Exam 2, Biochemistry

fructose transporter
Muscle and adipose; movement to membrane is controlled by insulin and exercise
RBC and Brain
other extra-hepatic tissues
function of hexokinase
phosphorylates glucose to G6P to trap in in the cell and limit concentration of free glucose
aka Glucokinase, found in liver and beta cells of pancreas; not product inhibited; high Km for glucose
Which steps of the glycolysis pathway are irreversible? What enzymes are involved? What inhibits the enzymes?
Preparation for splitting by PFK 1 (F6P –> F-1, 6P2) AND the final oxidation step by PK (PEP –> PYR);
inhibited by high ATP concentrations
When aldolase catalyzes the splitting of F-1, 6-P2 what are the two products?
DHAP and G-3-P
For every ____ carbons of the initial glucose molecule, there will be a net synthesis of ____ NADH and ____ ATP?
3, 1, 2
How many ATP are netted from the complete glycolytic pathway?
2 ATPs (and 2 NADHs)
What are the two uses for DHAP?
Can be converted to G3P by isomerase OR to accept the reducing equivalents of NADH (so that it can be used for ATP production) by alpha glycerol phosphate dehydrogenase
What is the major enzyme of anaerobic glycolysis, and what does it do?
lactate dehydrogenase; converts pyruvate to lactate by re-oxidizing NADH
What is the role of carnitine and what enzymes are involved in its use?
carriers the fatty acid across the inner mitochondrial membrane; transferase I moves the FA from CoA to carnitine, translocase moves the acyl-carnitine into the matrix, transferase II moves the fatty acid from carnitine back to CoA
Name the products and their quantities resulting from one sequence of beta oxidation?
1 FADH2, 1 NADH, 1 acetyl-CoA, 1 fatty acyl CoA which is two carbons shorter than the initial reactant
Describe the flavoprotein involved in the beta oxidation sequence, its name and function, and why it is important?
fatty acyl-CoA dehydrogenase, a large complex in the inner mitochondrial membrane; the packet energy bound to FADH2 is passed through this complex to CoQ –> III–>cytochrome c –> IV –> OXYGEN to form H2O
What happens to odd chain fatty acids during beta oxidation? What enzymes and coenzymes are involved?
The last three carbons are liberated as propionyl Co-A, which is converted into succinyl CoA. The first enzyme is propionyl-CoA carboxylase bound to biotin; the second enzyme is MM-CoA mutase bound to Ad-B12
What is the difference in the Beta oxidation pathway used for very long chain fatty acids?
1) takes place in the peroxisomes 2) the flavoprotein is a fatty acyl CoA oxidase which reacts directly with molecular oxygen to yield hydrogen peroxide 3) the oxidation stops at the medium chain level and transports the products back to the mitochondria
What is the name of the flavoprotein involved in the TCA cycle and where is it located within the cell?
succinate dehydrogenase, inner mitochondrial membrane; the “missing” Complex II
Name the enzymes of the TCA cycle that are involved in reactions that produce energy
isocitrate, a-KG, succinate, malate, thiokinase
what is the purpose of the alpha glycerol phosphate shuttle and what is the main enzyme involved?
passes reducing equivalents of NADH to DHAP, which becomes alpha glycerol phosphate, crosses the outer mitochondrial membrane, and passes the reducing equivalents to a flavoprotein; the enzyme is alpha glycerol phosphate dehydrogenase
oxidative portion of the HMP shunt pathway
G-6-P to carboxylic acid via 2 hydrogenases; produces NADPH; final product is ribulose phosphate
which pathway converts acetyl CoA into palmitate? what is the rate-limiting enzyme in this process? What is the product after catalyzation by the rate-limiting enzyme?
Fatty Acid synthesis, acetyl CoA carboxylate, malonyl CoA
Which organs have the ability to use active transport to move glucose?
The intestine and the kidney. called sodium-glucose symports, use ATP.
what types of substances must be transported in the blood stream via albumin?
fatty acids, bilirubin, lipid soluble drugs
non-oxidative portion of HMP shunt
takes F-6-P and G-3-P and arranges the carbon backbones to yield ribose phosphate for nucleotide synthesis; freely reversible, may be used as a salvage pathway
ribose phosphate
used for purine and pyrimidine nucleotide synthesis
a backup system that allows the liver to maintain blood glucose for days; catalyzes the synthesis of glucose from lactate, glycerol, and glucogenic amino acids (major source); 2 OAA –> glucose
What process occurs simultaneously with gluconeogenesis?
