Carbohydrates and Sugars Flashcards
What is the definition of metabolism?
A sum of enzyme catalyzed reactions by which a living cell perpetuates and replicates itself.
Define intermediary / energy metabolism
Set of reaction concerned with generation or storing energy and using that energy for biosynthesis of small molecules. In other words it is associated with maintenance of cellular ATP & blood glucose levels.
Describe anabolic pathways
Biosynthesis pathways that use energy derived from catabolic pathways. Ex: Gluconeogenesis and glycogenesis
Describe Catabolic pathways
Oxidative breakdown of complex larger molecules that result in energy release captured by formation of ATP. This can be described as an exergonic process. Examples are glycogenolysis and glycolysis.
What is the term for a metabolic pathway that can be both catabolic and anabolic? What pathway would this be?
Amphibolic; Citric acid cycle
What can be accomplished removing H+ from a carbohydrate in a stepwise fashion? What other things are needed?
Energy release; enzymes, and electron/protein acceptors such as NAD+ or FAD+
NADPH or NADH loses a hydrogen this is an example of?
Oxidation
NAD+ or NADP+ gains a hydrogen this is an example of?
Reduction
Give two examples of proton / hydrogen acceptors.
NAD+ and NADP+
What are three monosaccharides?
fructose, galactose, and glucose
Name three disaccharides.
Sucrose, lactose, and maltose
What is the suffix in a name for sugars?
-ose
Monosaccharides are _______.
D - stereoisomers in humans.
What are the two different ring structures?
Pyranose - 6 carbon ring. Furanose - 5 carbon ring.
What group and which carbon / position can be adapted to be in alpha or beta conformation?
The OH - group at position one.
What conformation is most stable for glucose?
Beta conformation
What conformation is most stable for polysaccharides such as starch and glycogen?
Alpha conformation.
What is the term to describe a sugar that has 2 to 10 monosaccharides per unit?
Oligosaccharide
What is the term to describe a sugar that has greater than 10 monosaccharides per unit?
Polysaccharides such as cellulose, starch, glycogen, and glucan (polysaccharide of D - glucose monomers)
What sugar is responsible for 80% of monosaccharides in a person’s diet?
Starch (polysaccharide)
What minor carbs are in a person’s diet?
Glycogen, alcohol, lactic acid, pectin & dextran
Where does digestion start for sugars?
In the mouth where amylase is secreted. Amylase hydrolyzes starch into maltose and other small polymers of glucose.
What inhibits amylase activity as carbs make its way through the body?
Gastric secretions inhibit amylase activity after about an hour in digestion.
What is another source of amylase in the body?
Amylase is secreted from the pancreas when chyme enters the duodenum.
What needs to happen to disaccharides and oligosaccharides before they are absorbed?
They need to be broken down to monomers
What are the four enzymes located in brush border of cells?
Lactase, sucrase, maltase, & alpha - dextrinase.
Where do monosaccharides go after being absorbed?
To the portal blood
Which glucose transporter has a low affinity to glucose?
GLUT - 2 found in areas of high glucose concentration such as small intestines, renal tubules & liver.
If a glucose transporter has a high affinity to glucose would the Km value be high or low?
Low Km value
If the glucose transporter has a low affinity to glucose would the Km value be high or low?
High Km
Define Km for enzyme kinetics
The concentration of substrate which permits the enzyme to achieve half Vmax (reaction rate when the enzyme is fully saturated by substrate)
Which glucose transporter has a high affinity to glucose?
GLUT - 1 and GLUT - 3 in glucose sensitive tissue such as the brain and RBCs
Which glucose transporter has an intermediate affinity to glucose?
GLUT - 4 in insulin dependent muscle & adipose cells
What is the purpose of glycogen?
Storage form of glucose in muscles and liver. Another name for it is polymeric glucose
What is the purpose of monosaccharides?
Its the major source of energy and primary form of nutrition.
What kind of substance does the brain use to fuel brain activity?
Glucose
What can glucose be converted into besides energy for the body?
Ribose, or turned into oxidized / reduced form such as mannitol or glucuronic acid
What are the components of synovial fluid and connective tissue?
Long chains of hyaluronic acid and keratin sulfate.
How do monosaccharides turned into energy?
They are phosphorylated. Depending where the phosphate group is added will decide where they enter glycolysis pathway. Galactose is phosphorylated to G-1-P, Glucose is phosphorylated to G-6-P, and Fructose is phosphorylated to F-6-P or F-1-P.
Where is fructose primarily metabolized?
Liver, kidney, and small intestine
In the liver, what enzyme is responsible for adding a phosphate group to position one (1st carbon)?
Fructokinase
What enzyme is responsible for adding a phosphate group to the sixth position (6th carbon)?
Hexokinase, you get F-6-P
what is the disorder that describes the liver is deficient for fructokinase?
