Metabolism Flashcards
Result of one round of fatty acid oxidation/beta oxidation
1 Acetyl-CoA, 1 NADH, 1 FADH2, H+, fatty acyl-CoA that is 2 carbons shorter
Dehydrogenase (1/4 fatty acid oxidation)
Enzyme: dehydrogenase
Occurs between the second and third carbons of fatty acyl-CoA
Products=trans double bond between C-2 and C-3; FADH2
Hydration(2/4 fatty acid oxidation)
Enzyme: hydratase
Water is added to double bond
Products: 3-hydroxy fatty acyl chain
Dehydrogenation (3/4 fatty acid oxidation)
Enzyme: dehydrogenase
Two hydrogens are moved to NAD+
Products: NADH + H+; 3-keto fatty acyl chain
Formation of Acetyl-CoA(4/4 fatty acid oxidation)
Enzyme: thiolase
Bond between C-2 and C-3 is broken/ free CoA is linked to C-3
Products:a Acetyl-CoA and a fatty acyl-CoA chain that is 2 carbons shorter
Rate-limiting step of fatty acid oxidation/beta oxidation
Transport of fatty acid into the mitochondrial matrix via the carnitine shuttle
To make fatty acyl-CoA
Enzyme: acyl-CoA synthase
ATP—> AMP +PP
Creates a high energy thioester linkage
What plasma protein is utilized by fatty acids to be transported into cells?
Albumin
What happens to the products from fatty acid oxidation/beta oxidation?
Acetyl-CoA goes to the CAC
NADH + FADH2 go to the ETC
How many kcal are in 1g of fats?
9 kcal
How many kcal are in 1g of carbohydrates?
4kcal
Energy yield from 1 Acetyl-CoA
10 ATP
Energy yield for 1 NADH
2.5 ATP
Energy yield for 1 FADH2
1.5 ATP
What is the maximum energy yield for glucose oxidation?
32 ATP
Why do lipids have higher energy content?
Fatty acids are more reduced than glucose and when they are oxidized the larger amount of protons released and the result of acetyl-CoA leads to lots of ATP production
Ketone bodies
Synthesized in the LIVER from EXCESS Acetyl-CoA
Exported from the liver to be used as a fuel source
Acetoacetate(non-physiological) and beta-hydroxybutyrate(physiological)
4 carbon molecules/carboxylic acids —> water soluble
Ketoacidosis
High concentration of ketone bodies in the blood
Why are ketone bodies a good source of energy for peripheral tissues?
Soluble in water and don’t need a transport protein
Made in the liver in response to HYPOglycemia
Used routinely in extrahepatic tissues(skeletal/cardiac muscle, intestinal mucosa, and renal cortex
Alternative fuel for brain so that is can spare blood glucose and reduce muscle protein loss during extended fasting
Pathological ketoacidosis
Seen in Type I Diabetes Mellitus
Concentration of ketone bodies in blood(ketonemia) and urine(ketonuria)
Can lead to fruity smell on the breath due to increased production of acetone
Ketogenesis/Ketone Body Synthesis
4 step process to turn excess Acetyl-CoA into ketone bodies
Acetoacetyl-CoA Formation(1/4 ketogenesis)
In: 2 Acetyl-CoA
Enzyme: thiolase
Out: 1 Acetoacetyl-CoA and 1 free CoA
HMG-CoA Formation (2/4 ketogenesis)
In: 1 Acetoacetyl-CoA and 1 Acetyl-CoA
Enzyme: HMG-Synthase(in any cells that makes cholesterol)
Out: hydroxymethylglutaryl-CoA = HMG-CoA and 1 CoA
Acetoacetate Formation (3/4 ketogenesis)
In: HMG-CoA
Enzyme: HMG-CoA Lyase(LIVER ONLY)
Out: Acetoacetate and 1 Acetyl-CoA
Ketone Body Interchange (4/4 ketogenesis)
In: Acetoacetate and NADH
Enzyme: beta-hydroxybutyrate dehydrogenase
Out: beta-hyrdroxybutyrate and NAD+
When is ketone body synthesis favored?