the urea cycle
alpha cells of pancreas
released in hypoglycemia
receptor in liver and adipose
phosphorylation of enzymes via protein kinase A leads to glycogenolysis, TAG hydrolysis, and gluconeogenesis
inhibited by insulin
insulin to glucagon ratio
increased with increased glucose concentration, activation of regulatory enzymes in metabolic pathways
citrate shuttle system
used in glycolysis; citrate, a product of OAA and acetyl CoA is transported out of the mitochondria and broken down into its components in the cytosol
Ketone bodies
water-soluble lipid fuels that are continuously released from the liver, made only in the liver mitochondria, can be used by the brain when glucose levels are low. Can NOT be used by the liver or RBC.
acetyl CoA –> ketone bodies. The acetyl coA comes from Fatty acid oxidation and is in excess due to OAA being used for gluconeogenesis instead of the TCA cycle.
removes the phosphate group of G-6-P in glycogenolysis, allowing the conversion of glycogen to glucose; only present in liver, kidney, and intestinal cells
excess carbohydrate is converted into triacylglycerol (TAG) in the cytosol of the cell.
phosphofructokinase 1
used in preparation for splitting in glycolysis; phosphorylates the F-6-P at the 1 position, forming F-1, 6-P2, this is the irreversible and controlling step of the glycolysis pathway
G-6-P dehydrogenase
used in the synthesis of the first NADPH from G-6-P in the oxidative portion of the hexose mono phosphate shunt, product is 1 NADPH and lactonase
pyruvate dehydrogenase
a large enzymatic complex used in aerobic glycolysis for the conversion of pyruvate to acetyl CoA
acetyl CoA carboxylase
catalyzes the carboxylation of acetyl CoA resulting in malonyl CoA
pyruvate carboxylase
catalyzes the conversion of pyruvate to OAA, depends on biotin
what enzymes are involved in TAG synthesis?
acyl-CoA transferase and phosphatase
What is the role of citrate in fatty acid synthesis? What enzymes are involved?
Bringing acetyl CoA to the cytosol. Synthase turns Acetyl CoA and OAA into citrate, which crosses the mitochondrial membrane. Lyase turns citrate back into OAA and acetyl CoA
a four carbon dicarboxylic acid that functions as a carrier molecule in the TCA cycle
What is the source of OAA in gluconeogenesis?
The glucogenic amino acids that come from the breakdown of functional body proteins.
Urea cycle
Removes the amino group from the amino acids of the body being used to make OAA for gluconeogenesis. Always occurs simultaneously with gluconeogenesis
glycogen phosphorylase
the key enzyme in the glycogenolysis pathway. Uses phosphoric acid to remove glucose molecules from glycogen as G-1-P. Activated by phosphorylation by PKA.
G6PD deficiency
a genetic deficiency that leads to normocytic, normochromic hemolytic anemia when the individual is exposed to certain drugs (i.e. antimalarial drugs). NADPH levels can not adapt to increased stress due to lack of G6P in oxidative portion of HMP shunt
a consequence of sustained hyperglycemia; glucose is added to an amino group of protein, causing the protein to rearrange and change its function, i.e. the thickening of the basement membrane of kidney tubules
an alcohol needed for cell signaling compounds, inhibited in hyperglycemia, causing pronounced problems with long-bodied nerve cells (i.e. in the legs)
aldose reductase
an enzyme in the lens of the eye that reduces excess glucose to a sorbitol, which is subsequently trapped in the cells, causing an influx of water and cataracts
the product of the glycation of hemoglobin, the best lab value indicator of non-compliance with insulin-dosing in an IDDM patient
hormone sensitive lipase
a key enzyme in hydrolysis of fat stores, present in adipose cells. Activated by phosphorylation. Fatty acids and glycerol are the products of the reaction catalyzed.
