Biochemistry Flashcards
In a non-starving state, how is glucose metabolised?
Glycolysis
What is gluconeogenesis?
Synthesis of glucose from pyruvate (end product of glycolysis) Reversal of glycolysis ( uses other enzymes)
What are the steps of glycolysis?
1. Glucose → glucose 6-phosphate (G6P)
Enzyme: Hexokinase: in all tissues (inhibited by G6P)
Glucokinase: in β-cells of the pancreas, and liver tissue (inhibited by fructose 6-phosphate)
Requires ATP
2. G6P → fructose 6-phosphate (F6P)
Enzyme: G6P isomerase
3. F6P → fructose 1,6-biphosphate
Enzyme: PKF-1
Requires ATP
4. Fructose 1,6-biphosphate → glyceraldehyde 3-phosphate (GAP)
Enzyme: aldolase
5. GAP → 1,3-Biphosphoglycerate (1,3-BPG)
Enzyme: GAP dehydrogenase
Produces NADH + H+
1,3-BPG → 3-phosphoglycerate
6. Enzyme: phosphoglycerate kinase
Produces ATP
7. 3-phosphoglycerate → 2-phosphoglycerate
Enzyme: phosphoglycerate mutase
8. 2-phosphoglycerate → phosphoenolpyruvate (PEP)
Enzyme: enolase
9. PEP → pyruvate
Enzyme: pyruvate kinase
Produces ATP
Stimulated by fructose 1,6-biphosphate
Inhibited by ATP and alanine
What is glycolysis? What does it yield?
A metabolic pathway that breaks down glucose by substrate-level phosphorylation and oxidation, yielding 2 pyruvate molecules and 2 ATP.
2 ATP molecules are consumed in this process
What regulates glycolysis?
Hexokinase enzyme:
Role: converts glucose -> G6P
Stimulated by insulin
Inhibited by: G6P formation / glucagon
Phosphofructokinase 1:
Role: Convert F6P -> Fructose 1,6 phosphate
Stimulated by: AMP, Frctuose2,6 phosphate (feed forward mechanism, insulin
Inhibited by: ATP (as energy is plentiful), Citrate (indicated glycolysis intermediates, therefore slows glycolysis), glucagon action in liver
Pyruvate kinase:
Converts PEP to pyruvate
Stimulated by: Fructose 1,5 phosphate (glycolysis intermediate
Inhibited: ATP (indicates plnety of energy), Alanine ( indicates biosynthesis)
What is phosphofuctase 2 and what is its role?
It is a bi-directional enzyme that may act as a phosphatase or a kinase
As a kinase –> it creates fuctose 2,6 phosphate which stimulates glycolysis
As a phosphatase –> stimulates gluconeognesis and reduces glycolysis
What are the phosphatase and kinases domains of phosphofructokinase -2
Phosphatase domain: Fructose-1,6-bisphosphatase
Kinase domain: Phosphofructokinase-1 (PFK-1)
Under what circumstances does phosphofructoasekinase 1 stimulate glycolysis?
Pro-prandial phase
(Acts as a feed forward mechanism)
Postprandial state:
High blood glucose → increased circulating insulin levels (indicate a high abundance of blood glucose available for glycolysis) → decreased levels of cAMP → decreased PKA activity → inhibition of FBPase-2 (phosphatase) and stimulation of PFK-2 domain (kinase)→ increased production of F-2,6-P2 → F-2,6-P2 activates PFK-1→ more glycolysis + less gluconeogenesis
What determines of phosphofructokinase acts as a kinase or phosphatase?
Activity of Protein Kinase A
Post-prandial state: PKA is inhibited by low cAMP
Starving state: PKA activated by high cAMP
Under what circumstances of phosphofructokinase inhibit glycolysis
Fasting State
Fasting state: low blood glucose → increased circulating glucagon levels → increased levels of cAMP → increased protein kinase A (PKA) activity → stimulation of FBPase-2 and inhibition of PFK-2 domain → decreased production of F-2,6-P2 → less glycolysis + more gluconeogenesis
Does glycolysis occur in anaerobic conditions?
Yes
Pyruvate may be used in the kreb cycle or gluconeogenesis
Pyruvate is the final product of glycolysis - which may be converted into lactic acid in anaerobic respiration
How may pyruvate be metabolised?
