Carbohydrate Metabolism Flashcards
Primary Metabolic Pathways to produce ATP
glycolysis, citric acid cycle, oxidative phosphorylation
Main Anabolic pathways to produce new carbohydrate molecules
Gluconeogenesis and Pentose Phosphate Pathway
Purpose of Pentose Phosphate Pathway
To produce sugar rings (Ribose) that are found in DNA and RNA; pathway also produces the most NADPH
Gluconeogenesis
Pyruvate to form glucose
Glycolysis
Glucose 6-phosphate - Triose Phosphate - Pyruvate
Glycogenesis
Glucose 6-phosphate to produce glycogen
Glycogenolysis
Glycogen to produce Glucose 6-phosphate
Catabolism and Anabolism
Catabolism - breakdown and Anabolism (synthesis)
Calculate Calories or Kilocalories
(Enthalpy will be given); energy per gram (kJ/g) = enthalpy/one mole of mass; Kcal (kcal/g) = Energy per gram X (1 kcal/4.18kJ)
Which releases more energy gram for gram, lipids or carbohydrates/glucose? Why?
Lipids release more energy gram for gram compared to glucose/carbohydrates; more bonds to break therefore higher the energy released.
Glycolysis Products
2 Pyruvate + 2 ATP + 2 NADH + 2 H2O + 2 H
Glycolysis Key Regulatory Steps (3)
- Start with Hexokinase OR Glucokinase (Isozymes -
depends on location in body); Glucose to glucose 6-phosphate - Phosphofructo-kinase-1 : fructose-6-P to Fructose-1,6-bisphosphate
- Pyruvate Kinase : Phosphoenolpyruvate to pyruvate
Location of glycolysis and 2 phases
cytoplasm; phosphorylation phase (adding phosphate group) and energy production phase (ATP production)
What will happen to phosphofructo-kinase-1 if you have a high concentration of ATP?
It will inhibit it
How many ATP are formed during Phosphorylation Phase?
Zero ATP produced; you actually use 2 ATP during this phase
Net ATP Produced during Glycolysis phase?
2 ATP
How many ATP are produced during the Energy Production Phase?
4 ATP
What is the role of Magnesium Ion in Adenosine Triphosphate?
Keeps the molecule stable due to the 4 negative charges of Oxygen on the phosphate groups; “peacemaker”
Adenosine Triphosphate Role
primary energy source in the body, but not the only one
Purpose of the phosphate groups in ATP?
high energy bonds between the phosphate groups (phosphoric anhydride bonds); entropy increased; electrostatic repulsion of the positively charged phosphates and negatively charged oxygen stabilized the products (ADP + Pi) of breaking these bonds
What is the role of NADH ? (Nicotinamide Adenine Dinucleotide)
Alternative energy storage
Oxidation and Reduction
Identify any molecule that is oxidized or reduced on test; Oixidation is loss of election and Reduction is gain of election
For example NAD+ is reduced (Gains 2e-) when added to Hydrogen ion to produce NADH
NAD+ added with H+ has a net 2+ charge therefore you need two electrons to cancel the charge making NADH neutral
Glucokinase
Enzyme needed to catalyze glucose to glucose-6-phosphate. Replaces Hexokinase in liver/pancreas
Can only have one of these enzymes for Phosphorylation phase
What happens when energy levels are high? (Relating to Glycolysis)
The glycolytic pathway is inhibited or alternative pathways are promoted for storage of glucose
Other names for the Citric Acid Cycle
Kreb’s Cycle or Tricarboxylic Acid Cycle (T-Acid Cycle)
Where does the Citric Acid Cycle take place?
Mitochondrial Matrix
First step in Citric Acid Cycle and the importance?
Pyruvate enters the citric acid cycle following its conversion to Acetyl-CoA
Pyruvate links glycolysis to citric acid cycle and produces 1 NADH
Products of the Citric Acid Cycle
3 NADH, 1FADH2, 1 GTP and H20
DOES NOT PRODUCE ATP
The total theoretical yield of ATP for the metabolic pathways (glycolysis, oxidative phosphorylation and citric acid cycle)? Actual Yield?
Theoretical Yield = 36 ATP (max limit)
Actual Yield = 30-32 ATP
Most of the ATP is produced during oxidative phosphorylation which takes place in the inner mitochondrial membrane
The CAC removes and converts what to CO2 and makes H2O?