During fatty acid oxidation—> more NADH is present
Ketone Body Utilization/Ketolysis
Ketone bodies go from liver to peripheral cells where they will be converted into acetyl-CoA
Acetoacetyl-CoA Formation(1/2 Ketolysis)
PART 1:
In: beta-hydroxybutyrate and NAD+
Enzyme: betaxhydroxybutyrate dehydrogenase
Out: Acetoacetate and NADH
PART 2:
In: Acetoacetate and succinyl-CoA
Enzyme: transferase
Out: acetoacetyl-CoA and succinate
Acetyl-CoA Formation (2/2 Ketolysis)
In: Acetoacetyl-CoA and free CoA
Enzyme: Thiolase
Out: 2 Acetyl-CoA
Energy yield of ketolysis
Resulting acetyl-CoA goes out to CAC and NADH goes to ETC
Beta-hydroxybutyrate = 21.5 ATP Acetoacetate = 19 ATP
Fatty Acid Biosynthesis
Mostly liver; can occur in adipose
Synthesized in CYTOPLASM
Precursor is Acetyl-CoA—> needs shuttle to get across mitochondrial membrane
Occurs in response to HYPERgylcemic conditions and in response to INSULIN
Acetyl-CoA shuttle
1- acetyl-CoA+oxaloacetate=citrate (citrate synthase)
2- citrate leaves mitochondrial matrix to cytoplasm
3- citrate is cleaved = OAA + acetyl-CoA (ATP-citrate lyase)
4- OAA —> pyruvate (2 step process)
5- pyruvate is transported to mitochondrial matrix
6- pyruvate —> OAA in matrix (pyruvate carboxylase)
Formation of Malonyl-CoA (fatty acid biosynthesis)
Primary regulatory step in fatty acid biosynthesis/rate-limiting ACTIVATED = INSULIN In: Acetyl-CoA and CO2 and ATP Enzyme: acetyl-CoA carboxylase Out: malonyl-CoA and ADP
What is the effect of insulin and glucagon on acetyl-CoA carboxylase?
INSULIN = ACTIVATION
GLUCAGON = INHIBITION
Enzyme: Fatty Acid Synthase (FAS) in fatty acid biosynthesis
Is activated in hyperglycemic conditions where there is an increase of glucose uptake and excess carbohydrates get converted to fatty acids
Addition of 2 carbons from malonyl-CoA to carbonyl end of acyl receptors
Process turns NADPH to NADP+
Out: 16 carbon palmityl-CoA
What are the two essential fatty acids? Why are they essential?
Linoleic acid = omega-6
Alpha-linolenic acid = omega-3
The body cannot make fatty acids with CIS double bonds after position 9
Triacylglycerol Metabolism
Hepatocytes and intestinal epithelial cells
85% of total fuel stores for the body
Transported through blood via lipoproteins
Exported in chylomicrons and VLDL
adipose TAGs are released in response to FASTING
Triacylglycerol
Glycerol backbone
3 fatty acids linked via ester bonds
Fatty Acid Activation
In: TAG
Enzyme: acyl-CoA synthase
Out: fatty acyl-CoA
Glycerol 3-phosphate Production
1- reduction of glycolysis intermediate(dihydroxyacetone phosphate) by NADH
OR
2- phosphorylation of glycerol by ATP
Phosphatidic Acid Formation (lipogenesis 1/3)
In: G3P and 2 acetyl-CoA
Enzyme: acyl-CoA transferase
Out: phosphatidic Acid and 2 CoA
Diacylglycerol Formation (2/3 lipogenesis)
In: phosphatidic Acid and H2O
Enzyme: phosphohydralase
Out: 1,2-diacylglycerol and P
Formation of Triacylglycerol (3/3 lipogenesis)
In: 1,2-diacylglycerol and acetyl-CoA
Enzyme: acyl-CoA transferase
Out: triacylglycerol and CoA
What are the effects of insulin and glucagon on lipolysis?
GLUCAGON = ACTIVATE INSULIN = INHIBIT
Triacylglycerol to Diacylglycerol ( 1/3 lipolysis)
REGULATORY STEP
In: triacylglycerol and H2O
Enzyme: triglyceride lipase/hormone-sensitive lipase —> acts on fatty acid at C-3
Out: diacylglcerol and free fatty acid
Diacylglycerol to Monoacylglycerol (2/3 lipolysis)
In: 1,2-Diacylglycerol and H2O
Enzyme: diglyceride lipase —> acts on C-1
Out: 2-monoacylglycerol and free fatty acid
Monoacylglycerol to Glycerol (3/3 lipolysis)
In: 2-monoglycerol and H2O
Enzyme: monoglyceride lipase
Out: glycerol and free fatty acid
Lipolysis Net Reaction
Triacylglycerol and 3 H2O —> Glycerol and 3 fatty acids
What form is most dietary fat found in?
Triacylglycerols (TAGs)
How much energy is conserved in a biologically useful form? What is it referred to as?
40% Chemical Power
What are the activated precursors(3) that are used to build macromolecules?
UDP-glucose, fatty acyl-CoA, aminoacyl-tRNA
What term is used to describe a metabolic pathway that produces energy and degrades macromolecules?