Essential fructosuria. Another name that describes it is false diabetes mellitus.
Fructose - 1 - P adolase is deficient in the liver, kidney cortex, and small intestine. What is this condition called?
Hereditary fructose intolerance
A patient has hereditary fructose - 1,6 - bisphosphatase deficiency is glycolysis affected?
No
What needs to happen for galactose to enter glycolysis?
Galactose needs to be phosphorylated by galactokinase to make Galactose - 1 - phosphate. Then Gal-1-P needs to be epimerized to Glucose-1-P by UDP-Glc-Gal-1-P uridylyltransferase. The last step before entering glycolysis is moving the phosphate group with the help of phosphoglucomutase.
The body is deficient in uridylyltransferase (GALT) what condition describes this disorder?
Classic galactosemia (leads to lactose intolerance)
A disorder that is due to the loss of galactokinase (GALK) and what are the consequences?
Galactosemia; lactose intolerant, and may lead to blindness and fatal liver damage.
What organ controls blood glucose levels?
The liver.
What ways does the liver have to increase glucose levels?
Draw on glycogen levels, convert intestinally absorbed galactose & fructose to glucose, and produce glucose through the gluconeogenesis pathway (G-6-phosphatase activity).
What organ produces important glucose metabolites and what are they?
Liver; Ribose & oxidizes / reduces to form complex monosaccharides
What is gluconeogenesis?
Process that produces glucose-6-phosphate from amino acids, fatty acids, glycerol, and lactate. Gluconeogenesis is an anabolic pathway that forms glucose from non-carbohydrate substances.
What is glycogenolysis?
a process by which glycogen is broken down into glucose.
What is glycolysis?
The catabolic pathway that breaks down monosaccharides to produce 2 pyruvate molecules, 2 ATP, and 2 NADH.
What is glyconeogenesis?
Produces the storage form of glucose. It occurs in the cytoplasm in liver and muscle cells.
What is the hexose monophosphate shunt?
????
Describe glycogen
A high molecular weight polysaccharide composed of glucose. Its linked with alpha (1 to 4) glycosidic bonds & branches with alpha (1 to 6) glycosidic bonds every 10 units.
What are the three steps of glycogenesis?
- Step #1: glucose-6-phosphate is catalyzed by phosphoglucomutase to glucose-1-phosphate
- Step #2: glucose is activated with UTP which is catalyzed by UDP-glucose pyrophosporylase to UDP-glucose
- Step #3: glycogen synthase adds UDP-glucose to growing glycogen molecule.
Glycogen synthase (GS) is inhibited by what?
PKA phosphorylation
What hormones increase cAMP? What other effect will this have on glycogen synthase?
Glucagon & epinephrine; inhibit glycogen synthase
Glycogen synthase activity is increased if what chemical group is removed?
Phosphate
What condition would prompt insulin - regulated phosphatase to remove a phosphate group from glycogen synthase?
Decreasing cAMP concentrations
Branching enzyme attaches what molecule(s) to glycogen?
Attaches 5 - 6 glucose units to glycogen via alpha (1 - > 6) glycosidic bonds
What does glycogen phosphorylase do?
Cleaves glycogen to glucose - 1 - phosphate
What enhances glycogen phosphorylase activity?
PKA activating phosphorylase kinase
What hormones increase cAMP? Increas
?????
What does phosphoglucomutase do?
convert glucose - 1 - phosphate into glucose - 6 - phosphate
Liver glucose - 6 - phosphatase does what?
Removes phosphate from g-6-p to allow it to diffuse from liver into circulation
Is glycolysis functional under anaerobic conditions?
Yes
What organelle are cells missing that they cannot function aerobically? Where can they be found?
Lack mitochondria; RBCs, Lenz & retina slide 33
Where does glycolysis take place?
In the cytosol of cells
What does the first step of glycolysis do to glucose?
Its irreversible. It traps glucose in the cell by adding a negative charge to glucose (phosphate group), conserves metabolic energy, and phosphate group lowers activation energy.
What is the enzyme that catalyzes the first step of glycolysis in liver cells?
Glucokinase
What is the enzyme that catalyzes the first step of glycolysis in muscle or fat cells?
Hexokinase
Glucokinase is inhibited by what?
Fructose-6-phosphate
What triggers/induces glucokinase activity?
Insulin
Hexokinase is inhibited by what?
Glucose - 6 - phosphate not fructose-6-phosphate
What are the enzymes of glycolysis that can be regulated?
Hexokinase/glucokinase, phosphofructokinase-1 (PFK-1), and pyruvate kinase
Glyceraldehyde 3 - phosphate dehydrogenase uses NAD+. How is it replenished under anaerobic conditions?