Two Carbons
Very important factor to know about the Citric Acid Cycle (hint hint for test question)
Regulation of the Citric Acid Cycle
Mainly via the [S] for each enzyme as well as inhibition when [P] gets too high
What happens if there is a high level of energy (NADH or FADH2)?
The citric acid cycle is slowed or intermediates are diverted
Role of Acetyl-CoA in the Citric Acid Cycle
2 carbons bond with oxaloacetate (4 carbons) to form citric acid (6 carbons)
Third step that takes place in the inner mitochondrial membrane
Oxidative Phosphorylation
Oxidative Phosphorylation will not take place in the absence of what molecule?
NADH
What happens during “Oxidative” of the Oxidative Phosphorylation phase?
NADH/FADH2 becomes oxidized by transferring electrons to Oxygen, pumping Hydrogen Ions across the membrane and produce Water (respiratory chain)
What happens during “Phosphorylation” in the Oxidative Phosphorylation phase?
Includes both the respiratory chain and ATP synthesis via ATP synthase
Respiratory Chain in oxidative Phosphorylation involves what?
Complexes I-IV and Q protein to transport Hydrogen ion from inside the mitochondria to the intermembrane space between the inner and out membranes
ATP synthase (Complex V)
Enzyme that catalyzes the conversion of ADP to ATP in the presence of inorganic phosphate (Pi)
ADP + Pi ——–>ATP
^ATP synthase
Role of the Complexes (I-IV) and importance of gradient
Electrons to maintain a constant hydrogen ion gradient and this constant hydrogen ion gradient is important to produce water which is critical for the cell to survive
Components of the ATP Synthase
F0 protein: anchors enzyme to inner mitochondrial membrane
Strator: holds the F0 and F1 together
F1 headpiece: produces a conformational change that binds ADP, catalyzes the reaction to form ATP and then releases ATP
How many ATP are produces from 1 NADH and 1 FADH2?
3 ATP per NADH
2 ATP per FADH2
Where does gluconeogenesis take place and when does it occur?
What does gluconeogenesis produce?
Almost exclusively in the liver (little in kidneys)
Occurs when the body has low energy (starvation, long periods of exercise, etc.)
Typically it converts pyruvate to glucose
What other non-carbohydrate carbon substrates can be used to produce glucose in gluconeogenesis?
Lactate, glycerol, and glucogenic amino acids
What enzymes are required in Gluconeogenesis?
Pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase
Will not find these enzymes in glycolysis
Is Gluconeogensis energy efficient?
Absolutely not
Consumes energy (4 ATP, 2 GTP, and 2 NADH)
Does not create energy
Importance of Pentose Phosphate Pathway
Production of ribose rings and NADPH
Two main phases in Pentose Pathway Shunt and what is produced
Phase one (oxidative phase): glucose-6-phosphate is converted to Ribulose-5-phosphate
Products: 2 NADPH, ribulose-5-phosphate and 1 Carbon Dioxide
Second Phase (nonoxidative phase): (FEEDS DIRECTLY INTO GLYCOLYSIS): Ribulose-5-phosphate produces…
Products: ribose-5-phosphate, fructose-6-phosphate, and glyceraldehyde-3-phosphate
Characteristics of Glucose-6-phosphate dyhrogenase deficiency
- abnormally low levels of G6PDH
- most common inherited disease of enzyme deficiency; enzyme can’t synthesize Glucose-6-phosphate therefore the PPP doesn’t work and create NADPH
- PP pathways is the only way that RBCs eliminate reactive oxygen molecules (via NADPH); leads to damage of RBC membrane and cell death if not removed
- Most are asymtomatic; severe patients have liver and kidney problems
- TXT: blood transfer union and/or removal of spleen
- Must avoid many drugs
NADPH (nicotinamide adenine dinucleotide phosphate) Primary Role
Indirectly responsible for eliminating toxic oxygen radicals (highly reactive oxygen molecules); can cause damage to tissues
Where does the Pentose phosphate pathway occur and what does it produce?