acetoacetic acid
a ketone body that at high concentrations, turns into acetone. Accounts for the acetone smell on the breath of a diabetic in metabolic acidosis
1st stage of starvation
glycogenolysis, gluconeogenesis (and urea cycle), lipolysis
2nd stage of starvation
body is living off of fat stores only, length of this stage depends on amount of body fat, fatty acids are used for the muscles heart and liver, ketone bodies are used for the brain (60% brain energy from ketone bodies)
3rd stage of starvation
kidney joins liver in gluconeogenesis; all functional body proteins are eventually broken down, leading to death
glycogen stores
last 2 days
5 major classes of lipoproteins
Chylomicrons (CM), Very Low Density Lipoproteins (VLDL), Intermediate Density Lipoproteins (IDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL)
Functions of lipoproteins
1) FA and TG for energy storage in adipose and energy production in muscle and liver via B-hydrolysis
2) Provide cholesterol for membrane biosynthesis
3) cholesterol for steroid hormone synthesis
4) cholesterol for bile production
5) fat soluble vitamins to liver for storage
6) remove excess membrane building materials for recycling in the liver
molecular aggregates of various lipids and apoproteins
apoprotein functions
1) solubilize lipid components for transport in blood and lymph. 2) direct the secretion of lipid components from their site of synthesis into the circulation 3) direct the clearance or removal of the lipid components from the circulation into tissues for metabolism or excretion
largest and least dense; 98/2 lipid/protein; origin in intestine; dietary delivery of TG,C, and fat-soluble vitamins
second largest, second most dense, 90/10 lipid/protein; origin in liver; denovo FFA and TGs to muscle and adipose
82/18 lipid/protein; origin in circulation; VLDL–> IDL
second smallest and second most-dense; 75/25 lipid/protein; origin in liver/circulation; cholesterol to liver and peripheral tissues
smallest and most dense; 45/55 lipid/protein; liver/intestines; delivers cholesterol from tissues
used in making chylomicrons in the intestinal epithelial cells, an edited version of apoB100
apo C11
present on the CM, VLDL, and HDL, origin in the liver, activates target tissue lipoprotein lipase in the cell membrane of the capillary bed epithelium
coats the lipid droplet of the adipose cell and restricts access, promoting storage
contained in the remnant polar coat of chylomicrons, contributes to the uptake mechanism of dietary cholesterol in the liver
targets HMG-CoA reductase by acting as a competitive inhibitor at the rate-limiting step for cholesterol biosynthesis
steroid response element binding protein; a transcription factor fequired for HMG-CoA reductase expression; activity is decreased with increased cholesterol/cholesterol ester levels
HMG CoA Reductase
the enzyme involved in the rate-limiting step for cholesterol synthesis from acetyl CoA; the target of statins, also inhibited by a negative feedback from the presence of cholesterol
apo B100
found in the polar coat of VLDL and LDL; coordinates the stability of the hydrophobic core
effect of diabetes on LDL
excess glucose can modify LDL, cause apoB100 glycation, blocking internalization and promoting artherosclerosis
can cells degrade cholesterol?
no, that is why it is necessary for LDL delivery to the cell be strictly controlled
Reverse Cholesterol Transport
a mechanism for transferring cholesterol from peripheral tissue back to the liver for disposal; HDL accepts cholesterol
Niemann Pick Type C disease
a genetic disorder in which the sterol binding protein that traffics cholesterol to the plasma membrane of the cell is not functioning; cholesterol accumulates in the endosomes and degradation function of the lysosomes is decreased
ATP binding cassette-apo1 activated; off loads cholesterol and some phospholipids HDL; can be found in both plasma membrane and Golgi
Tangier’s disease
a genetic mutation that causes a disorder of decreased ABCA1, leading to decreased HDL efficiency and increased cholesterol levels in cell membrane; causes orange-ish skin color and increased systemic atherosclerosis disease
lecithin cholesterol acyl transferase; the cholesterol esterification enzyme activated by apoA1
bile salts
made from the cholesterol carried by HDL to the liver; join with cholesterol and phospholipase to form vesicles and are released to bile
a chronic inflammatory disease of the intima of the major blood vessels
oxidation during the atherosclerosis process
the step where LDL infiltrates into the intima and is modified by intimal lipoxygenases released by damaged cells
the scavenger pathway step of the atherosclerosis process
modified apoB100 in oxidized LDL triggers it; the oxidized LDL-modified B100 is picked up by a macrophage, leading to lysosomal degradation in the macrophage and the buildup of C/CE
Foam cells
a macrophage that has built up CE deposits and coalesced; leads to macrophage death and deposit of C/CE left behind to build up in the vessel as plaque
optimal cholesterol levels
LDL less than 100, total cholesterol less than 200, HDL less than 40
Bile Acid Binding Resin drugs
sequester bile salts, blocking readsorption of bile acids, fat micelles, and some dietary fats; causes loose stools and decrease 10-20% in serum cholesterol levels
Nicotinic Acid
inhibits VLDL synthesis in the liver, leading to decrease of LDL; excessive amounts are toxic to the liver
plant sterols
complete block of bile salt, cholesterol, and excess lipid resorption by the intestines
a combined therapy that blocks intestinal cholesterol uptake and inhibits cholesterol biosynthesis in liver. Increases LDL receptors in the liver. A combination of simvastatin and plant sterol
inhibits cholesterol and VLDL biosynthesis in liver; lovastatin + niacin
What is the conjugated form of bilirubin and where is it found in the body? What enzyme/coenzyme is involved in its formation?
bilirubin diglucuronide, in the hepatocytes of the liver, transferase/UDP-glucuronide
where does hemoglobin breakdown occur in the body?
in the macrophages of the spleen
What process is disrupted by lead poisoning? Which enzymes does it disrupt? What is excreted in the urine as an indicator of lead poisoning?
