How do cells couple ATP hydrolysis to work?
mechanical work - protein changes conformation
transport work - transfer of phosphate changes conformation for transport of molecules across membranes
biochemical work - coupling favorable to unfavorable reactions, creation of activated intermediates
the property of a sytem that regulates its internal environment and tends to maintain a stable, constant condtion of properties
Name the three homeostatic mechanisms.
1. receptor that senses a stimulus
2. control center (integrator) that determines the response to the stimulus
3. effector that carries out instructions from the control center using positive or negative feedback mechanisms
Are most sugars in the body D or L sugars?
opening and closing of the carbohydrate ring that allows changes in the position of the hydroxyl attached to the anomeric carbon
formed by reduction of the aldehyde in an aldose sugar, all of the carbons contain hydroxyl groups
Name the major dietary carbohydrates and their subcompnents.
Maltose - glucose 1-4 glucose
Lactose - galatose 1-4 glucose
Sucrose - glucose 1-2 fructose
Name the three types of storage sources for glucose.
amylose, amylopectin, and glycogen
branched polymer of glucose linked by 1-4 glycosidic bonds except at branches which are 1-6 bonds, highly branched, degraded by glycogen phosphorylase and debranching enzyme
How does glucose get transported into the cell?
What is the key regulatory step of glycolysis?
phosphorylation of Fructose-6-P to fructose-1,6-bisphosphate, catalyzed by phosphofructokinase-1, thermodynamically and kinetically irreversible
transported into cells by GLUT5
mainly metabolized in the liver
benign condition due to absence of fructokinase, fructose is excreted in the urine
hereditary fructose intolerance
due to absence of aldolase B, leading to accumulation of fructose 1-phosphate
also known as Leloir Pathway, converted to glucose to enter glycolysis
classical and non-classical galactosemia
classical - GALT deficiency, build up of galactose-1-P, can lead to neurological damage
non-classical - GALE deficiency, galactose excreted in urine
Describe the different regulatory mechanisms in glycolysis
regulation by ATP/ADP/AMP and cintrate levels
levels of product and substrate regulate PFK-1 and PFK-2
glucokinase in liver regulated byby nuclear mechanism GKRP
NADH is reoxidized in the cytosol by lactate dehydrogenase by the reduction of pyruvate to lactate
erythrocyte pyruvate kinase deficiency
high rate of glycolysis in malignant tumor cells, need for ATP and ribose-5-phosphate, many times these cells experience anaerobic conditions in tumors
metabolism of sugar alcohols
in hyperglycemic conditions, excess sorbitol can cause tissue damage due to osmotic effects
fatty acid oxidation
major source of energy between meals and during increased demand
during fasting, provides ketone bodies as fuel for many tissues
higher energy yield per mole than glucose
occurs primarily in the mitochondrial matrix
activation and transport of fatty acids
uses carnitine to transfer fatty acids into the mitochondrial matrix, several important transfer proteins are used such as carnitine palmitoyl transferase I (CPTI)
Describe the beta-oxidation process of long chain fatty acids
shortened 2 carbons at a time by a series of 4 reactions
general process - oxidation, hydration, oxidation, cleavage
regulation of beta oxidation
blocked at high levels of reduced factors
oxidation pathways turn off malonyl-CoA
oxygen and a functioning ETC is required
oxidation of odd chain fatty acids
undergo beta-oxidation until a 3 carbon propionyl CoA, which is converted to succinyl CoA for the TCA cycle
energy yield for beta-oxidation
1 mole of palmitate (C16) leads to 28 moles of ATP from the 7 FADH2 and 7NADH molecules generated, 2 moles were consumed for activation
very long chian fatty acid oxidation
usually for more than 22 carbons, undergoes alpha and beta oxidation in the peroxisome
first step produces hydrogen peroxide
acetyl-CoA molecules and short acyl-CoAs are derivatized with carnitine and diffuse from peroxisomes to be taken up by mitochondria and fully oxidized
carried out in the ER
omega methyl group is oxidized to an alcohol and then turned into a carboxylic acid
the resulting dicarboxylic acids are oxidzed by beta-oxidation to compounds that are 6-10 carbons long
released in the blood and then oxidized or excreted in urine (usually indicating failure of beta-oxidation pathways)
oxidation fo ketone bodies
oxidation of beta-hydroxybutyrate and acetoacetate, the first is more reduced and provides more energy
done in mitochondrial matrix, often used in starvation conditions
disorders of fatty acid oxidation
carnitine deficiency or defect in carnitine transferase or translocase
hyperketotic hypoglycemia - caused by medium chain fatty acyl CoA dehydrogenase deficiency
dicarboxylic aciduria - consequence of omega oxidation when beta oxidation is impaired
Zellweger syndrome - defect in peroxisome biogenesis, cannot oxidize very long chain fatty acids
pyruvate dehydrogenase complex (PDC)
lniks glycolysis to TCA cycle by oxidizing pyruvate to acetyl CoA, mitochondiral large multi-subunit enzyme complex with three functional proteins
reaction uses oxidation to liberate CO2 from pyruvate - called oxidative decarboxylation
Name the three subunits of PDC and their functions.
pyruvate dehydrogenase (E1) - uses thiamine pyrophosphate as a cofactor, catalyzes the decarboxylation step and transfers acetyl group to lipoate cofactor of E2
dihydrolipoyl transacetylase (E2) - uses lipoate and CoA to transfer acetate to CoA
dihydrolipoyl dehydrogenase (E3) - uses FAD and NAD to re-oxidize the lipoate cofactor of E2
regulation of pyruvate dehydrogenase
ATP/ADP, NADH/HAD+, and acetyl-CoA/CoA ratios are the main regulators
phosphatase and kinase activate and deactivate the complex
during starvation there is high kinase, which prevents glycolysis from preceding, turning to fat and muscle oxidation
Describe and recite the tricarboxylic acid cycle.
accounts for 2/3 of ATP production from fuel oxidation
utilizes acetyl CoA from glucose, fatty acids, amino acids, and keton bodies
occurs in the mitochondrial matrix
activity tightly cooridnated with rate of electron transport chain and oxidative phosphorylation by feedback regulation reflecting the demand for ATP
What are the steps that are largely negative in the TCA cycle?
citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase
What are the important positive free energy steps of the TCA cycle?
malate dehydrogenase and aconitase
Deficienccies of what three enzymes in the TCA are more commonly found in diseases?
fumarase, succinate dehydrogenase, and alpha-ketoglutarate dehydrogenase
a drug that inhibits acetaldehyde dehydrogenase, makes person sick after alcohol, negative stimulus for drinking