Catabolic
What term is used to describe metabolic pathways that carry out the activation of precursors and the synthesis of macromolecules?
Anabolic
Catabolism of precursors from lipids, carbohydrates, and proteins produces…?
Acetyl-CoA (to be used in the CAC)
What are the high energy transferring molecules used in the CAC?
NADH and FADH2
The CAC is an aerobic pathway. Where does the oxygen come from?
H2O
What is the difference between citric acid and citrate?
citric acid is protonated
What are the 8 intermediates of the CAC?
citrate and isocitrate(6C)
alpha-ketogluterate(5C)
succinate, furmate, malate, and oxaloacetate(4C)
succinyl-CoA (succinate+CoA)
How many oxidation-reduction reactions are there in the CAC and what enzymes catalyze these?
4, dehydrogenases–> 3 convert NAD+ to NADH and 1 converts FAD to FADH2, two also participate in decarboxylation reactions producing CO2
How much GTP is produced in the CAC?
1 GTP molecule
Where in the cell is the Electron Transport Chain?
Mitochondrial Inner Membrane
What molecules does the Electron Transport Chain/Respiratory Chain accept electrons from?
NADH and FADH2
What makes up the ETC/Respiratory Chain?
four transmembrane complex and a small,mobile, hydrophobic non-protein electron carrier–Ubiquinone Q/coenzyme Q– and a peripheral protein–cytochrome C
NADH donates 2 electrons to which complex?
Complex I
FADH2 donates 2 electrons to which complex?
Complex II
What happens after electrons are donated to Complex I and Complex II?
the electrons are transferred to coenzyme Q which is reduced to QH2–> QH2 will then transfer the electrons to Complex III
What cytochromes are in Complex III?
cytochrome b and cytochrome c1–> sits on the cytoplasmic side of the inner membrane bridging Complex III and Complex IV
What is the function of cytochrome C in the ETC?
It transfers electrons from Complex III to Complex IV
Complex IV, also known as cytochrome oxidase, contains what two cytochromes and what other ion?
cytochrome a and cytochrome a3 and copper ions
Describe how Complex IV transfers electrons.
Complex IV has an O2 binding site where it sequentially transfers electrons through the cytochromes to each oxygen atom (overall 2 protons and 2 electrons are added to each oxygen to make H2O
How is some energy conserved as electrons are transferred from high energy molecules to low energy molecules?
Energy is conserved by the ETC complexes because they pump protons from the matrix to the cytoplasmic side of the inner membrane as they transfer electrons. This created concentration gradient and membrane potential captures about 40% of energy.
What kind of molecule is Complex V?
An ATPase
How does Complex V work?
it is driven by the proton gradient to drive ATP synthesis from ADP and P through a process called oxidative phosphorylation
Why can cytochromes accept and donate electrons?
Heme prosthetic group–> interconverts between the oxidized (Fe3+) and reduced (Fe2+) states.
How many heme groups does each cytochrome contain? What does this mean for electron transport?
1 cytochrome has 1 heme group so it can only transfer 1 electron at a time.
What does aerobic capacity depend on?
density of mitochondria
In what state MUST iron be in on a RBC for proper O2 binding and release?
Reduced/ ferrous/Fe2+
Describe hemoglobin and myoglobin.
H- tetrameric, each subunit possess a heme, can carry up to 4 O2, RBC
M- monomeric, single heme group, the more aerobic the muscle, the higher the concentration of myoglobin
Why do hemes absorb visible light?
due to the conjugated double bonds in the porphyrin ring to which the iron is bound
How much ATP is formed via the oxidation of one Acetyl-CoA to 2 CO2?
10 ATP
3 NADH = 7.5 ATP
1 FADH2 = 1.5 ATP
1 per GTP
PFK1 is allosterically regulated by the adenosine pool. What ACTIVATES PFK1?
ADP and AMP
PFK1 is allosterically regulated by the adenosine pool. What INHIBITS PFK1?
ATP –> don’t need energy produced from glycolysis
Effectors that inhibit enzyme activity are called?
negative effectors
Effectors, that increase enzyme activity are called?
positive effectors
Liver cells maintain a consistently high [ATP]. How does PFK1 overcome this?
Allosteric enzymes usually have MULTIPLE effector molecules. PFK1 has a second effector molecule, fructose 2,6-biphosphate that is produced in response to insulin binding and is degraded in response to glucagon binding.