Heme synthesis, 5ALA-DH and ferrochelatase, 5ALA-DH is excreted in the urine because it is not being used
an activated form of R-5-P, used in the denovo synthesis of purine and pyridine nucleotides
dihydrofolate reductase
the catalyzing enzyme of the transition from folic acid to tetrahydrofolate (the coenzyme form of folate); a target of cancer drugs
thymidalate synthase
an enzyme that converts dUMP –> dTMP; dTMP can become dTTP; folate is a key coenzyme in this pathway
a nucleotide necessary for DNA replication; the rate-controller of cell replication
anemia caused by folate deficiency and mechanism involved
macrocytic anemia; lack of dTTP for DNA synthesis = RBCs “stuck” in macrocytic (immature) phase
anemia caused by B12 deficiency
pernicious anema = a macrocytic anemia; usually due to a disorder of intrinsic factor rather than a dietary deficiency of B12
prevents peroxides from forming free radicals in the cell membrane; in the RBC, includes vitamin E, glutathione, superoxide dismutase and catalase
used to catalyze the heme synthesis reaction in which the iron is added to the porphyrin ring
Name some of the necessary components for Heme biosynthesis
glycine, succinyl CoA, ferrochelatase, 5ALA, 5ALA-DH
stores Fe3+ in the cells; presence in the blood indicates cell damage
synthesized in the liver, oxidizes Fe2+ to Fe3+ for addition to transferrin
assists ceruloplasmin with transfer of Fe2+ to transferrin
binds Fe3+ and transports it into the cell, where the entire complex is enveloped by a lysosome; the pH of the lysosome allows the transferrin to release the Fe3+ to ferritin and be transported out of the cell
Name some of the causes of normocytic normochromic anemia
hemorrhage, G6PD deficiency, PK deficiency, sickle cell hemolytic crisis, defect of methemoglobin reductase
what is the primary cause of microcytic hypochromic anemia?
iron deficiency
Name three key folate reactions
serine –> glycine, homocysteine –> methionine, dUMP –> thymidylate (TMP)
glutathione reductase
an NADPH-dependent enzyme that catalyzes the reduction of oxidized glutathione to the reduced form (active form)
protoporphyrin IX
a porphyrin ring that is the main constituent of heme; synthesized from glycine and succinyl CoA
Hemophilia A
deficiency of factor VIII
the extrinsic pathway
initiates the coagulation cascade, tissue factor III + Factor VII
tissue factor III
aka thromboplastin, a transmembrane protein found in the membrane of cells of the sub-endothelium, exposed when vascular damage occurs, binds factor VII to begin extrinsic pathway
aka SPCA, a serine protease that binds to tissue factor III in the extrinsic pathway
intrinsic pathway
HMW-kininogen, pre-kallikrein, calcium, factors VIII, IX, XI, and XII; end result is the activation of Factor IX
Factor XII
activates pre-kallikrein to kallikrein in the intrinsic pathway, becomes activated by kallikrein, XIIa activates XI
activated by XIa in the intrinsic pathway; activates X in common pathway, the deficient factor in Hemophilia type B
Factor X
activated by IXa, activates prothrombin (II) to thrombin (IIa); has maximal activity when co-factored with calcium, Factor Va, and phospholipid
inhibits vitamin K epoxide reductase, leading to a decrease in vitamin K and causes anticoagulation
prothrombin; activated by Xa complex; IIa = thrombin, which hydrolyzes fibrinogen to fibrin
activated by thrombin (IIa), catalyzes the formation of cross-links between fibrin molecules of the soft clot to the hard clot
Factor VIII
the deficiency in Hemophilia type A, activated by thrombin, VIIIa joins the complex that activates Factor X
tissue plasminogen activator; a serine protease found on vascular epithelial cells that breaks down plasminogen to plasmin
the enzyme that degrades fibrin clots
a serine protease inhibitor, activity is enhanced by heparin
an endogenous anticoagulate that activates plasminogen
a protein produced by B-hemolytic stretococcus taht activates plasminogen to plasmin
an integral membrane protein of endothelial cells, binds to thrombin and activates protein C
protein C
an anticoagulant that forms a complex with protein S to degrade Va and VIIIa
vitamin K dependent Factors
von Willibrand factor
a large molecular weight protein found in the circulation and in the platelets, binds to the sub-endothelial proteins and to a platelet receptor, GpIb
which factors are in the complex that activates prothrombin (II) to thrombin (IIa)
Va, Xa, phospholipid of platelet membrane, and calcium
hemoglobin where the oxygen has dissociated, leaving the iron in the Fe3+ form
superoxide dismutase
breaks down the toxic superoxide ion associated with deoxyhemoglobin and converts it to water and molecular oxygen
causes of increased serum bilirubin
G6PD deficiency, blocked common bile duct, deficiency of UDP-glucuronide/transferase, hemolysis

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