize dietary lipids in the small intestine.
Bile salts are synthesized from what?
They are synthesized from cholesterol.
How does treating high serum cholesterol by removing bile salts work exactly?
It works by ingesting RESINS that bind bile salts and can be excreted.
If you decrease bile salt concentration by ingesting resins, how does this decrease cholesterol in blood serum?
It works because when you decrease bile concentration, your body makes more bile salts through the conversion of cholesterol into bile salts in the liver.
What does decreased expression of LDL receptors in humans lead to?
It leads to familial hypercholesterolemia and artherosclerosis.
What do high levels of serum cholesterol and atherosclerosis lead to?
They lead to severe cardiovascular desease and death.
How do statins work?
They inhibit de novo cholesterol biosynthesis by blocking the committed step catalyzed by HMGCoA reductase.
What are the five major steroid hormones?
The five major steroids are progesterone, androgen, estrogen, glucocorticoid, mineralocorticoid.
What is the primary function of Progesterone?
It prepares the uterus for implantation of ovum.
What is the primary function of Androgen?
It is responsible for male secondary sex characteristics.
What is the primary function of Estrogen?
It is responsible for female secondary sex characteristics.
What is the primary function of Glucocorticoid?
It is responsible for gluconeogensis as well as acting as an anti-inflammatory.
What is the primary function of Mineralcorticoid?
It is responsible for salt balance and kidney functions.
What are two steroid precursors sold at health food stores?
Androstenedione and DHEA (dehydroepiandrosterone)
What does a deficiency in 17-hydroxylase do?
It decreases levels of all steroids except mineralocorticoids. This leads to severe defects in reproductive development.
What does a deficiency in 21-hydroxylase do?
It is the most common defect, which blocks both
mineralocorticoid and glucocorticoid production.
The net result is an increase in androgen production in the adrenal glands causing masculinization of females due to high levels of androgens. Kidney dysfunction due to loss of aldosterone is also a serious problem. This deficiency is known clinically as Congenital Adrenal Hyperplasia (CAH) and is treatable with steroid replacement therapy.
Deficiency in 5a-reductase causes what?
It decreases production of dihydrotestosterone which is the active form of testosterone (DHT is 10x more active than testosterone). The clinical effect is feminization of genetic males at birth with the potential to form male genitalia at the onset of puberty.
Ammonia (NH4+) is a waste product from what?
Amino acid degradation
What is ammonia removed from the body as?
Proteins obtained from the diet are degraded by what?
Intracellular proteins are degraded by what macromolecular?
Proteasomes recognize proteins that have been tagged by what polypeptide?
What are the 3 enzymes called that work together to tag proteins for degradation?
E1, E2, and E3 ubiquitin conjugating enzymes.
Where is the major site of amino acid degradation in mammals?
The major site is the liver
What do aminotransferases do?
They function as dimers and are enzymes that transfer the amino group from amino acids to keto acids.
What does glutamate dehydrogenase do?
It uses oxidative deamination to produce NH4+ and alpha-ketoglutarate from glutamate.
WHat does the combined activity of aminotransferases and glutamate dehydrogenase result in?
It results in the deamination of amino acids to produce NH4+.
What is the net reaction of aminotransferases and glutamate dehydrogenase?
Alpha-amino acid + NAD+ + H2O <----> alpha-keto acid + NH4+ + NADH + H+
Where are the two places the urea cycle takes place?
It takes place in the mitochondrial matrix as well as the cytosol.
What is the net reaction for urea synthesis?
CO2 + NH4+ + 3 ATP + aspartate + 2 H2O ----> urea + 2 ADP + 2 Pi + AMP + PPi + fumarate
What intermediate links the urea cycle directly to the citric acid cycle?
Hyperammonemia is due to what?
It is due to the build-up of glutamine which can cause osmotic effects that lead directly to brain swelling.
What can treat argininosuccinase deficiency?
Arginine treats it.
Phenylalanine is hydroxylated by what to form tyrosine?
It is hydroxylated by phenylalanine hydroxylase
What does a genetic deficiency in phenylalanine hydroxylase lead to?
It leads to phenylketonuria (PKU) resulting in severe mental retardation.