Cytoplasm
Produces Pentose carbohydrates for nucleotide synthesis
Glycogen Synthesis (aka Glycogenesis) Steps
Glucose -> Glucose-6-phosphate (catalyzed by hexokinase) -> glucose-1-phosphate + UTP -> UDP glucose + 2 phosphates
Steps to complete Glycogen synthesis
- Glycogen is held together by alpha 1-4 links
- New UDP glucose are added via glycogen synthase
- Glycogen is complete once branching enzyme forms bonds (alpha 1-6 link) every 10 glucose molecules
Glycosyltranferase Inhibitors
Inhibit sugar rings; can be used to treat diabetes
Glycogenolysis Steps
- Repetitive removal of glucose by phosphorylase until four glucose residues are left before the carbons 1 and 6 branch points
- Glucan transferase enzyme removes 3 residue of the branch
- Debranching enzyme cleaves the final alpha 1-6 bond
- Phosphoglucomutase converts glucose-1-phosphate into glucose-6-phosphate (enters glycolysis)
BLUF: cleave glycogen to make glucose when blood sugar is low
Glycogenolysis Inhibitors
Acarbose and miglitol (diabetes treatment): inhibit release of new glucose residues in the small intestine and pancreas
Zanamivir and oseltamivir inhibit cleavage of carbohydrate bonds that allows new influenza particles to be released from an infected cell
Where is the vast majority of glycogen stored?
In the liver but some in the muscles
GSD type 0
Enzyme deficiency, symptoms and TXT
- Glycogen synthase (only liver)
- Fasting decreases sugar, lactate, and alanine as well as increasing ketones and fatty acids. During feeding, increase sugar and lactate - can have muscle cramping
- diet change to avoid increase and decrease blood sugar level (avoid processed carbohydrates)
Cori’s or Forbe’s Disease (GSD type III)
Enzyme deficiency, symptoms and TXT
- Glycogen debranching enzyme
- glycogen accumulation in liver, skeletal muscle and/or heart, leading to associated medical problems. Fasting decreases sugar
- Increase protein diet to promote gluconeogenesis
McArdle’s disease (GSD type V)
Enzyme deficiency, symptoms, TXT
- Muscle glycogen phosphorylase
- inability to perform glycogenolysis -> muscle cramping and breakdown from exercise. Result in kidney failure from muscle breakdown products
- Limited exercise to avoid muscle breakdown. Treatment of kidney disease is required
Eight Carbohydrate molecules in glycoproteins
- Glucose
- Galactose
- Mannose
- Fructose
- Xylose
- N-acetylgalactosamine (GalNac)
- N-acetylglucosamine
- N-actetyneuraminic Acid
Where does glucose come from if a student decided to fast for the last 12 hours?
Glycogen breakdown in liver (hepatic-glycogenolysis
INTEGRATED METABOLISM
What happens if a student goes into starvation? (Longer than 12-24 hours without eating)
Ketone bodies will actually start to feed the brain and body after gluconeogenesis takes place first. Ketone bodies are last resort
Location and function of Mucins (“mucus glycoproteins”)
Location: lungs, saliva, digestive tract, CT
Function: lubrication and protection from bacterial invasion
Increase in cancers and lung disease
Decrease levels may lead to ulcerative colitis
Location and function of Antibodies, major histocompatability complex
Location: white blood cells (immune system)
Function: recognition/activation for various cells of immune system
Location and function of Glycoprotein IIb/IIIa
Location: Platelets
Function: platelet aggregation and clot formation
Deficient or altered: serious bruising/bleeding problems
Biochemical role and function of glycoprotein Hormones
Location: various tissues and functions
Function: FSH, Luteinizing hormone, TSH, HCG, alpha-fetoprotein, erythropoietin
Location and function of Transferin, ceruplasmin
Location: blood
Function: iron and copper transport throughout the body
Location and function of Calnexin and Calreticulin
Location: Endoplasmic reticulum
Function: Ensure proper folding and glycosylation of newly synthesized glycoproteins
Location and function of Notch Glycoproteins (receptors)
Location: nerve, arteries, heart, pancreas, intestines, bone, mam glands and cytoskeleton
Functions: involved in cell development and differentiation in a variety of tissues
Altered: leukemia, multiple sclerosis, tetralogy of fallot, alagille syndrome
Various glycoprotein receptors and membrane molecules location and function
Location: Sperm-egg, virus and bacterial coats, lectins, selectins, hormones, drugs
Function: Involved in cell recognition, attachment and initiation of biological processes via signaling
Anderson’s Disease (GSD type IV)
Glycogen branching enzyme
Accumulation of long and unbranched glycogen molecules in the liver and heart. Leads to failure and death by age 1
Symptomatic treatment and transplant required