Lactic acid -> Gluconeogenesis (anaerobic respiration)
Acetyl Co-A -> Krebs cycle (aerobic respiration)
Oxaloacetate -> involved in aerobic and anaerobic resp
Alanine -> Gluconeogenesis
liver converts pyruvate -> alanine via cahill cycle for gluconeogenesis -> produces ammonia (sign of anaerobic resp)
What is gluconeogenesis?
A series of metabolic events that allows for the production of glucose from noncarbohydrate precursors.
When is gluconeogenesis used?
During fasting
After glucogen stores have been used (e.g. 1-3 days after fasting)
What substates can be used for gluconeogenesis?
Amino acids
Lactate (cori cycle)
Fatty acids (e.g. propional Co A)
What is the pentose phosphate pathway?
Alternative metabolic pathway that creates ribose and NADPH from glucose 6 phosphate which may converted into other products
Function of pentose phosphate pathway?
Production of ribose sugar for DNA and RNA
Production of NADPH required for:
- fatty acid synthesis
- cholesterol synthesis
- reduction of glutathione
Where is gluconeogenesis carried out?
Primarily carried out in the liver
Renal cortex
Intestinal epithelium
Skeletal muscle cannot participate in gluconeogenesis due to absent glucose-6-phosphatase
What is a monosaccharide?
A simple carbohydrate that cannot be broken down any further
e.g. glucose, fructose and galatose
What is a disaccharide?
Two mono-saccharides bonded by a glycosidic bond
e.g. sucrose, maltose, lactose
What is a polysaccharide?
Many monosaccharides bonded together?
e.g. starch, glycogen
What are the two forms of glycosidic bond and why is this important?
1,4 - alpha glycosidic bond (OH group below the plane of the ring)
1,4 - beta glycosidic bond (OH group above the plane of the ring)
Lactase is the only enzyme in the body capable of cleaving a 1,4 beta glycosidic bond
What are examples of sugars with a 1,4- beta glycosidic bond?
Lactose
Cellulose
What monosaccharides make up maltose?
Glucose + Glucose
What monosacchardies make up lactose?
Galatose + glucose
What monosaccharides make up sucrose?
Glucose + fructose
How do intestines absorb carbohydrates?
Absorb them as monosaccharides
Therefore: carbohydrates need to be broken down
What enzymes are important for digestion of carbohydrates?
Alpha-amylase: Mouth + Pancreas
Lactase: Intestinal microvilli
Surcase: Interstinal microvilli
Maltase: Intestinal microvilli
How is glucose abosrbed in the body?
- GLUT receptor on cells
- Na+ Glucose transporter in intestinal epithelium and proximal renal tubule
- SGLT1 in intestinal cells
- SGLT2 in proximal renal tubule cells
How is glucose abosrbed in intestinal epithelial cells?
Sodium-dependent glucose cotransporter 1 (SGLT1)
Transporter on the luminal side of mucosa cells
Sodium concentration gradient, which is maintained by basal Na+/K+ ATPase by transporting sodium out of the cell (secondary active transport).
SGLT1 also absorbs galatose
How is glucose absorbed at the kidneys?
Glucose is filtered into the kidneys at the glomerulus and must be reabsorbed
Complete reabsorption in the proximal tubules via 2 types of SGLT → urine normally glucose free
SGLT2: reabsorbs ∼ 98% of urinary glucose in the proximal convoluted tubule (PCT)
One molecule of glucose is absorbed together with one molecule of sodium
SGLT1: reabsorbs the remaining glucose (∼ 2%) as well as galactose in the PST
One molecule of glucose is absorbed together with two molecules of sodium.
Fructose is absorbed via GLUT5 (glucose transporter).
Reabsorption also relies on a sodium concentration gradient via Na+/K+ ATPase.
What is the function of GLUT1 and where is it found?
Location: Most human cells, RBC, CNS, Cornea, Placenta
Function: Allows entry of glucose into cell
What is the function of GLUT2
- Transports all monosaccharide from the basolateral membrane of enterocytes into the blood
- Measures levels of glucose in pancreatic islet Beta cells
- Bidirectional transport of glucose in hepatocytes -> excretion of glucose in gluconeogenesis and takes in glucose for glycolysis
Where is GLUT 2 receptor located?
Hepatocytes
Pancreatic β-islet cells
Kidney
Small intestine
What is the function of GLUT4?
Very important role in glucose metabolism
Insulin stimulates incorportation of GLUT 4 into cell membrane –> allows glucose entry into cell
What is the only insulin dependent GLUT receptor
GLUT4
What is the function of GLUT5?
Fructose transporter
Located: small intestine enterocytes + spermatocytes