Conversion of pyruvate to lactate by LDH regenerates more NAD+ for glyceraldehde - 3 - phosphate dehydrogenase to work
Glyceraldehyde 3 - phosphate dehydrogenase uses NAD+. How is it replenished under aerobic conditions?
Theres a shuttle that passes H+ to FAD+ (turning into FADH2). choo choo
Glyceraldehyde 3 - phosphate dehydrogenase uses NAD+. How is it replenished under aerobic conditions in the heart and skeletal muscle?
Hydrogen ions are given to NAD+ (turning into NADH) then eventually transferred to malate to transport within mitochondria.
What reagents are used by glucose - 6 - phosphatase in gluconeogenesis?
Amino acid, Fatty acid, glycerol, and lactate.
– Lactate goes pyruvate,
– Alanine goes to pyruvate,
– Glycerol goes to glyceraldehyde-3-phosphate (Primary precursors for glucose synthesis?)
Gluconeogenesis takes place where?
Liver and kidneys
Pentose Phosphate Pathway produces what?
Ribose
Describe Pentose Phosphate Pathway.
Produces ribose with oxidative & non-oxidative steps. Pathway produces NADPH which is important for biosynthetic processes. Ribose used to produce nucleotides and nucleic acid.
Where does pentose phosphate pathway take place?
- Active in FA & steroid synthesis: adrenal gland, liver, adipose tissue &
mammary gland - RBCs: Maintain their membrane integrity.
- Rapidly dividing cells: require DNA synthesis
What are the byproducts of the first step in the pentose phosphate pathway? Hint: Glucose-6-phosphate dehydrogenase
NADPH and 6-phosphogluconolactone.
What is the byproduct of the second step in Pentose phosphate Pathway?
H+ ion; 6-phosphogluconolactone is hydrolyzed in this step.
What is the byproduct of the third step in pentose phosphate pathway?
NADPH, CO2, and ribulose - 5 - phosphate. oxidative decarboxylation occurs by 6-phosphogluonate dehydrogenase
An enzyme is an isomerase, what will happen to the reactant?
?????
What is the fate of hexose phosphates in the pentose phosphate pathway?
They are recycled through the pentose phosphate pathway or go through glycolysis.
What organs and glands are involved in the regulation of carbohydrates?
Pancreas, adrenal gland, thyroid, and pituitary
Where is insulin synthesized?
Beta cells of the pancreas as proinsulin
What stimulates the release of insulin from the beta cells?
Neural, dietary (glucose, and amino acids which increase gastric inhibitory peptide that increase insulin), or hormonal stimulation (GIP, somatostatin, and bombesin)
What organs are targeted by insulin?
- Liver which decreases proteolysis, lipolysis, gluconeogenesis, and
glycogenolysis - Muscle which increase protein synthesis
- Fat which increases triglyceride synthesis
Where is glucagon produced?
Islet of langerhans alpha cells of pancreas
What triggers the synthesis of glucagon (storage of glucose)?
High glucose concentration in blood
What triggers the degradation of glucagon?
Increase amino acids and exercising (need energy for the body)
What increases glucagon levels?
– glycogenolysis: activates PKA & phosphorylase kinase
– gluconeogenesis,
– ketogenesis by inhibiting storage of TG in liver (fat increases lipolysis)
Somatostatin is synthesized where?
islets of langerhans delta cells of pancreas
What triggers the release of somatostatin?
Low blood glucose level (stimulates degradation of glucagon). There is glucagon stimulate somatostatin and is triggered when there is high blood glucose level.
What does somatostatin do?
Acts locally to decrease insulin & glucagon secretion
* The effect is to increase for a period of time which nutrients are
assimilated into the bloodstream
Where is cortisol released from?
Adrenal cortex
What regulates cortisol?
ACTH, Adrenocorticotropic Hormone
What does cortisol do to the body?
Increase blood glucose level by increasing gluconeogenesis activity in liver, increase enzymes in gluconeogenesis, and mobilize amino acids from hepatic tissue
What stimulates the release of epinephrine?
stimulation of sympathetic nerves to the adrenal medulla.
What are the effects of epinephrine to the body?
Results in # [glucose]blood due to:
* Decrease insulin secretion
* Increase Glucagon secretion
– Increase in glycogenolysis
– Increase in gluconeogenesis
Where is thyroxine released from?
Thyroid gland
What are the effects of thyroxine (T4) to the body?
- Results in an overall increase in protein synthesis
- Increase in glucose uptake
- Increase in glycolysis
- Increase gluconeogenesis
Increase rate of glucose absorption from intestinal tract
– Also results in increased insulin but a secondary to increasing
blood glucose
What hormone is responsible for causing growth in all tissue (only ones that can grow)?
Growth hormones
What hormone counteracts “in general” the effects of insulin on glucose & lipid metabolism?
Growth Hormone
What is the effect of growth hormones on the body?
