Carbohydrate Metabolism

Digestion and Absorption of Dietary Carbohydrates

Starch and glycogen are hydrolyzed by alpha-amylase present in

saliva and pancreatic juice.
Sucrose is hydrolyzed to glucose and fructose.
D-glucose and D-galactose is taken up by Na dependent
cotransport and D-fructose is taken up by Na independent
transport.
Intestinal epithelial cells use glutamine as an energy source to
spare glucose.
The first major tissue to remove glucose from the blood are
parenchymal cells of the liver.
When glucose levels are high in the blood, the liver metabolizes
glucose to pyruvate by glycolysis or synthesize glycogen by
glycogenesis.
When glucose levels are low in the blood, the liver breaks down
glycogen by glycogenolysis to yield glucose.
When glycogen stores are depleted, the liver synthesizes glucose
by gluconeogenesis from non-carbohydrate precursors.
The blood glucose levels are regulated by glucagon and insulin
from pancreatic cells.

Glucose Uptake and Metabolism

Glucose Transporters All GLUT transporters except GLUT 4 are

present in the cell membrane.
1. GLUT 1- RBC and brain cells.
2. GLUT 2 Intestine, kindeys, liver and pancreas.
3. GLUT 3 brain, kidney, placenta
4. GLUT 4 Muscle, heart, adipose. GLUT 4 exist in vesicles in
the absence of insulin and is translocated to the membrane
when insulin is present. Expression of insulin receptors
increases in response to hypoxia or exercise.
5. GLUT 5 Muscle, spermatozoa.
In type I diabetes, lack of insulin prevents translocation of GLUT 4
to cell membrane and contribute to hyperglycemia.
Uptake of glucose in RBC, brain and liver does not require insulin.
Uptake of glucose in adipose, muscle, heart require insulin.

Metabolic Fate of Glucose

RBC Lack mitochondria, glucose metabolized to lactic acid,

pentose phosphate pathway (PPP) yield NADPH.

Brain Pyruvate from glycolysis, NADPH from PPP, and ATP for
ox-phos.
Muscle and Heart Pyruvate and lactate from glycolysis, NADPH
from PPP, ATP from ox-phos, glycogen from glycogenesis.
Adipose Tissue Glycolysis to produce pyruvate that is converted
to acetyl-CoA, NADPH from PPP, glycogen from glycogenesis.
Liver Pyruvate and lactate from glycolysis, NADPH from PPP,
Acetyl-CoA, Glycogenesis, Gluconeogenesis, and drug detox

Regulation of Glycolytic Pathway

Hexokinase

Present in most tissues in the body.

Low Km for glucose; high affinity.
Inhibited by glucose-6-phosphate.
Low Km is useful for brain, it can utilize glucose even in low conc.

Glucokinase

An isoenzyme of hexokinase, present only in liver.

High Km for glucose.
Converts glucose to glucose-6-phosphate.
The liver only uses glucose when glucose levels are high.
Insulin upregulates glucokinase.
Type 1 diabetes patients cannot upregulate glucokinase due to a
lack on insulin. Result in hyperglycemia.

Phosphofructokinase-1

Converts G-6-P to fructose-1,6 bisphosphate.

Regulated by negative allosteric inhibitors: ATP, citrate, and low
pH.
Regulated by positive allosteric inhibitors: AMP and F-2,6
bisphosphate.
Most tissues prefer to use fatty acids and ketone bodies to
produce ATP. Citrate presence means that theres no need to
breakdown glucose.
High levels of anaerobic glycolysis produce lactic acid and H+.
Lactic acidosis can be the result of strenuous exercise and
hypoxia.
Vasodilators to increase circulation and bicarbonate can alleviate
acidosis.

Phosphofructokinase-2

PFK2 converts F-6-P to F-2,6 BP.

F-2,6 BP is a positive allosteric activator for PFK1
Low glucose release of glucagon activate adenylate cyclase
increase cAMP cAMP binding to protein kinase (R2C2)
releases catalytic subunits (C2) catalytic subunits
phosphorylate PFK2 PFK2 inhibited glycolysis inhibited.
High glucose insulin released activation of phosphatase
PFK2 dephosphorylated PFK2 activated glycolysis proceeds.

Pyruvate Kinase

Convert phosphoenol pyruvate to pyruvate.

Glucagon release activate adenylate cyclase increase cAMP
phosphorylation of pyruvate kinase inactivation of pyruvate
kinase glycolysis inhibited.
Patients with deficiency of pyruvate kinase have high levels of
phosphorylated phosphoenol pyruvate and low intracellular ATP.
RBC undergoes hemolysis and result in hemolytic anemia.