HYPOglycemia= no F2,6BP is bound, ATP is bound, PFK1 is inhibited
HYPERglycemia= insulin binds to hepatocyte receptors, F2,6BP binds to allosteric site, overcomes ATP inhibition, PFK1 is activated
Reversible phosphorylation, a form of covalent modification of enzymes, will occur on what amino acid side groups?
serine, threonine, and tyrosine –> all have an open OH group
Where does the phosphate group come from in reversible phosphorylation?
ATP
Describe the effect of covalent modification on glycogenesis in hepatocytes during hyper/hypoglycemic conditions.
Enzyme: glycogen synthase
Hyper: insulin, phosphatase, -OH form,GS is ACTIVE
Hypo: glucagon, kinase, -P form, GS is INACTIVE
Describe the effect of covalent modification on glycogenolysis in hepatocytes during hyper/hypoglycemic conditions.
Enzyme: Phosphorylase
Hyper: insulin, -OH form, INACTIVE
Hypo: glucagon, -P form, ACTIVE
What is genetic regulation?
cells can regulate the amount of enzyme present by altering their rates of degradation or synthesis
Give two examples of genetic regulation in response to hyperglycemia (insulin)?
INDUCES glucokinase
REPRESSES glucose 6-phosphatase
Give two examples of genetic regulation in response to hypoglycemia (glucagon)?
INDUCES glucose 6-phosphatase
REPRESSES glucokinase
What metabolic processes will be active in a well-fed liver?
glycolysis, glycogenesis, pentose shunt, fatty acid synthesis, cholesterol synthesis, lipogenesis
What metabolic processes will be active in a well-fed adipose?
glycolysis, pentose shunt, cholesterol synthesis, and to a lesser extent fatty acid synthesis–> most adipose TAGs are imported via VLDL and chylomicrons
What metabolic processes will be active in a well-fed muscle cell?
glycogenesis–> can be anaerobic or aerobic based on presence of O2
Insulin
released from beta cells in the pancreas
released in response to hyperglycemia
ANABOLIC hormone favoring biosynthesis
Is glycolysis in the brain aerobic or anaerobic?
Anaerobic–> glucose is completely oxidized to CO2
What is glucose converted into in RBCs?
lactate
What metabolic processes will be active in a fasting liver cell?
glycogenolysis, gluconeogenesis, fatty acid oxidation
What metabolic processes will be active in a fasting adipose cell?
lipolysis and fatty acid oxidation
What metabolic processes will be active in a fasting muscle cell?
fatty acid oxidation, ketolysis, glycogenolysis–> fatty acids from adipose and ketone bodies from the liver are imported as fuel
NO GLUCAGON RECEPTORS
Early Fasting State = glucagon>insulin–>sub-euglycemic
no food consumption for AT LEAST 4 hours, sufficient hepatic glycogen reserves, decrease in insulin release and increase in glucagon release
Early Fasting State Liver
delivers enough glucose to the blood via glycogenolysis
gluconeogenesis produces a small amount of glucose since demand is minimal
ATP is produced by oxidizing fatty acids sent from adipose TAG reserves
Early Fasting State Adipose
weak glucagon signal will stimulate lipolysis–> provides some fatty acids for tissues like the liver
Early Fasting State Muscle
glycolysis continues to supply ATP, fatty acid oxidation can contribute to some energy production in more aerobic cells
Early Fasting State Brain
glucose is main fuel source–> aerobic glycolysis, CAC, oxidative phosphorylation
Early Fasting State RBC
glucose is ONLY fuel source, energy is produced via anaerobic glycolysis–> converted to lactate and exported
Extended Fasting State
no food consumed for AT LEAST 2 days and NO hepatic glycogen reserves
hypoglycemia/glucagon»>insulin
Extended Fasting State Liver
attempts to maintain glucose homeostasis via gluconeogenesis, no remaining glycogen stores
strong glucagon signal accelerates gluconeoenesis–> precursors consist mainly of amino acids(muscle) and glycerols and lactate(adipose), fatty acids from adipose(lipolysis) are used to make ATP and support ketogenesis releasing ketone bodies to be used as a fuel source
Extended Fasting State Adipose
strong glucagon signal stimulates lipolysis providing large amounts of fatty acids and glycerol from TAG reserves
Extended Fasting State Muscle
ketone bodies are main fuel source for aerobic ATP production, cortisol promotes proteolysis to generate amino acids that are sent to the liver as gluconeogenic precursors
Extended Fasting State Brain
the brain uses both ketone bodies and glucose as fuel for ATP production–> by decreasing its need for glucose muscle protein is spared because the rate of hepatic gluconeogenesis is decreased
Extended Fasting State RBC
glucose is used to make ATP via anaerobic glycolysis–> lactate–> reconverted to glucose by hepatic gluconeogenesis
