Metabolism -- Normal and Abnormal Carb Metabolism Flashcards
∆G(ATP hyd)
-7.3 Kcal/mol
Define catabolism
Conversion of energy-yielding nutrients into energy-poor end products (larger to smaller molecules, basically)
Define anabolism
Conversion of precursor molecules into complex molecules (smaller to larger, basically)
Components of lactose
Galactase - glucose
Components of maltose
Glucose - glucose
Components of sucrose
Glucose - fructose
Where do disaccharides get digested into monosaccharides?
In gut
Where do monosaccharides become transformed and phosphorylated for further metabolism?
In liver
Phosphorylated product of glucose
Glucose-6-P
Phosphorylated product of fructose
Fructose-1-P
Phosphorylated product of galactose
Glucose-1-P
Metabolic fates of glucose-6-P
Can either:
- Enter glycolysis
- Convert into glucose-1-P for conversion into glycogen
Metabolic fate of fructose-1-P
Glycolysis
Metabolic fate of glucose-1-P
Glycogen
Define lactose intolerance
Deficiency in gene expression for lactase (as we age), causing gut flora to use the lactose instead, creating acid and CO2 in gut –> bloating, cramping and diarrhea
Disaccharide intolerance of Inuits
Sucrose intolerance (10%)
Define type I diabetes mellitus
Autoimmune destruction of insulin-producing beta cells of the pancreas
Define type II diabetes mellitus
Insulin is not sensed is later under produced (“insulin resistance” and deficiency – strongly linked with obesity
Consequence of diabetes mellitus
Glucose and fat homeostasis are deregulated –> hyperglycemia and a very large number of serious health risks
Location of GLUT-2
Liver, pancreas, kidney
Location of GLUT-4
Muscle and adipose tissue
What controls GLUT-4 availability?
Insulin
Input for glycolysis
- 2 ATP
- 1 glucose
Output of glycolysis
- 4 ATP
- 2 NADH
- 2 pyruvate
Net profit from glycolysis
- 2 ATP
- 2 NADH
- 2 pyruvate
What is required to make ATP out of NADH
Oxygen
Location of hexokinase
In tissues other than the liver and pancreas
Hexokinase’s maximal speed and what this means
Moderate = tissues don’t take more glucose than they can use
Location of glucokinase
Liver and pancreas
Glucokinase use in liver
Soak up all the sugar from a meal (high maximal speed)
Glucokinase use in pancreas
Sense glucose levels and control insulin release
What regulated GK transcription in the liver?
+ = insulin
- = glucagon
3 glycolysis enzymes whose transcriptions are regulated by insulin and glucagon
- Glucokinase
- PFK-1
- PK
Drug target for type II diabetes and why
Glucokinase –> up-regulate activity (soak up more sugar and release more insulin)
Condition associated with a single gene mutation in glucokinase
Maturity-Onset Diabetes of the Young (MODY)
Consequence of mutating both genes of glucokinase
Permanent Neonatal Diabetes Mellitus (PNDM)
3 consequences of aldolase B deficiency
- Hypoglycemia
- Secretion of all phosphate –> unable to synthesize ATP
- Fructose bypasses regulation by glucokinase –> Hereditary fructose intolerance
Define the Warburg effect?
- Cancer cells use glucose faster –> lactate instead of acetyl CoA
- Overexpression of hexokinase
- Expression of special variant of pyruvate kinase
Why can lactic acidosis occur?
Lack of oxygen, as seen in:
- Myocardial infarction
- Pulmonary embolism
- Uncontrolled hemorrhage
- Tumor microenvironment
- Muscle overuse/exertion
Enzyme to convert pyruvate to acetyl CoA
Pyruvate dehydrogenase
2 ways that pyruvate dehydrogenase is regulated
- Phosphorylation/dephosphorylation cycle
- Product inhibition
Vitamin required as a cofactor in PDH
Thiamine
Consequence of thiamine deficiency
Lactic acidosis
Consequence of PDH deficiency
Chronic lactic acidosis –> severe neurological defects –> usually lethal
ETC complex that is NOT a proton pump
Complex II
ETC complex that FADH2 enters
Complex II
Effect of cyanide poisoning
Stops ETC by CN- binding Fe3+ in complex IV –> rapid cell death and DNS damage
Effect of CO poisoning
Stop ETC by CO binding Fe2+ in complex IV
Special property of brown fat
Contains proteins in mitochondria that form a channel to allow H+ back into the mitochondria without going through ATP synthase
Enzyme to link glucose molecules together to form glycogen
Glycogen synthase
UDP-glucose + (glucose)n –> (glucose)n+1 + UDP
Activator fro glycogen synthase
Insulin
Inhibitor of glycogen synthase
Glucagon
Purpose of liver in gllucose storage
For later supply of glucose to other tissues in times of fasting
Purpose of muscle in glucose storage
Use as energy source during exercise
Enzyme to remove one glucose link from glycogen
Glycogen phosphorylase
Glycogen chain + Pi –> Glucose 1-P
Enzyme to convert glucose 6-P to Glucose
Glucose 6-phosphatase
Fate of gllucose-6-P in muscle
Glycolysis directly
Fate of glucose-6-phosphate in liver
Conversion into glucose by glucose-6-phosphatase for distribution to other tissues
2 pathologies of glycogenolysis
McArdle Disease
Von Gierke Disease
Enzyme affected bby McArdle disease
Glycogen phosphatase
Enzyme affected by Von Gierke Disease
Glucose-6-Phosphatase
3 irreversible reactions in glycolysis
- Glucose –> Glucose-6-P
- Fructose-6-P –> Fructose 1-6-bisP
- PEP –> pyruvate
4 enzymes to get around glycolysis’ irreversible steps in gluconeogenesis
- Glucose-6-phosphatase
- Fructose-1,6-bisphosphatase
- Pyruvate carboxylase
- PEPC
AEnzyme most tightly regulated to differentiate between the bodies needs for gluconeogenesis vs. glycolysis
Fructose-1,6-bisphosphatase
Activator of fructose-1,6-bisphosphatase
Glucagon
INhibitor of fructose-1,6-bisphosphatase
Insulin
Activator of pyruvate carboxylate
Acetyl-CoA