Results in overall increase blood glucose as results:
* Decrease utilization glucose for energy
* Increase in glycogen deposition in cells
* Decrease uptake of glucose by cells that leads to increase blood glucose
A patient is fasting, his blood’s glucagon levels increase, insulin decreases, and cAMP increases. What is the body’s response to this?
Increase glycogen degradation and decrease glycogen synthesis.
A healthy patient has a platter of spaghetti. His liver’s glucagon levels are low, insulin is high, glucose is high in blood. In the tissue cAMP is low and glucose is high. How does the body respond? In terms of glycogen storage & uses.
Glycogen degradation decreases and glycogen synthesis increases. Tons of energy excellent to store for another day.
A healthy person is exercising. His blood has increase epinephrine. His tissue has increased cAMP and increased Ca2+ - Calmodulin. How does his body respond in terms of glycogen.
Glycogen degradation increases (body needs more energy to fuel muscles). Glycogen synthesis decreases.
A healthy patient is fasting. Muscles have decrease insulin circulating in the blood. How does the body respond in terms of glycogen and glucose?
Glucose transport decreases and glycogen synthesis decreases.
A healthy patient ate a ton of pasta. The muscle’s blood insulin levels are high. How does the body respond in terms of glucose and glycogen?
Glucose transport increases and glycogen synthesis increases.
A patient is doing Pilates. Their muscle’s epinephrine levels in blood are increased. Tissue has increased AMP and Ca2+ calmodulin increased
Glycogen synthesis decreases, glycogen degradation increases, and glycolysis increases.
What are three sources Acetyl - CoA can come from?
Glycogen -> Glycogenolysis ->Glycolysis-> Oxidation
Triglyceride -> Lipolysis -> Beta oxidation
Protein -> Proteolysis -> Deamination and oxidation
What is oxidative decarboxylation? What is so important about it?
The reaction involves oxidation - reduction & decarboxylation. It is important because It turns NAD+ into NADH. Thiamine pyrophosphate always participates in the reaction. The chemical is irreversible in other words, no take backs.
How is PDH, Pyruvate dehydrogenase (complex) regulated by inhibited (allosteric means)?
Inhibited by ATP, Acetyl - CoA, and NADH
How is PDH, pyruvate dehydrogenase complex activated allosterically?
Activated by AMP, CoA and NAD+
How is PDH covalently activated?
Dephosphorylation [ PD phosphatase activity]
How is PDH covalently inhibited?
Inhibited by phosphorylation of E1 (pyruvate dehydrogenase by PD Kinase activity by ATP)
What are key sites of regulation of the TCA?
- Citrate synthase
- Isocitrate Dehydrogenase
- Alpha - Ketoglutarate dehydrogenase
What inhibits the enzyme citrate synthase in the TCA?
ATP, citrate, NADH, and succinyl - CoA
What inhibits isocitrate dehydrogenase in the TCA cycle?
ATP, Alpha - ketoglutarate, and NADH
What enzymes would be required for pyruvate to avoid being decarboxylation?
Magic enzyme and pyruvate carboxylase
What activates / enhances pyruvate carboxylase activity?
Acetyl - CoA and Biotin (a form of vitamin)
Pyruvate is turned into what if the enzyme is Malic enzyme?
Pyruvate to Malate. Chemical reaction available in prokaryotes and eukaryotes.
Phosphoenolpyruvate carboxykinase is found in what tissue?
Heart and skeletal muscle
What makes glycolysis exergonic?
He Okinawa, Glucokinase, PFK - 1, and pyruvate kinase reactions
How does glycolysis get around the irreversible reactions in its cycle?
It gets a new set of reactions (exergonic) to go in the opposite direction.
What are the substrates for gluconeogenesis?
Lactate (pyruvate) - Cori cycle (RBC Metab. & Muscles working)
Glucose is Amino acids (all but leu & lysine)
Glycerol - TG brokendown
All TCA intermediates
What enzymes are required to convert pyruvate to PEP?
Pyruvate carboxylase and PEPCK (phosphorenolpyruvate carboxykinase)
Conversion of OAA to PEP can occur with what enzyme?
Cytotoxic or mitochondrial PEP CK
What is an important reagent for gluconeogenesis?
NADH and is generated in the cytoskeleton or imported from the mitochondria
True or false, an alcohol generates NADH independent to gluconeogenesis.
True refer to slide 57 for reference
Why is fructose 1,6 isphosphatase important?
It’s a major site of regulation of gluconeogenesis. It bypasses PFK - 1 reaction with a hydrolytic reaction with the enzyme
What is t he major allosteric modulator PFK 1 / Fructose - 1,6 Bisphosphatase couple
Fructose - 2,6 bisphosphate
What would inactivate PFK 1 & activates Fructose -1,6 bisphosphatase?
PFK-2 phosphorylated (inhibited)